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Structural changes in gut microbiome after Ramadan fasting: a pilot study
Abstract
It has been largely accepted that dietary changes have an effect on gut microbial composition. In this pilot study we hypothesised that Ramadan fasting, which can be considered as a type of time-restricted feeding may lead to changes in gut microbial composition and diversity. A total of 9 adult subjects were included in the study. Stool samples were collected before (baseline) and at the end of the Ramadan fasting (after 29 days). Following the construction of an 16S rRNA amplicon library, the V4 region was sequenced using the Illumina Miseq platform. Microbial community analysis was performed using the QIIME program. A total of 27,521 operational taxonomic units (OTUs) with a 97% similarity were determined in all of the samples. Microbial richness was significantly increased after Ramadan according to observed OTU results (P=0.016). No significant difference was found in terms of Shannon index or phylogenetic diversity metrics of alpha diversity. Microbial community structure was significantly different between baseline and after Ramadan samples according to unweighted UniFrac analysis (P=0.025). LEfSe analysis revealed that Butyricicoccus, Bacteroides, Faecalibacterium, Roseburia, Allobaculum, Eubacterium, Dialister and Erysipelotrichi were significantly enriched genera after the end of Ramadan fasting. According to random forest analysis, the bacterial species most affected by the Ramadan fasting was Butyricicoccus pullicaecorum. Despite this is a pilot study with a limited sample size; our results clearly revealed that Ramadan fasting, which represents an intermittent fasting regime, leads to compositional changes in the gut microbiota.
... Few studies have been conducted regarding the connection between RIF and gut microbiota. In their study, Özkul et al. reported that while Bacteroidetes and A. muciniphila increased during RIF, the abundance of the Firmicutes Butyricicoccus, Faecalibacterium, and Roseburia also increased (Ozkul et al., 2020). Ikram et al. found that Dorea, Klebsiella, and Faecalibacterium were more common in the Muslim Chinese group after RIF, and Sutterella, Parabacteroides, and Alistipes were significantly enriched in the Pakistani group. ...
... The results showed that at the phylum level, Firmicutes decreased only in the Pakistani group. However, Özkul et al. found no significant changes in Firmicutes levels after Ramadan (Ozkul et al., 2020). According to Mohammadzadeh et al., there was a significant increase in Firmicutes (13%) after Ramadan (p < 0.05) (Mohammadzadeh et al., 2021). ...
... According to Mohammadzadeh et al., there was a significant increase in Firmicutes (13%) after Ramadan (p < 0.05) (Mohammadzadeh et al., 2021). Our study did not show any change in the Bacteriodetes levels, contrary to the results of these previous reports (Ozkul et al., 2020;Mohammadzadeh et al., 2021). Bacteroidetes and Proteobacteria, known to utilize host-derived energy substrates, simultaneously increased. ...
Much research has been conducted regarding the impact of diet on the gut microbiota. However, the effects of dietary habits such as intermittent fasting are unclear. This study aimed to investigate the effect of intermittent fasting during Ramadan on the gut microbiota. The study was conducted on 12 healthy adult individuals who practiced fasting 17 h per day for 29 consecutive days during the month of Ramadan. To determine the dietary intake of individuals, a 3-day dietary record was kept at the beginning and end of the study. Reads that passed quality filtering were clustered, and custom-prepared 16S rRNA gene regions of bacteria associated with the human microbiome were used as a reference. Consensus sequences were created, and genus-level taxonomic annotations were determined using a sequence identity threshold of 95%. The correlations between the dietary intake measurements of the participants and the respective relative abundance of bacterial genera were investigated. The results showed that Firmicutes were higher in abundance in the gut microbiota before fasting among participants, while they were significantly lower in abundance at the end of Ramadan fasting ( p < 0.05). Proteobacteria were significantly higher in abundance at the end of the month of Ramadan ( p < 0.05). Fasting was associated with a significant decrease in levels of seven genera: Blautia, Coprococcus, Dorea, Faecalicatena, Fusicatenibacter, Lachnoclostridium , and Mediterraneibacter . Conversely, the abundances of two bacterial genera were enhanced at the end of the fasting month: Escherichia and Shigella . The results of the dietary intake analysis showed that a negative correlation was detected for three comparisons: Ihubacter and protein (rho = −0.54, p = 0.0068), Fusicatenibacter and vegetables (rho = −0.54, p = 0.0042), and Intestinibacter and nuts (rho = −0.54, p -value = 0.0065). The results suggest that even when the fasting period during Ramadan is consistent, the types of food consumed by individuals can affect the gut microbiota.
... Another study by Suleiman et al. discovered that intermittent fasting enhanced insulin sensitivity and decreased blood pressure in type 2 diabetic patients [10]. However, despite their divergent objectives and approaches, a number of previous studies have overlooked the distinction between Ramadan and intermittent fasting and regarded them as equivalent [11][12][13][14][15][16]. Muslims undergo significant lifestyle changes during Ramadan, such as altered sleep patterns, water scarcity, and mealtimes. ...
... In recent decades, Ramadan fasting has been equated with intermittent fasting, and thus, has been promoted for its potential health benefits [43][44][45]. Preliminary studies investigating the potential relationship between Ramadan fasting and the gut microbiome have employed either a cross-sectional design comparing a fasting group (those participating in Ramadan fasting) with a group refeeding after Ramadan [11][12][13], or have used a longitudinal design monitoring changes in the gut microbiota over the course of the Ramadan month [14][15][16]. To the best of our knowledge, this is the first study to track changes in the gut microbiome throughout and then after Ramadan. ...
... Interestingly, these results are consistent with changes in SCFAs, including acetic acid, butyric acid, and propionic acid. Although the limited sample size for the SCFA assessment did not allow for the calculation of statistical p-values among the groups, the apparent decrease in the three SCFAs during the Ramadan fasting period and their return to normal levels after refeeding confirm our findings and also contradict previous studies [11][12][13][14][15][16]. Furthermore, the association between the three assessed SCFAs and microorganisms has helped us understand the health-related roles of microbial communities. ...
An intermittent fasting regimen is widely perceived to lead to various beneficial health effects, including weight loss, the alleviation of insulin resistance, and the restructuring of a healthy gut microbiome. Because it shares certain commonalities with this dietary intervention, Ramadan fasting is sometimes misinterpreted as intermittent fasting, even though there are clear distinctions between these two regimens. The main purpose of this study is to verify whether Ramadan fasting drives the same beneficial effects as intermittent fasting by monitoring alterations in the gut microbiota. We conducted a study involving 20 Muslim individuals who were practicing Ramadan rituals and assessed the composition of their gut microbiomes during the 4-week period of Ramadan and the subsequent 8-week period post-Ramadan. Fecal microbiome analysis was conducted, and short-chain fatty acids (SCFAs) were assessed using liquid-chromatography–mass spectrometry. The observed decrease in the levels of SCFAs and beneficial bacteria during Ramadan, along with the increased microbial diversity post-Ramadan, suggests that the daily diet during Ramadan may not provide adequate nutrients to maintain robust gut microbiota. Additionally, the notable disparities in the functional genes detected through the metagenomic analysis and the strong correlation between Lactobacillus and SCFAs provide further support for our hypothesis.
... Considering that both dietary regimens may be significant modulators of health and microbiota diversity, the aim of this systematic review is to summarize the effects of the TRE and RF regimens on the composition of the gut microbiota in both animal and human studies. Extensive research using both animal models 10,11,14,15,16 and humans 17,18 demonstrates that both TRE and RF yield beneficial changes in the metabolic parameters associated with obesity; for this reason, the aim was also to investigate whether the changes in these host metabolic parameters are associated with changes in the composition of the gut microbiota. ...
... 22 The 3 RF human studies all had an observational design. 17,18,29 Six studies enrolled apparently healthy individuals, 17,18,21,22,23,29 while 1 study enlisted patients with obesity. 25 All participants were aged from 18 to 56 years (Table 3 17,18,21,22,23,25,29 ). ...
... 22 The 3 RF human studies all had an observational design. 17,18,29 Six studies enrolled apparently healthy individuals, 17,18,21,22,23,29 while 1 study enlisted patients with obesity. 25 All participants were aged from 18 to 56 years (Table 3 17,18,21,22,23,25,29 ). ...
Context:
It is well known that the microbiome undergoes cyclical diurnal rhythms. It has thus been hypothesized that meal timing may affect gut microbial composition, function, and host health.
Objective:
This review aims to examine the effects of time-restricted eating (TRE) and Ramadan fasting (RF) on the composition of the gut microbiota in animal and human studies. The associations between composition of microbiota and host metabolic parameters are also examined.
Data sources:
A search was performed on the PubMed, Cochrane, Scopus, and Web of Science databases up to December 31, 2022. The search strategy was performed using the Medical Subject Heading (MeSH) terms "intermittent fasting" and "gastrointestinal microbiome" and the key words "Ramadan fasting" and "microbes."
Data extraction:
Seven human studies (4 TRE and 3 RF) and 9 animal studies (7 TRE, 2 RF-like) were retrieved.
Data analysis:
TRE and RF in human studies lead to an increase in gut microbial community alpha-diversity. In animal studies (both TRE and RF-like), fasting is not associated with improved alpha-diversity, but enhancement of microbial fluctuation is observed, compared with high-fat diet ad libitum groups. Within Firmicutes and Bacteroidetes phyla, no specific direction of changes resulting from fasting are observed in both animals and human. After TRE or RF, a greater abundance of the Faecalibacterium genus is observed in human studies; changes in Lactobacillus abundance are found in animal studies; and increases in Akkermansia are seen both in humans and in animals fed a feed-pellet diet. Only 2 human studies show a beneficial correlation between microbiota changes and host metabolic (HDL cholesterol) or anthropometric parameters (body mass index).
Conclusions:
These findings support the importance of both regimens in improving the gut microbiota composition. However, based on results of animal studies, it can be suggested that diet remains the essential factor in forming the microbiota's environment.
Systematic review registration:
PROSPERO registration no. CRD42021278918.
... Depending on the evaluation method, the effects of Ramadan fasting on the microbiota diversity of healthy, normal-weight participants are contradictory. Operational taxonomical units (OTUs) data revealed a significant increase in microbial diversity during Ramadan [43]. Ozkul et al. [43] and Mindikoglu et al. [44] found no differences in αdiversity measurements following the Ramadan fast, whereas another study found a significant increase in α-diversity following the fast in a young cohort [45]. ...
... Operational taxonomical units (OTUs) data revealed a significant increase in microbial diversity during Ramadan [43]. Ozkul et al. [43] and Mindikoglu et al. [44] found no differences in αdiversity measurements following the Ramadan fast, whereas another study found a significant increase in α-diversity following the fast in a young cohort [45]. In the group of middleaged individuals, however, this effect was not statistically significant [45]. ...
... In the group of middleaged individuals, however, this effect was not statistically significant [45]. The β-diversity analysis of revealed a significant difference between the pre-and post-Ramadan microbial community structure in Ozkul's [43] and Su's [45] studies, but not in Mindikoglu's [44]. Following the cessation of fasting, the gut microbial community exhibited a strong tendency to return to baseline levels [45]. ...
Intermittent fasting (IF) has been promoted as an alternative to dietary caloric restriction for the treatment of obesity. IF restricts the amount of food consumed and improves the metabolic balance by synchronizing it with the circadian rhythm. Dietary changes have a rapid effect on the gut microbiota, modulating the interaction between meal timing and host circadian rhythms. Our paper aims to review the relationships between IF and human gut microbiota. In this study, the primary area of focus was the effect of IF on the diversity and composition of gut microbiota and its relationship with weight loss and metabolomic alterations, which are particularly significant for metabolic syndrome characteristics. We discussed each of these findings according to the type of IF involved, i.e., time-restricted feeding, Ramadan fasting, alternate-day fasting, and the 5:2 diet. Favorable metabolic effects regarding the reciprocity between IF and gut microbiota changes have also been highlighted. In conclusion, IF may enhance metabolic health by modifying the gut microbiota. However additional research is required to draw definitive conclusions about this outcome because of the limited number and diverse designs of existing studies.
... Some studies have linked the composition of the gut microbiome to religion [89][90][91][92][93][94]. However, this connection is based on the diets followed by people of one religion or another [95]. ...
... For one month, Muslims eat between sunset and sunrise 104]. As a result, the fasting microbiome is characterized by several features [90][91][92][93]. At the end of Ramadan, the gut community was shown to be enriched with the following bacterial taxa: Butyricicoccus, Bacteroides, Faecalibacterium, Roseburia, Allobaculum, Eubacterium, Dialister, and Erysipelotrichia. ...
... At the end of Ramadan, the gut community was shown to be enriched with the following bacterial taxa: Butyricicoccus, Bacteroides, Faecalibacterium, Roseburia, Allobaculum, Eubacterium, Dialister, and Erysipelotrichia. At the same time, the content of Butyricicoccus pullicaecorum was reduced relative to its concentration before the start of fasting [91][92][93]. The results of these studies are based on the fact that this type of fasting leads to an increase in the gut contents of Akkermansia muciniphila [91,92] and Bacteroides fragilis [91]. ...
High-throughput sequencing has made it possible to extensively study the human gut microbiota. The links between the human gut microbiome and ethnicity, religion, and race remain rather poorly understood. In this review, data on the relationship between gut microbiota composition and the nationality of people and their religion were generalized. The unique gut microbiome of a healthy European (including Slavic nationality) is characterized by the dominance of the phyla Firmicutes, Bacteroidota, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia. Among the African population, the typical members of the microbiota are Bacteroides and Prevotella. The gut microbiome of Asians is very diverse and rich in members of the genera Prevotella, Bacteroides Lactobacillus, Faecalibacterium, Ruminococcus, Subdoligranulum, Coprococcus, Collinsella, Megasphaera, Bifidobacterium, and Phascolarctobacterium. Among Buddhists and Muslims, the Prevotella enterotype is characteristic of the gut microbiome, while other representatives of religions, including Christians, have the Bacteroides enterotype. Most likely, the gut microbiota of people of different nationalities and religions are influenced by food preferences. The review also considers the influences of pathologies such as obesity, Crohn’s disease, cancer, diabetes, etc., on the bacterial composition of the guts of people of different nationalities.
... The gut microbiome, which is the host microbial community with distinct metabolic properties, shows circadian variations in its composition, and animal studies have shown that TRF contributes to these daily cyclic fluctuations [11]. Few human studies on small numbers of subjects are at present available on this topic, showing that TRE increased abundance of Akkermansia muciniphila and the Bacteroides fragilis group [12] and enhanced gut-microbial richness, with enrichment of Prevotellaceae and Bacteroideaceae [6,13,14], particularly increasing the abundance of Butyricicoccus pullicaecorum [15]. On the other hand, other authors failed to find differences between time-restricted and unrestricted regimens [16], and animal experiments in pediatric mice even found disturbed microbiota-host relationships and persistent gut-flora impairments after TRF [17,18]. ...
... A few human studies are available with contrasting results [6,[12][13][14][15][16]. We failed to find between-group differences in gut-microbial alpha diversity, contrarily to authors showing enhanced values with TRE [6] but in line with others [15,16]. ...
... A few human studies are available with contrasting results [6,[12][13][14][15][16]. We failed to find between-group differences in gut-microbial alpha diversity, contrarily to authors showing enhanced values with TRE [6] but in line with others [15,16]. We cannot rule out that our fasting interval could have played a role, since an early TRE (with the last meal of the day at 3:00 p.m.) determined a significant increase in alpha diversity, while a later TRE (with the last meal at 8:00 p.m.) failed to demonstrate any differences in bacterial richness versus the control group's unrestricted eating [14]. ...
The metabolic benefits of time-restricted eating (TRE) in humans are statistically significant but not clinically relevant. Few data are available about the effects of TRE on the gut microbiota. We compared the effects of a TRE regimen (<12 h feeding; n = 25) with a time-unrestricted (TUE) regimen (>12 h feeding; n = 24), on the clinical and dietary variables and gut-microbiota composition in patients with obesity, who were subjected for 12 weeks to the same caloric restriction. Median weight loss was 4.0 kg and 2.2 kg in the TRE and TUE groups, respectively, with a between-group borderline difference (p = 0.049). No significant between-group difference was found in other dietary, anthropometric, or laboratory variables. There were no substantial between-group differences in alpha and beta diversity or gut-microbiota composition. The TRE group showed a significant increase in the frequency of Lachnospiraceae, Parasutterella, and Romboutsia at the study's end. A TRE regimen induced small changes both in metabolic/dietary variables and in the gut-microbiota composition, with respect to the TUE. The microbial changes we have found were of uncertain clinical significance.
... Of the corresponding authors of the selected studies, 9 were in China, 27,35,36,38,40,41,44,45,48 6 were in the United States, 12,34,37,39,42,43 and 2 were in Turkey. 46,47 ...
... 12,27,[34][35][36][37][38][39][40][41][42] On the other hand, in studies with a human model, a medium to high risk of bias was identified, due mainly to the nature of the interventions in relation to: (1) impossibility of blinding the participants and evaluators; (2) potentially incomplete recalls 43-48 ; (3) loss of samples/participants; (4) absence of groups without intervention; and (5) heterogeneous and/or small groups. 43,46,47 Interventions, population, comparators, and effects on intestinal microbiota ...
... These MADF cycles reduced intestinal inflammation, increased stem cell number, stimulated protective gut microbiota, and reversed intestinal pathology caused by DSS, whereas water-only fasting increased regenerative and reduced inflammatory markers without reversing pathology. 34 Gabel et al. (2020) 43 evaluated the effects of TRF (16:8) in obese adult individuals for 12 weeks (Table 4) [43][44][45][46][47][48] (without making any other restrictions on the type, quality, or quantity of the food) on body composition, biochemical parameters and IM compared with individuals without restriction on feeding time. Body weight decreased. ...
Context
Several therapies have been tested for combating weight gain and obesity-related metabolic diseases, and among these therapies, intermittent fasting (IF) has gained a great deal of interest.
Objective
The aim of this study was to provide the reader with a current survey of IF protocols and an understanding of the outcomes found to date in terms of the profile of the intestinal microbiota (IM) in obese organisms.
Data Sources
Data were obtained from 4 databases: PubMed, SCOPUS, LILACs, and Web of Science.
Data Extraction
Data from studies relating IF protocols to the microbiota and weight loss were extracted using a protocol in START program.
Data Analysis
Of the 82 original articles identified from the databases, 35 were eliminated due to duplication, and 32 were excluded due to not meeting the inclusion criteria. Two additional articles found in a new search were added, yielding a total of 17 studies to be included in this review. Among the protocols, alternate-day fasting (ADF) and time-restricted feeding (TRF) were the most common, and they were shown to have different mechanisms of metabolic signaling. TRF influences weight control and biochemical parameters by regulating the circadian system, and improving satiety control systems by acting on leptin secretion. On the other hand, ADF leads to a reduction of ±75% of all energy consumption regardless of dietary composition in addition to promoting hormonal adjustments that promote weight control. Furthermore, both protocols showed the ability to remodel the IM by changing the Firmicutes/Bacteroidetes ratio and increasing the abundance of strains such as Lactobacillus spp. and Akkermansia m. that have a protective effect on metabolism against the effects of weight gain.
Conclusion
In short, the ADF and TRF protocols have a positive effect on the remodeling of the IM and can possibly be used to control body adiposity, improve insulin sensitivity, and achieve other obesity-related metabolic changes.
... Accordingly, DR could modulate human gut microbiota, and the gut microbiota also has been proposed to affect some health benefits of DR. The most frequently found gut microbiota impact of DR in humans is the enrichment of Akkermansia (Dong et al. 2020;Ozkul, Yalinay, and Karakan 2020;von Schwartzenberg et al. 2021), Bifidobacterium (Dong et al. 2020;Mesnage et al. 2019;Ott et al. 2017), Faecalibacterium (Cignarella et al. 2018;Maifeld et al. 2021;Ozkul, Yalinay, and Karakan 2020;Ruiz et al. 2017;Zeb et al. 2020), and Parabacteroides (Ali et al. 2021;Benítez-Páez et al. 2021;Gutiérrez-Repiso et al. 2021;Stanislawski et al. 2021). Akkermansia and Bifidobacterium, the promising probiotics, have physiological advantages in several clinical settings. ...
... Accordingly, DR could modulate human gut microbiota, and the gut microbiota also has been proposed to affect some health benefits of DR. The most frequently found gut microbiota impact of DR in humans is the enrichment of Akkermansia (Dong et al. 2020;Ozkul, Yalinay, and Karakan 2020;von Schwartzenberg et al. 2021), Bifidobacterium (Dong et al. 2020;Mesnage et al. 2019;Ott et al. 2017), Faecalibacterium (Cignarella et al. 2018;Maifeld et al. 2021;Ozkul, Yalinay, and Karakan 2020;Ruiz et al. 2017;Zeb et al. 2020), and Parabacteroides (Ali et al. 2021;Benítez-Páez et al. 2021;Gutiérrez-Repiso et al. 2021;Stanislawski et al. 2021). Akkermansia and Bifidobacterium, the promising probiotics, have physiological advantages in several clinical settings. ...
In recent times, dietary restriction (DR) has received considerable attention for its promising effects on metabolism and longevity. Previous studies on DR have mainly focused on the health benefits produced by different restriction patterns, whereas comprehensive reviews of the role of gut microbiota during DR are limited. In this review, we discuss the effects of caloric restriction, fasting, protein restriction, and amino acid restriction from a microbiome perspective. Furthermore, the underlying mechanisms by which DR affects metabolic health by regulating intestinal homeostasis are summarized. Specifically, we reviewed the impacts of different DRs on specific gut microbiota. Additionally, we put forward the limitations of the current research and suggest the development of personalized microbes-directed DR for different populations and corresponding next-generation sequencing technologies for accurate microbiological analysis. DR effectively modulates the composition of the gut microbiota and microbial metabolites. In particular, DR markedly affects the rhythmic oscillation of microbes which may be related to the circadian clock system. Moreover, increasing evidence supports that DR profoundly improves metabolic syndrome, inflammatory bowel disease, and cognitive impairment. To summarize, DR may be an effective and executable dietary manipulation strategy for maintaining metabolic health, however, further investigation is needed to elucidate the underlying mechanisms.
... The study explored nocturnal fasting, and the findings may not be relevant to diurnal fasting, such as Ramadan fasting, due to impacts of the circadian rhythm and differences in mealtimes. Although the salivary microbiome has not been studied specifically during fasting, the impact of fasting (during Ramadan) has been investigated on the gut microbiome [111][112][113]. In these studies, the gut microbiome was reported to alter during Ramadan fasting [111][112][113]. ...
... Although the salivary microbiome has not been studied specifically during fasting, the impact of fasting (during Ramadan) has been investigated on the gut microbiome [111][112][113]. In these studies, the gut microbiome was reported to alter during Ramadan fasting [111][112][113]. It was suggested that upregulation of butyric acid-producing Lachnospiraceae may provide a mechanistic explanation for the health benefits of intermittent fasting [113]. ...
... The metagenome sequencing of V3-4 variable regions of the bacterial 16S ribosomal RNA was carried out by the NovoGene Company (Beijing, China). Data processing and analysis were performed according to routine procedures, which have been described elsewhere in detail (8)(9)(10)(11). ...
... In addition, the alterations observed within the bacterial communities might also be provoked by metabolic or immune modifications within host cells such as the production of hormones or ketone bodies, as these factors are known to shape the gut microbiota composition and its function (13,14). Among the effects, the upregulation of Lachnospiraceae and Ruminococcaceae during the fasting was the most notable and this aligns well with the studies of others associating these bacteria as important drivers for health effects of IF (8,9). Over last decade, gut microbiota has attracted great scientific and public attention, and is widely recognized as the nexus of the interaction between life style (e.g., dietary habits) and health status (10). ...
Recently we reported that in healthy volunteer Ramadan-associated intermittent fasting (RAIF) remodels the gut microbiome and resulted in an increase in small chain fatty acid producing bacteria concomitant with improved metabolic parameters. As interpretation of these results is hampered by the possible psychological effects associated with the study, we now aim to investigate RAIF in experimental animals. To this end, 6-week male BALB/c mice were subjected to RAIF (30 days of a 16-h daily fasting; n = 8) or provided with feed ad libitum ( n = 6). Fecal samples were collected before and the end of fasting and bacterial 16S rRNA sequencing was performed. We found that RAIF remodeled the composition of gut microbiota in BALB/c mice ( p < 0.01) and especially provoked upregulation of butyrate acid-producing Lachnospireceae and Ruminococcaceae ( p < 0.01), resembling the effects seen in human volunteers. Hence we conclude that the effects of RAIF on gut microbiome relate to the timing of food intake and are not likely related to psychological factors possibly at play during Ramadan.
... Moreover, studies showed that HFD-induced obese mice exhibited reduced body weight and improved lipid metabolism linked with a higher proportion of A. muciniphila and Lactobacillus following 4 days of complete food withdrawal [312]. In non-obese adults, both TRF and ADF lead to an increase in the abundance of Bacteroides [307,313,314]. In healthy adults that underwent 29 days of TRF (Ramadan fasting regimen), an increase in Bacteroides fragilis, A. muciniphila, Butyricicoccus, Faecalibacterium, Roseburia, Allobaculum, Eubacterium, Dialister, and Erysipelotrichi was observed [313,314]. ...
... In non-obese adults, both TRF and ADF lead to an increase in the abundance of Bacteroides [307,313,314]. In healthy adults that underwent 29 days of TRF (Ramadan fasting regimen), an increase in Bacteroides fragilis, A. muciniphila, Butyricicoccus, Faecalibacterium, Roseburia, Allobaculum, Eubacterium, Dialister, and Erysipelotrichi was observed [313,314]. In overweight or obese adults, an increase in Lactobacillus, A. muciniphila, Faecalibacterium prausnizii, and Enterobacteria abundances was reported after a TRF intervention [315]. ...
Background
Despite decades of research, managing body weight remains an unsolved clinical problem. Health problems associated with dysregulated body weight, such as obesity and cachexia, also exhibit gut microbiota alterations. There is increased interest in utilising the gut microbiota for body weight control, as it responds to intervention and plays an important role in energy extraction from food as well as biotransformation of nutrients.
Scope of Review
This review provides an overview of the role of the gut microbiota in the physiological and metabolic alterations observed in two body weight dysregulation-related disorders, obesity and cachexia. Secondly, we synthesis the available evidence for different strategies’ – including caloric restriction, intermittent fasting, ketogenic diet, bariatric surgery, probiotics, prebiotics, synbiotics, high-fibre diet and fermented foods – effects on body weight and gut microbiota composition. This approach was used to give insights on the possible link between body weight control and gut microbiota configuration.
Major Conclusions
Despite extensive associations between body weight and gut microbiota composition, there has been limited success in the translation of microbiota-related interventions for body weight control in humans. Manipulation of the gut microbiota alone is insufficient to alter body weight and future research is needed combining strategies to enhance the effects of lifestyle interventions.
... Studies of dawn to sunset fasting showed findings suggestive of beneficial alterations in the gut microbiome (109,110). A study conducted on both healthy young and middle-aged cohorts showed a significantly increased gut microbiome diversity and remodeling of the gut microbiome in the young cohort during and at the end of dawn to sunset fasting month compared to baseline levels. ...
... While this study found a significant increase in Bacteroidetes and a decrease in Firmicutes in the Pakistani group, a similar effect was not observed in the Chinese group, likely related to the dietary effect on the microbiome (111). A smaller study showed a significant beta diversity and enrichment in the Bacteroidetes phylum after 29 days of dawn to sunset fasting (110). The enrichment in Bacteroidetes phylum after dawn to sunset fasting is important because the reduction in Bacteroidetes/Firmicutes ratio was shown to play an important role in the development of obesity (112,113). ...
Dawn to sunset fasting, a type of intermittent fasting commonly practiced in the month of Ramadan, requires fasting from dawn to sunset without food or liquid intake. Dawn and dusk are two transition time zones of the day that play a critical role in the human circadian rhythm. Practicing dawn to sunset fasting requires the alignment of mealtimes and wake-sleep times with the human biological dawn and dusk.
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) impairs immune cell responses at multiple levels and leads to severe Coronavirus Disease 2019 (COVID-19). It generates high levels of pro-inflammatory cytokines and chemokines, also known as a cytokine storm, leads to mitochondrial dysfunction and generation of excessive amounts of mitochondrial reactive oxygen species, downregulates autophagy to escape detection for unchecked replication, and alters gut microbiome composition. Severe cases of COVID-19 have been associated with several comorbidities that impair immune responses (e.g., obesity, diabetes, malignancy) and blood laboratory abnormalities (e.g., elevated procalcitonin, C-reactive protein, interleukin-6 (IL-6), leukocytosis, lymphopenia).
Several studies of dawn to sunset fasting showed anti-inflammatory effect by suppressing several pro-inflammatory cytokines, reducing oxidative stress, inducing a proteome response associated with increased autophagy, remodeling the gut microbiome, and improving the components of metabolic syndrome (e.g., obesity, blood glucose levels, blood pressure, lipids).
In conclusion, dawn to sunset fasting has the potential to optimize the immune system function against SARS‐CoV‐2 during the COVID-19 pandemic as it suppresses chronic inflammation and oxidative stress, improves metabolic profile, and remodels the gut microbiome. This review presents scientific literature related to the effects of dawn to sunset fasting on the immune system. Studies are needed to assess and confirm the potential benefits of dawn to sunset fasting against SARS-CoV-2.
... Intermittent fasting also promote the microbial fermentation which in turn lead to formation of some bio products that have beneficial effects on metabolic disorders such as obesity, insulin resistance and hepatic steatosis [13]. Recent evidences have been published in favor of the gut microbial shifts and functional consequences for the host in intermittent fasting regimes [14][15][16]. However, there is no previous systematic review summarizing and comparing the alterations of the intestinal bacterial composition and functions following the different kind of fasting. ...
... After Ramadan fasting, an increase in microbial richness was observed and the frequency of Butyricicoccus, Bacteroides, Faecalibacterium, Roseburia, Allobaculum, Eubacterium, Dialister, and Erysipelotrichi increased. The bacterial species most affected by the Ramadan fasting was Butyricicoccus pullicaecorum, Akkermansia muciniphila and Bacteroides fragilis which led to reduction of serum fasting glucose and total cholesterol levels [15,46]. Su J, et al. evaluated the effect of Ramadan fasting (16 h of fasting/day during a 30-day period) on the gut microbiota. ...
Background
Intermittent fasting has been reported to have positive effects on obesity, diabetes, cardiovascular diseases, hypertension, and several neurodegenerative diseases through different mechanisms such as alteration in the gut microbiota. This systematic review was conducted with the aim of providing an overview of the existing animal and human literature regarding the gut microbiota alterations in various fasting regimens.
Method
A systematic literature search was conducted on PubMed, Scopus and Web of Science databases up to May 2021 to find all relevant studies examining the gut microbiota alteration during the fasting. Original researches on animal models or human patients were included in this study.
Results
The search fulfilled 3072 documents from which 31 studies (20 animal and 11 human studies) were included. Upon fasting, abundance of several beneficial bacteria including Lactobacillus and Bifidobacterium shifted significantly. Moreover, some taxa, including Odoribacter which negatively associated with blood pressure bloomed during fasting. Ramadan fasting, as a kind of intermittent fasting, improves health parameters through positive changes in gut microbiota including upregulation of A. muciniphila, B. fragilis, Bacteroides and butyric acid–producing Lachnospiraceae .
Conclusion
The findings suggest that different fasting regimens including alternate-day fasting, calorie- and time-restricted fasting programs and Ramadan fasting could promote health maybe through the modulation of gut microbiome. However, further studies are needed to explore properly the connection between gut microbiota and meal frequency and timing.
... For this reason, it is important to investigate the effects of these drugs other than those known in diabetic models in terms of safe drug use in diabetic patients [31,32]. Despite remarkable scientific interest in the well-defined effects of various antibiotics [19,33,34] and non-antibiotic drugs [35] across microbial community structure, the impact of antipsychiatry drugs on the gut microbiome has generally been disregarded [36]. In this context, with this study, we investigated the effect of RXB, an antidepressant, on gut flora. ...
... Drug administrations, including antidepressants, have differential effects on the Firmicutes/Bacteroidetes ratio. In our study, the Firmicutes/Bacteroidetes ratio decreased in both healthy and diabetic rats after RBX administration [33,40,42,43]. Interestingly, research by Cusotto et al. (2019) showed that, by investigating the effects of various psychotropics on gut microbiota, the Bacteroidetes levels significantly decreased after administering the antipsychotic drugs lithium, valproate, and aripiprazole [36]. ...
Antidepressants are drugs commonly used in clinical settings. However, there are very limited studies on the effects of these drugs on the gut microbiota. Herein, we evaluated the effect of reboxetine (RBX), a selective norepinephrine (noradrenaline) reuptake inhibitor (NRI), on gut microbiota in both diabetic and non-diabetic rats. This is the first report of relation between reboxetine use and the gut microbiota to our knowledge. In this study, type-1 diabetes induced by using streptozotocin (STZ) and RBX was administered to diabetic rats and healthy controls for 14 days. At the end of the treatment, stool samples were collected. Following DNA extraction, amplicon libraries for the V3-V4 region were prepared and sequenced with the Illumina Miseq platform. QIIME was used for preprocessing and analysis of the data. As a result, RBX had a significant effect on gut microbiota structure and composition in diabetic and healthy rats. For example, RBX exposure had a pronounced microbial signature in both groups, with a low Firmicutes/Bacteroidetes ratio and low Lactobacillus levels. While another abundance phylum after exposure to RBX was Proteabacteria, other notable taxa in the diabetic group included Flavobacterium, Desulfovibrionaceae, Helicobacteriaceae, Campylobacterales, and Pasteurellacae when compared to the untreated group.
... 87 The rationale that caloric restriction impacts the microbiome is intriguing; nevertheless, robust data in humans are still scarce. 90,[134][135][136][137] Mesnage et al 90 investigated the effect of a 10-day periodic fast on the fecal microbiota of 15 healthy men. Fasting caused a decrease in Lachnospiraceae and Ruminococcaceae. ...
... 90 A small human pilot study showed that Ramadan fasting affected the microbiome of healthy subjects enriching several SCFA producers. 135,138 We evaluated the impact of fasting in metabolic syndrome patients. In a clinical study, 35 metabolic syndrome patients underwent a 5-day fast followed by 3 weeks of DASH diet. ...
The pathogenesis of hypertension is known to involve a diverse range of contributing factors including genetic, environmental, hormonal, hemodynamic and inflammatory forces, to name a few. There is mounting evidence to suggest that the gut microbiome plays an important role in the development and pathogenesis of hypertension. The gastrointestinal tract, which houses the largest compartment of immune cells in the body, represents the intersection of the environment and the host. Accordingly, lifestyle factors shape and are modulated by the microbiome, modifying the risk for hypertensive disease. One well-studied example is the consumption of dietary fibers, which leads to the production of short-chain fatty acids and can contribute to the expansion of anti-inflammatory immune cells, consequently protecting against the progression of hypertension. Dietary interventions such as fasting have also been shown to impact hypertension via the microbiome. Studying the microbiome in hypertensive disease presents a variety of unique challenges to the use of traditional model systems. Integrating microbiome considerations into preclinical research is crucial, and novel strategies to account for reciprocal host-microbiome interactions, such as the wildling mouse model, may provide new opportunities for translation. The intricacies of the role of the microbiome in hypertensive disease is a matter of ongoing research, and there are several technical considerations which should be accounted for moving forward. In this review we provide insights into the host-microbiome interaction and summarize the evidence of its importance in the regulation of blood pressure. Additionally, we provide recommendations for ongoing and future research, such that important insights from the microbiome field at large can be readily integrated in the context of hypertension.
... Traditionally, fasting plays an important role in different cultural and religious practices. Dramatic caloric restriction not only affects host health and physiology, but also has an impact on the microbiome [8][9][10] . Here, we studied the role of fasting in cardiovascular risk patients with MetS (Table 1). ...
... Here we demonstrate that fasting induces changes to the gut microbiome and immune homeostasis with a sustained beneficial effect on body weight and BP in hypertensive MetS patients. There is a growing interest in understanding how dietary interventions shape the gut microbiome and interact with metabolic diseases, including obesity, MetS, type 2 diabetes, and (cardiovascular) health [8][9][10][23][24][25][26][27] . Several lifestyle interventions aimed at weight loss have shown that the gut microbiome changes in obese, type 2 diabetic or MetS patients 10,23,24,26,27 . ...
Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical parameters, the immunome and gut microbiome exploratory endpoints, that in hypertensive metabolic syndrome patients, a 5-day fast followed by a modified Dietary Approach to Stop Hypertension diet reduces systolic blood pressure, need for antihypertensive medications, body-mass index at three months post intervention compared to a modified Dietary Approach to Stop Hypertension diet alone. Fasting alters the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses reveal a positive correlation of circulating mucosa-associated invariant T cells, non-classical monocytes and CD4 ⁺ effector T cells with systolic blood pressure. Furthermore, regulatory T cells positively correlate with body-mass index and weight. Machine learning analysis of baseline immunome or microbiome data predicts sustained systolic blood pressure response within the fasting group, identifying CD8 ⁺ effector T cells, Th17 cells and regulatory T cells or Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia , and Ruminococcaceae as important contributors to the model. Here we report that the high-resolution multi-omics data highlight fasting as a promising non-pharmacological intervention for the treatment of high blood pressure in metabolic syndrome patients.
... Beneficial effects on gut microbiota have been also reported following intermittent fasting, a dietary regimen linked with weight loss and beneficial metabolic effects (i.e., improved glycemic control) [267], increased bacterial alpha diversity, increased Lactobacillus and Bifidobacterium and decreased pathogenic bacteria [268]. During Ramadan (a popular example of intermittent fasting), increased proportion of A. muciniphila, F. prausnitzii and Roseburia have been reported [269,270]. ...
Obesity has reached epidemic proportion worldwide and in all ages. Available evidence points to a multifactorial pathogenesis involving gene predisposition and environmental factors. Gut microbiota plays a critical role as a major interface between external factors, i.e., diet, lifestyle, toxic chemicals, and internal mechanisms regulating energy and metabolic homeostasis, fat production and storage. A shift in microbiota composition is linked with overweight and obesity, with pathogenic mechanisms involving bacterial products and metabolites (mainly endocannabinoid-related mediators, short-chain fatty acids, bile acids, catabolites of tryptophan, lipopolysaccharides) and subsequent alterations in gut barrier, altered metabolic homeostasis, insulin resistance and chronic, low-grade inflammation. Although animal studies point to the links between an “obesogenic” microbiota and the development of different obesity phenotypes, the translational value of these results in humans is still limited by the heterogeneity among studies, the high variation of gut microbiota over time and the lack of robust longitudinal studies adequately considering inter-individual confounders. Nevertheless, available evidence underscores the existence of several genera predisposing to obesity or, conversely, to lean and metabolically health phenotype (e.g., Akkermansia muciniphila, species from genera Faecalibacterium, Alistipes, Roseburia). Further longitudinal studies using metagenomics, transcriptomics, proteomics, and metabolomics with exact characterization of confounders are needed in this field. Results must confirm that distinct genera and specific microbial-derived metabolites represent effective and precision interventions against overweight and obesity in the long-term.
... Relatively few human studies have been conducted to assess IF-induced changes in the gut microbiota and the relationship with weight loss and host metabolism, and even for these few studies, only the 16S rRNA gene amplicon sequencing approach was applied, hampering analyses at the species level 29,30 . These studies reported that ADF and Ramadan would lead to an increase in the relative abundance of Bacteroidaceae and Bacteroides in multiple sclerosis patients and healthy adults, respectively 31,32 , whereas other reported that IFinduced changes in taxonomic composition of gut microbiota were not consistent in published articles. In this study, we observed that the relative abundances of multiple Bacteroides and Parabacteroides species, especially the reported beneficial bacteria P. distasonis and B. thetaiotaomicron, were significantly increased after the IF intervention. ...
Intermittent fasting (IF) is a promising paradigm for weight loss which has been shown to modulate the gut microbiota based on 16S rRNA gene amplicon sequencing. Here, 72 Chinese volunteers with a wide range of body mass index (BMI) participated in a three-week IF program during which an average loss of 3.67 kg body weight accompanied with improved clinical parameters was observed irrespective of initial anthropometric and gut microbiota status. Fecal samples were collected before and after the intervention and subjected to shotgun metagenomic sequencing. De novo assembly yielded 2934 metagenome-assembled genomes (MAGs). Profiling revealed significant enrichment of Parabacteroides distasonis and Bacteroides thetaiotaomicron after the intervention, with inverse correlations between their relative abundances and parameters related to obesity and atherosclerotic cardiovascular diseases (ASCVD). MAGs enriched after the intervention showed high richness and diversity of carbohydrate-active enzymes, with an increased relative abundances of genes related to succinate production and glutamate fermentation.
... Preclinical studies have shown that fasting periods induce a "gut rest" which contributes to i) improved gut barrier function (e.g., increased villi length and expression of tight junction proteins [98,99] and reductions in plasma levels of lipopolysaccharide [LPS] [100]) ii) enhanced gut microbial richness [101], iii) enrichment of beneficial bacteria [98][99][100]102]and iv) alteration in microbial pathways involved in fuel utilisation (e.g., upregulation of ketone body pathway), antioxidant signalling (enhancement of glutathione metabolism pathways) and low-grade inflammation (downregulation of the LPS biosynthesis pathway) [100], and v) changes in gut microbiota-associated metabolites (e.g., increases in faecal shortchain fatty acids) [98]. There are limited studies in humans that have assessed such parameters, but of those few, some confirm some beneficial gut microbiota changes after TRE [103] or IF during Ramadan [104,105], while others have shown no significant alterations [106]. Research suggests that the gut microbiome affects bone health through several mechanisms including the production of metabolites (e.g., short-chain fatty acids) that affect bone metabolism, the bioavailability of nutrients important for bone health (e.g., calcium), the regulation of the immune system and hormonal modulation [107,108]. ...
Intermittent fasting (IF) is a promising strategy for weight loss and improving metabolic health, but its effects on bone health are less clear. This review aims to summarize and critically evaluate the preclinical and clinical evidence on IF regimes (the 5:2 diet, alternate-day fasting [ADF] and time-restricted eating/feeding [TRE/TRF]) and bone health outcomes. Animal studies have utilised IF alongside other dietary practices known to elicit detrimental effects on bone health and/or in models mimicking specific conditions, thus, findings from these studies are difficult to apply to humans. Whilst limited in scope, observational studies suggest a link between some IF practices (e.g., breakfast omission) and compromised bone health, although lack of control for confounding factors make these data difficult to interpret. Interventional studies suggest that TRE regimens practiced up to 6 months do not adversely affect bone outcomes and may even slightly protect against bone loss during modest weight loss (<5% of baseline body weight). Most studies on ADF have shown no adverse effects on bone outcomes, while no studies on the "5-2" diet have reported bone outcomes. Available interventional studies are limited by their short duration, small and diverse population samples, assessment of total body bone mass exclusively (by DXA) and inadequate control of factors that may affect bone outcomes, making the interpretation of existing data challenging. Further research is required to better characterise bone responses to various IF approaches using well-controlled protocols of sufficient duration, adequately powered to assess changes in bone outcomes, and designed to include clinically relevant bone assessments.
... The role of ethnicity is not clear because there are many confounding factors or variables that could reduce or increase its weight, like lifestyle (rural vs. urban housing con- text) [20], religion [25][26][27][28][29][30][31], diseases [32,33], and physical activity (high-intensity exercises vs. endurance, sedentary vs. physical activity) [32]. The most stressful factor is probably diet, as it is well known that diet styles and nutrients directly affect the qualitative and quantitative composition of gut microbiota. ...
Many scientific studies reveal a significant connection between human intestinal microbiota, eating habits, and the development of chronic-degenerative diseases; therefore, alterations in the composition and function of the microbiota may be accompanied by different chronic inflammatory mechanisms. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), in which autoreactive immune cells attack the myelin sheaths of the neurons. The purpose of this paper was to describe the main changes that occur in the gut microbiota of MS patients, with a focus on both microbiota and its implications for health and disease, as well as the variables that influence it. Another point stressed by this paper is the role of microbiota as a triggering factor to modulate the responses of the innate and adaptive immune systems, both in the intestine and in the brain. In addition, a comprehensive overview of the taxa modified by the disease is presented, with some points on microbiota modulation as a therapeutic approach for MS. Finally, the significance of gastro-intestinal pains (indirectly related to dysbiosis) was assessed using a case study (questionnaire for MS patients), as was the willingness of MS patients to modulate gut microbiota with probiotics.
... Interesting insights into fasting have been gained by studying Muslims during the holy month of Ramadan, during which individuals fast from dawn to sunset, including water avoidance. After Ramadan, individuals had increased levels of beneficial gut bacteria such as A. muciniphila, F. prausnitzii and Roseburia [128][129][130][131] . Fasting also increased microbial richness and diversity as well as levels of the beneficial SCFA butyrate. ...
Obesity is caused by a long-term difference between energy intake and expenditure - an imbalance that is seemingly easily restored by increasing exercise and reducing caloric consumption. However, as simple as this solution appears, for many people, losing excess weight is difficult to achieve and even more difficult to maintain. The reason for this difficulty is that energy intake and expenditure, and by extension body weight, are regulated through complex hormonal, neural and metabolic mechanisms that are under the influence of many environmental factors and internal responses. Adding to this complexity, the microorganisms (microbes) that comprise the gut microbiota exert direct effects on the digestion, absorption and metabolism of food. Furthermore, the gut microbiota exerts a miscellany of protective, structural and metabolic effects both on the intestinal milieu and peripheral tissues, thus affecting body weight by modulating metabolism, appetite, bile acid metabolism, and the hormonal and immune systems. In this Review, we outline historical and recent advances in understanding how the gut microbiota is involved in regulating body weight homeostasis. We also discuss the opportunities, limitations and challenges of using gut microbiota-related approaches as a means to achieve and maintain a healthy body weight.
... The specific effect of Ramadan fasting on the gut microbiome has not been extensively studied. A pilot study (N=9) from Turkey revealed that that microbial richness was significantly increased at the end of the Ramadan fasting period; no significant differences were found in terms of phylogenetic diversity metrics [56]. Studies in model organisms, such as mice, support the findings in humans and highlight the important changes that can occur to gut microbiota when fasting is conducted. ...
... However, evidence also demonstrates that IF significantly impacts the GM composition and function (24). Much clinical research has employed time-restricted eating regimens in various populations, revealing significant dissimilarity compared to control but no differences in taxa abundance (25)(26)(27)(28). More recent work utilizing IF has shown shifts in GM community metrics and gut-related metabolites compared to control in patients diagnosed with metabolic syndrome (29,30). ...
Nutritional interventions are a promising therapeutic option for addressing obesity and cardiometabolic dysfunction. One such option, intermittent fasting (IF), has emerged as a viable alternative to daily caloric restriction and may beneficially modulate body weight regulation and alter the gut microbiome (GM) and plasma metabolome. This secondary analysis of a larger, registered trial (ClinicalTrials.gov ID: NCT04327141) examined the effect of a four-week intervention comparing one vs. two-consecutive days of IF in combination with protein pacing (IF-P; 4-5 meals/day, >30% protein/day) on the GM, the plasma metabolome, and associated clinical outcomes in overweight and obese adults. Participants (n = 20) were randomly assigned to either a diet consisting of one fasting day (total of 36 h) and six low-calorie P days per week (IF1-P, n = 10) or two fasting days (60 h total) and five low-calorie P days per week (IF2-P, n = 10). The fecal microbiome, clinical outcomes, and plasma metabolome were analyzed at baseline (week 0) and after four weeks. There were no significant time or interaction effects for alpha diversity; however, baseline alpha diversity was negatively correlated with percent body fat change after the four-week intervention (p = 0.030). In addition, beta-diversity for both IF groups was altered significantly by time (p = 0.001), with no significant differences between groups. The IF1-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and Eubacterium fissicatena group (q ≤ 0.007), while the IF2-P group had a significant increase in abundance of Ruminococcaceae Incertae Sedis and a decrease in Eubacterium ventriosum group (q ≤ 0.005). The plasma metabolite profile of IF2-P participants displayed significant increases in serine, trimethylamine oxide (TMAO), levulinic acid, 3-aminobutyric acid, citrate, isocitrate, and glucuronic acid (q ≤ 0.049) compared to IF1-P. Fecal short-chain fatty acid concentrations did not differ significantly by time or between groups (p ≥ 0.126). Interestingly, gastrointestinal symptoms were significantly reduced for the IF2-P group but not for the IF1-P group. Our results demonstrate that short-term IF modestly influenced the GM community structure and the plasma metabolome, suggesting these protocols could be viable for certain nutritional intervention strategies.
... In the present study, we found that gut microbiota richness of dairy cows increased during LDA events, and circulation amino acid pool deficits in LDA events indicated that dairy cows with LDA are characterized by low dry matter intake. Previous studies have explained that intermittent fasting increased the richness and diversity of gut microbiota, which are associated with the balance of energy demand during low-energy intake status (25,26). Notably, a recent study revealed that the microbiota structure was markedly different between the rumen and FIG 6 Prediction of genes based on KEGG orthologs (KO) associated with plasma levels of leucine and isoleucine, and genes involved in leucine-isoleucine degradation and fatty acid beta-oxidation. ...
Left displaced abomasum (LDA) in postpartum dairy cows contributes to significant economic losses. Dairy cows with LDA undergo excessive lipid mobilization and insulin resistance. Although gut dysbiosis is implicated, little is known about the role of the gut microbiota in the abnormal metabolic processes of LDA. To investigate the functional links among microbiota, metabolites, and disease phenotypes in LDA, we performed 16S rDNA gene amplicon sequencing and liquid chromatography tandem mass spectrometry (LC-MS/MS) of fecal samples from cows with LDA (n = 10) and healthy cows (n = 10). Plasma marker profiling was synchronously analyzed. In the LDA event, gut microbiota composition and fecal metabolome were shifted in circulation with an amino acid pool deficit in dairy cows. Compared with the healthy cows, salicylic acid derived from microbiota catabolism was decreased in the LDA cows, which negatively correlated with Akkermansia, Prevotella, non-esteri-fied fatty acid (NEFA), and b-hydroxybutyric acid (BHBA) levels. Conversely, fecal taurolithocholic acid levels were increased in cows with LDA. Based on integrated analysis with the plasma metabolome, eight genera and eight metabolites were associated with LDA. Of note, the increases in Akkermansia and Oscillospira abundances were negatively correlated with the decreases in 4-pyridoxic acid and cytidine levels, and positively correlated with the increases in NEFA and BHBA levels in amino acid deficit, indicating pyridoxal metabolism-associated gut dysbiosis and lipolysis. Changes in branched-chain amino acids implicated novel host-microbial metabolic pathways involving lipolysis and insulin resistance in cows with LDA. Overall, these results suggest an interplay between host and gut microbes contributing to LDA pathogenesis. IMPORTANCE LDA is a major contributor to economic losses in the dairy industry worldwide; however, the mechanisms associated with the metabolic changes in LDA remain unclear. Most previous studies have focused on the rumen microbiota in terms of understanding the contributors to the productivity and health of dairy cows; this study further sheds light on the relevance of the lower gut microbiota and its associated metabolites in mediating the development of LDA. This study is the first to characterize the correlation between gut microbes and metabolic phenotypes in dairy cows with LDA by leveraging multi-omics data, highlighting that the gut microbe may be involved in the regulation of lipolysis and insulin resistance by modulating the amino acid composition.
... The findings in humans are supported by studies in model organisms such as mice, which demonstrate the significant changes in gut microbiota that may occur when fasting is practiced. In healthy mice, intermittent fasting has recently been discovered to reshape the intestinal microbiota, with the duration of the regular fasting period being a key influencing factor [44], [45]. ...
Fasting is one of the five pillars of Islam. Fasting entails more than abstaining from food and drink, fasting improves impulse control and aids in the development of good behavior. The holy month of Ramadan falls on the 9th month of the lunar calendar. Ramadan is a month-long fasting period that takes place between dawn and sunset. Some people with diabetes and those who are sick or have certain medical conditions may be exempt. The majority of people with diabetes, on the other hand, choose to fast; even against medical advice. Many studies have been conducted to determine the health benefits of fasting. Apart from the benefits to the body’s organs, Ramadan fasting is also beneficial for the growth of the gut microbiota and gene expression and is believed to impact the body’s autophagy process. Furthermore, Ramadan fasting has an impact on mental health; TC and LDL were lower, while HDL and TG were higher, lowers inflammation, and oxidative stress markers.
... Another study showed that Ramadan fasting resulted in significant beta diversity and enrichment in the Bacteroidetes phylum (Ozkul et al. 2020). The increase in the Bacteroidetes phylum after Ramadan fasting is important since a decrease in the Bacteroidetes/Firmicutes ratio has been found to play a key role in the development of obesity (Turnbaugh et al. 2006). ...
Religious fasting is practiced by people of all faiths, including Christianity, Islam, Buddhism, Jainism, as well as Hinduism, Judaism, and Taoism. Individual/clinical, public, global, and planetary health has traditionally been studied as separate entities. Nevertheless, religious fasting, in conjunction with other religious health assets, can provide several opportunities, ranging from the individual to the population, environmental, and planetary levels, by facilitating and supporting societal transformations and changes, such as the adoption of healthier, more equitable, and sustainable lifestyles, therein preserving the Earth's systems and addressing major interconnected, cascading, and compound challenges. In this review, we will summarize the most recent evidence on the effects of religious fasting, particularly Orthodox and Ramadan Islamic fasting, on human and public health. Further, we will explore the potential effects of religious fasting on tackling current environmental issues, with a special focus on nutrition/food restriction and planetary health. Finally, specific recommendations, particularly around dietary intake during the fasting rituals, will be provided to ensure a sustainable healthy planet.
... In the past few years, next-generation sequencing technologies have revealed the contribution of the intestinal flora to a variety of pathways related to CV function in health and disease states, including hypertension [139]. For instance, evidence indicates that both fasting and high-fiber food promote a switch in the microbiota composition towards short-chain fatty acid (SCFA)-producing species [140,141]. SCFA, including the most abundant acetate, butyrate, and propionate, are fermentation products of indigestible fibers and promote the differentiation of immune cells towards an antiinflammatory phenotype [142] while also exerting some antioxidant activity [143]. They have also been involved in the epigenetic regulation of several cell types. ...
Hypertension is a major cardiovascular risk factor that is responsible for a heavy burden of morbidity and mortality worldwide. A critical aspect of cardiovascular risk estimation in hypertensive patients depends on the assessment of hypertension-mediated organ damage (HMOD), namely the generalized structural and functional changes in major organs induced by persistently elevated blood pressure values. The vasculature of the eye shares several common structural, functional, and embryological features with that of the heart, brain, and kidney. Since retinal microcirculation offers the unique advantage of being directly accessible to non-invasive and relatively simple investigation tools, there has been considerable interest in the development and modernization of techniques that allow the assessment of the retinal vessels’ structural and functional features in health and disease. With the advent of artificial intelligence and the application of sophisticated physics technologies to human sciences, consistent steps forward have been made in the study of the ocular fundus as a privileged site for diagnostic and prognostic assessment of diverse disease conditions. In this narrative review, we will recapitulate the main ocular imaging techniques that are currently relevant from a clinical and/or research standpoint, with reference to their pathophysiological basis and their possible diagnostic and prognostic relevance. A possible non pharmacological approach to prevent the onset and progression of retinopathy in the presence of hypertension and related cardiovascular risk factors and diseases will also be discussed.
... Intermittent fasting has been shown to trigger substantial remodeling of the gut microbiota (29). For example, Ozkul et al. reported significant enrichment of Lachnospiraceae and Erysipelotrichaceae after fasting, which was associated with the accumulation of short-chain fatty acids (30). However, our previous study has showed enrichment for butyric acid-producing bacteria, such as Clostridium_XlVa and Lachnospiraceae incertae sedis, before Ramadan fasting rather than after. ...
The human gut microbiota has been proposed to serve as a multifunctional organ in host metabolism, contributing effects to nutrient acquisition, immune response, and digestive health. Fasting during Ramadan may alter the composition of gut microbiota through changes in dietary behavior, which ultimately affects the contents of various metabolites in the gut. Here, we used liquid chromatography–mass spectrometry-based metabolomics to investigate the composition of fecal metabolites in Chinese and Pakistani individuals before and after Ramadan fasting. Principal component analysis showed distinct separation of metabolite profiles among ethnic groups as well as between pre- and post-fasting samples. After Ramadan fasting, the Chinese and Pakistani groups showed significant differences in their respective contents of various fecal metabolites. In particular, L-histidine, lycofawcine, and cordycepin concentrations were higher after Ramadan fasting in the Chinese group, while brucine was enriched in the Pakistani group. The KEGG analysis suggested that metabolites related to purine metabolism, 2-oxocarboxylic acid metabolism, and lysine degradation were significantly enriched in the total subject population pre-fasting vs. post-fasting comparisons. Several bacterial taxa were significantly correlated with specific metabolites unique to each ethnic group, suggesting that changes in fecal metabolite profiles related to Ramadan fasting may be influenced by associated shifts in gut microbiota. The fasting-related differences in fecal metabolite profile, together with these group-specific correlations between taxa and metabolites, support our previous findings that ethnic differences in dietary composition also drive variation in gut microbial composition and diversity. This landscape view of interconnected dietary behaviors, microbiota, and metabolites contributes to the future development of personalized, diet-based therapeutic strategies for gut-related disorders.
... Interest in the effects of TRF on gut microbiome composition and health extend beyond those interested in weight loss or therapeutic intervention. For example, individuals who observe Ramadan, during which the participants fast from sun up to sun down for 29 days, exhibit increased alpha and beta diversity, as well as changes in the abundance of several major phyla [37][38][39]. Specifically, alterations in Lachnospiraceae abundance were observed in one of these groups, which may help prevent some of the deleterious aspects of the aging process through enhancing butyrate production [40]. ...
Both ketogenic diets (KD) and time-restricted feeding (TRF) regimens have the ability to influence several parameters of physical health, including gut microbiome composition and circulating cytokine concentration. Moreover, both of these dietary interventions prevent common impairments associated with the aging process. However, significantly altering macronutrient intake, which is required for a KD, may be unappealing to individuals and decrease compliance to dietary treatments. In contrast to a KD, TRF allows individuals to continue eating the foods they are used to, and only requires a change in the time of day at which they eat. Therefore, we investigated both a KD and a diet with a more Western-like macronutrient profile in the context of TRF, and compared both diets to animals allowed access to standard chow ad libitum in young adult and aged rats. While limited effects on cytokine levels were observed, both methods of microbiome analysis (16S sequencing and metagenomics) indicate that TRF and KDs significantly altered the gut microbiome in aged rats. These changes were largely dependent on changes to feeding paradigm (TRF vs. ad libitum) alone regardless of macronutrient content for many gut microbiota, but there were also macronutrient-specific changes. Specifically, functional analysis indicates significant differences in several pathways, including those involved in the tricarboxylic acid (TCA) cycle, carbohydrate metabolism and neurodegenerative disease. These data indicate that age- and disease-related gut dysbiosis may be ameliorated through the use of TRF with both standard diets and KDs.
... They also have increased microbial richness and diversity and increased levels of the beneficial short-chain fatty acid, butyricacid-producing Lachnospiraceae. High concentrations of Lachnospiraceae are associated with a reduced risk of cancer, improved inflammatory bowel disease, better mental health, reduced allergies, and improved cardiorespiratory health [75][76][77]. ...
Obesity is a disease defined by an elevated body mass index (BMI), which is the result of excessive or abnormal accumulation of fat. Dietary intervention is fundamental and essential as the first-line treatment for obese patients, and the main rule of every dietary modification is calorie restriction and consequent weight loss. Intermittent energy restriction (IER) is a special type of diet consisting of intermittent pauses in eating. There are many variations of IER diets such as alternate-day fasting (ADF) and time-restricted feeding (TRF). In the literature, the IER diet is known as an effective method for bodyweight reduction. Furthermore, IER diets have a beneficial effect on systolic or diastolic pressure, lipid profile, and glucose homeostasis. In addition, IER diets are presented as being as efficient as a continuous energy restriction diet (CER) in losing weight and improving metabolic parameters. Thus, the IER diet could present an alternative option for those who cannot accept a constant food regimen.
... Food intake alters the inherent diurnal rhythm of the intestinal microbiome, the food content itself and feeding times play a key role in this process. 15,16 IF promotes browning of white adipose tissue and decreases obesity through modification of the intestinal microflora. 17 Timerestricted feeding contributes to the decrease of various obesogenic microorganisms and increases the proliferation of bacteria with protective functions against obesity. ...
The aim of this review is to provide an overview of the present association between Intermittent Fasting (IF), the Gut Microbiota (GM), and the adipocyte with respect to Metabolic Health (MH). A search was carried out through Dialnet, Scielo, Web of Science, Redalyc and PubMed, using keywords such as: "intermittent fasting", "time-restricted feeding", "gut microbiota" and "Metabolic Health". Intermittent fasting (IF) regimens promote weight loss, therefore contributing to improved metabolic health. IF beneficially participates in the modulation of the intestinal microbiome, allowing a continuous interaction with nutrients to be digested and shaping the intestinal immune responses during the development of cardiovascular disease, blood pressure and diabetes mellitus through metabolic activities.
... According to the positive results of pre-clinical studies, in recent years, various human studies have evaluated the association between intestinal microbiome and fasting. In some human studies, fasting diet of Ramadan type on intestinal microbiome has been evaluated (13,(36)(37)(38)(39). The duration of fasting time was 12-18 h per day in these studies. ...
Background
In recent years, intermittent fasting (IF) has gained popularity in the health and wellness in the world. There are numerous types of IF, all of which involve fasting periods that last longer than an overnight fast and involve limited meal time-windows, with or without calorie restriction. The objective of this review is to summarize the current evidence for the effects of Ramadan and non-Ramadan IF on gut microbiome.
Methods
We explored PubMed, Scopus, Web of Science, and Google Scholar according to the PRISMA criteria (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Animal and human studies were screened and reviewed separately by two researchers.
Results
Twenty-eight studies were selected after screening. Some of the studies were performed on animal models and some on humans. The results of these studies indicate a significant shift in the gut microbiota, especially an increase in the abundance of Lactobacillus and Bifidobacteria following fasting diets. The results of some studies also showed an increase in the bacterial diversity, decrease inflammation and increased production of some metabolites such as short-chain fatty acids (SCFAs) in individuals or samples under fasting diets. Moreover, Ramadan fasting, as a kind of IF, improves health parameters through positive effects on some bacterial strains such as Akkermansia muciniphila and Bacteroide . However, some studies have reported adverse effects of fasting diets on the structure of the microbiome.
Conclusion
In general, most studies have seen favorable results following adherence from the fasting diets on the intestinal microbiome. However, because more studies have been done on animal models, more human studies are needed to prove the results.
... Ozkul et al. [69] hypothesized that RF might lead to changes in gut microbial composition and diversity. A total of nine adult subjects were included in the study. ...
The medical literature on health aspects of Ramadan fasting (RF) is widely spread in many journals of varying access, making it less readily available to those interested in the subject. We performed a nonsystematic review of the international literature from a major online database (PubMed in 1 year [2020]). The search term “Ramadan fasting” was used, and relevant literature was narrated in a concise thematic account excluding diabetes. The publications spanned fundamental, clinical, ethical, professional, cultural, and advocacy facets. The publications predictably crossed the conventional disciplinary lines and geographical locations and appeared in journals with different access systems. The contents are presented under the emerged themes depending on the retrieved literature. This year, the basic coverage included changes in physiology, nutrition during Ramadan. However, the clinical issues included a more comprehensive range such as the impact of RF on the liver and gut, and endocrine conditions such as hypothyroidism and adrenal insufficiency. Coverage also included chronic kidney disease, maternal health and fetal well-being, cardiovascular medicine, nature and function of eyes, and neurological conditions, especially epilepsy. Sports medicine and athletes' well-being received somewhat prominent coverage. Other researchers focused on documenting patients' and health-care professionals' perceptions, attitudes, and practices during Ramadan. Health aspects of RF received a sustained academic interest with a broad spectrum in 2020. This narrative provides a scoping overview to help researchers and clinicians catch up quickly with state-of-the-art science today.
... In fact, dietary habit is well-established as the main factor affecting gut microbiota structure and function (David et al., 2014). In terms of the effects of fasting behavior on gut microbiota, Ozkul, Yalinay, and Karakan (2020) reported that fasting can lead to shifts in gut microbial community composition. More recently, Ali et al. (2021) concluded that RIF and ethnicity, which are strongly mediated by dietary changes, can alter the gut microbiota of humans. ...
This research aimed to assess the effects of Ramadan intermittent fasting (RIF) on different dimensions, namely calorie intake, fullness and hunger sensations, mental health, body weight, waist circumference (WC), quality of sleep, body composition, hydration and nutritional status among female students at the University of Bahrain. A prospective single cohort study was conducted on 20 female students. The measurements were taken before Ramadan as well as the end of each week of Ramadan. From baseline to the end of Ramadan, there was a significant decrease in body weight (−0.779 kg, CI95% −1.287, −0.271), fat mass (FM) (−1.735 kg, CI95% −2.349, −1.122) and WC (−2.158 cm, CI95% −3.902, −0.414). In addition, the Hydragram® showed an increase at week 4 (0.288% CI95% 0.72, 0.504) and nutritional status with Nutrigram® increased during the time (Ptrend <0.001). No changes were detected for anxiety status, hunger and fullness sensations and quality of sleep. The decrease in weight positively affected the loss of FM (r = 0.597), and the increase in the Pittsburgh sleep quality index affected the reduction of FM (r= −0.460). The Ptrend<0.01 for visual analogue scales and WC showed a clear effect of time on these outcomes. The findings of this study suggest potential benefits of RIF on cardiovascular and metabolic health.
... The specific effect of Ramadan fasting on the gut microbiome has not been extensively studied. A pilot study (N=9) from Turkey revealed that that microbial richness was significantly increased at the end of the Ramadan fasting period; no significant differences were found in terms of phylogenetic diversity metrics [56]. Studies in model organisms, such as mice, support the findings in humans and highlight the important changes that can occur to gut microbiota when fasting is conducted. ...
INTRODUCTION
The Ramadan fast (RF) entails a major shift from the normal ways of eating to an exclusive
nocturnal eating pattern. In this form of intermittent fasting, multiple modulations of the human body physiology may occur [1]. These changes can induce or alter pathophysiological states depending on the pre-existing state of the disease and the individual’s compliance to diet, lifestyle, and therapeutic regimens [2].
During Ramadan, individuals that fast tend to avoid consulting their doctors [3]. It is therefore not surprising that potentially invasive studies have been difficult to conduct, leading to a relative paucity of direct evidence regarding the physiological effects of the RF. Obtaining evidence for guidelines can be problematic; it is very difficult to ask individuals to volunteer for Ramadan related research studies at a time of spiritual focus and when there is an anticipation of breaking the fast in family union and obligations to attend religious practices in the feeding hours. Studies can also take longer to complete as Ramadan occurs only once a year, so there is a small window of opportunity to collect information.
Much of the insight gained to date has been extrapolated from studies involving subjects who have fasted for more than 48 hours. However, recently, many more studies of the RF have been conducted, with new and updated evidence emerging on different aspects of physiology during Ramadan and these will be discussed in this chapter. The chapter will be presented in four sections: Physiology, Pathophysiology in Diabetes, and Pathophysiology of the RF in other conditions, particularly those commonly encountered in people with diabetes.
... We used 16S rRNA gene sequences of type strains obtained from the RDP database as it allows the option to download the bulk dataset [19]. Three different databases were used for microbiome analysis, namely Greengenes, SILVA, and EzTaxon [20] which used for 16S rRNA gene-based microbiome studies [21][22][23][24][25][26]. Although several different analysis pipeline alternatives like Dada2, QIIME 2, deblur are currently avalilable, we chose QIIME 1 pipeline as it is well accepted by scientific community having over 22000 citations and being used globally for microbiome analysis [27-36]. 1 97_d_ez 4486 3609 2 97_d_gg 4486 3609 3 97_d_silva 4486 3609 4 97_c_ez 4789 3752 5 97_c_gg 4486 3609 6 97_c_silva 4699 3699 7 99_d_gg 5650 4733 8 99_d_silva 5650 4733 9 99_c_gg 5687 4743 10 99_c_silva 5643 ...
16S rRNA gene analysis is the most convenient and robust method for microbiome studies. Inaccurate taxonomic assignment of bacterial strains could have deleterious effects as all downstream analyses rely heavily on the accurate assessment of microbial taxonomy. The use of mock communities to check the reliability of the results has been suggested. However, often the mock communities used in most of the studies represent only a small fraction of taxa and are used mostly as validation of sequencing run to estimate sequencing artifacts. Moreover, a large number of databases and tools available for classification and taxonomic assignment of the 16S rRNA gene make it challenging to select the best-suited method for a particular dataset. In the present study, we used authentic and validly published 16S rRNA gene type strain sequences (full length, V3-V4 region) and analyzed them using a widely used QIIME pipeline along with different parameters of OTU clustering and QIIME compatible databases. Data Analysis Measures (DAM) revealed a high discrepancy in ratifying the taxonomy at different taxonomic hierarchies. Beta diversity analysis showed clear segregation of different DAMs. Limited differences were observed in reference data set analysis using partial (V3-V4) and full-length 16S rRNA gene sequences, which signify the reliability of partial 16S rRNA gene sequences in microbiome studies. Our analysis also highlights common discrepancies observed at varioustaxonomic levels using various methods and databases.
... Ramadan is associated with intermittent fasting for a substantial proportion of humankind (∼20% of the world population), and similar forms of intermittent fasting exist for other important religious faiths as well. Nevertheless, the effects of such altered dietary intake patterns on gut microbiome have not yet been well characterized, but a preliminary study did document shifts in microbiota in Ramadanadhering participants (24). Importantly, it is recognized that religion-inspired intermittent fasting provokes similar beneficial effects on physiology compared with other forms of intermittent fasting (25). ...
Background
Intermittent fasting is a popular dietary intervention with perceived relatively easy compliance and is linked to various health benefits, including weight loss and improvement in blood glucose concentrations. The mechanistic explanations underlying the beneficial effects of intermittent fasting remain largely obscure but may involve alterations in the gut microbiota.
Objectives
We sought to establish the effects of 1 mo of intermittent fasting on the gut microbiome.
Methods
We took advantage of intermittent fasting being voluntarily observed during the Islamic faith-associated Ramadan and sampled feces and blood, as well as collected longitudinal physiologic data in 2 cohorts, sampled in 2 different years. The fecal microbiome was determined by 16S sequencing. Results were contrasted to age- and body weight–matched controls and correlated to physiologic parameters (e.g., body mass and calorie intake).
Results
We observed that Ramadan-associated intermittent fasting increased microbiome diversity and was specifically associated with upregulation of the Clostridiales order–derived Lachnospiraceae [no fasting 24.6 ± 13.67 compared with fasting 39.7 ± 15.9 in relative abundance (%); linear discriminant analysis = 4.9, P < 0.001 by linear discriminant analysis coupled with effect size measurements] and Ruminococcaceae [no fasting 13.4 ± 6.9 compared with fasting 23.2 ± 12.9 in relative abundance (%); linear discriminant analysis = 4.7, P < 0.001 by linear discriminant analysis coupled with effect size measurements] bacterial families. Microbiome composition returned to baseline upon cessation of intermittent feeding. Furthermore, changes in Lachnospiraceae concentrations mirrored intermittent fasting–provoked changes in physiologic parameters.
Conclusions
Intermittent fasting provokes substantial remodeling of the gut microbiome. The intermittent fasting–provoked upregulation of butyric acid–producing Lachnospiraceae provides an obvious possible mechanistic explanation for health effects associated with intermittent fasting.
... We used 16S rRNA gene sequences of type strains obtained from the RDP database as it allows the option to download the bulk dataset [19]. Three different databases were used for microbiome analysis, namely Greengenes, SILVA, and EzTaxon [20] which used for 16S rRNA gene-based microbiome studies [21][22][23][24][25][26]. Although several different analysis pipeline alternatives like Dada2, QIIME 2, deblur are currently avalilable, we chose QIIME 1 pipeline as it is well accepted by scientific community having over 22000 citations and being used globally for microbiome analysis [27-36]. 1 97_d_ez 4486 3609 2 97_d_gg 4486 3609 3 97_d_silva 4486 3609 4 97_c_ez 4789 3752 5 97_c_gg 4486 3609 6 97_c_silva 4699 3699 7 99_d_gg 5650 4733 8 99_d_silva 5650 4733 9 99_c_gg 5687 4743 10 99_c_silva 5643 ...
16S rRNA gene analysis is the most convenient and robust method for microbiome studies. Inaccurate taxonomic assignment of bacterial strains could have deleterious effects as all downstream analyses rely heavily on the accurate assessment of microbial taxonomy. The use of mock communities to check the reliability of the results has been suggested. However, often the mock communities used in most of the studies represent only a small fraction of taxa and are used mostly as validation of sequencing run to estimate sequencing artifacts. Moreover, a large number of databases and tools available for classification and taxonomic assignment of the 16S rRNA gene make it challenging to select the best-suited method for a particular dataset. In the present study, we used authentic and validly published 16S rRNA gene type strain sequences (full length, V3-V4 region) and analyzed them using a widely used QIIME pipeline along with different parameters of OTU clustering and QIIME compatible databases. Data Analysis Measures (DAM) revealed a high discrepancy in ratifying the taxonomy at different taxonomic hierarchies. Beta diversity analysis showed clear segregation of different DAMs. Limited differences were observed in reference data set analysis using partial (V3-V4) and full-length 16S rRNA gene sequences, which signify the reliability of partial 16S rRNA gene sequences in microbiome studies. Our analysis also highlights common discrepancies observed at various taxonomic levels using various methods and databases.
... Indeed, fasting/feeding intervals notwithstanding, time of eating can alter bacterial abundance and function (10), which could disrupt circadian rhythmicity and negatively impact the GM. In a follow-up study to Özkul et al. (102), a broader microbial community analysis was conducted on samples from the same participants using a 16S sequencing approach (104). There were significant increases in microbial richness and butyrate-producing bacteria, including Butyricicoccus, Faecalibacterium, and Roseburia genus phylogenetic level. ...
Calorie restriction is a primary dietary intervention demonstrated over many decades in cellular and animal models to modulate aging pathways, positively affect age-associated diseases, and, in clinical studies, to promote beneficial health outcomes. Because long-term compliance with daily calorie restriction has proven problematic in humans several intermittent fasting (IF) regimens, including alternate day fasting (ADF) and time-restricted feeding (TRF), have evolved revealing similar clinical benefits as calorie restriction. Despite significant research on the cellular and physiological mechanisms contributing to, and responsible for, these observed benefits, relatively little research has investigated the impact of these various fasting protocols on the gut microbiome (GM). Reduced external nutrient supply to the gut may beneficially alter the composition and function of a 'fed' gut microflora. Indeed, the prevalent, obesogenic Western diet can promote deleterious changes in the GM, signaling intermediates involved in lipid and glucose metabolism, and immune responses in the gastrointestinal tract. This review describes recent preclinical and clinical effects of varying fasting regimens on GM composition and associated physiology. Although the number of preclinical and clinical interventions are limited, significant data thus far suggest fasting interventions impact GM composition and physiology. However, there are considerable heterogeneities of study design, methodological considerations, and practical implications. Ongoing research on the health impact of fasting regimes on GM modulation is warranted.
... The gut microbiome also helps stimulate host immunity, regulate pathogen growth (e.g., competitive exclusion), synthesize essential amino acids, and provides other health outcomes (Krajmalnik-Brown et al., 2012;Honda and Littman, 2016;Gentile and Weir, 2018;Li et al., 2018;Valdes et al., 2018), including improving responsiveness to chemotherapy (Mager et al., 2020). Cultural habits (Sonnenburg and Sonnenburg, 2019;Ozkul et al., 2020), seasonal variability (Smits et al., 2017), geography (De Filippo et al., 2010), and individual lifestyle preferences (Dahl et al., 2020;Pittman, 2020) influence the structure, function, and diversity of the gut microbiome. This is demonstrated by the striking differences in microbiome composition between hunter-gatherer and agricultural societies; societies that typically consume diets with high and low levels of microbial accessible carbohydrates, respectively (Jha et al., 2018;Sonnenburg and Sonnenburg, 2019). ...
The human diet is temporally and spatially dynamic, and influenced by culture, regional food systems, socioeconomics, and consumer preference. Such factors result in enormous structural diversity of ingested glycans that are refractory to digestion by human enzymes. To convert these glycans into metabolizable nutrients and energy, humans rely upon the catalytic potential encoded within the gut microbiome, a rich collective of microorganisms residing in the gastrointestinal tract. The development of high-throughput sequencing methods has enabled microbial communities to be studied with more coverage and depth, and as a result, cataloging the taxonomic structure of the gut microbiome has become routine. Efforts to unravel the microbial processes governing glycan digestion by the gut microbiome, however, are still in their infancy and will benefit by retooling our approaches to study glycan structure at high resolution and adopting next-generation functional methods. Also, new bioinformatic tools specialized for annotating carbohydrate-active enzymes and predicting their functions with high accuracy will be required for deciphering the catalytic potential of sequence datasets. Furthermore, physiological approaches to enable genotype-phenotype assignments within the gut microbiome, such as fluorescent polysaccharides, has enabled rapid identification of carbohydrate interactions at the single cell level. In this review, we summarize the current state-of-knowledge of these methods and discuss how their continued development will advance our understanding of gut microbiome function.
A considerable portion of the world's population practices fasting, for religious purposes like Ramadan or to adopt a healthier lifestyle such as intermittent fasting. During this period, individuals undergo metabolic changes that alter their internal environment. The literature was analysed to identify a possible relationship between fasting and the development of Helicobacter pylori-induced peptic ulcers. This found that fasting does not affect the incidence of peptic ulcers, and studies that saw an increase in the incidence were not significant. However, remodelling of the gastric environment and increases in concentrations of H. pylori were recorded. There is no relationship between fasting and the risk of developing H. pylori-induced peptic ulcers, suggesting that individuals with uncomplicated ulcers are not at risk of developing further ulcers and can participate in fasts provided they take the recommended measures.
Obesity often results in severe negative health consequences and represents a growing issue for global health. Reducing food intake is a crucial factor for weight loss. Intermittent fasting is a relatively new intervention that contributes to weight reduction. Considering the intimate relationship between obesity and inflammatory pathologies with gut microbiota alterations, a systematic review of the literature was herein conducted to elucidate the relationship between time-restricted food intake and gut microbiota diversity in humans. Searches are carried out in three databases (PubMed, MedLine/OVID, and Academic Search Complete) between April 2019 and April 2022. Nine studies (all with longitudinal design) were identified as eligible by presenting data about the impact of intermittent fasting schemes on gut microbiota. At the phylum level, Firmicutes and Bacteroidetes increase throughout follow-ups, while 16 bacteria genera change their abundance in response to intermittent fasting. Finally, some genera associated with clinical predictors such as weight change, abdominal circumference, and metabolic variables were reported. Changes induced by fasting schemes positively impact the diversity and abundance of gut microbiota and the biomarkers described here. However, the changes previously reported have been studied in short periods and some return to their basal state after fasting intervention.
Each individual has a unique gut microbiota; therefore the genes in our microbiome out-number the genes in our genome by about 150 to 1. Perturbation in host nutritional status influences gut microbiome composition and vice versa. The gut microbiome can help in producing vitamins, hormones, and other active metabolites that support the immune system; harvest energy from food; aid in digestion; protect against pathogens; improve gut transit and function; send signals to the brain and other organs, oscillating the circadian rhythm and coordinate with host metabolism through multiple cellular pathways. Gut microbiota can be influenced by host genetics, medications, diet, and lifestyle factors from preterm to aging. Aligning to precision nutrition, identifying personalized microbiome mandates the provision of the right nutrients at right time to the right patient. So before prescribing a personalized treatment, it is crucial to monitor and count the gut flora as a focused biomarker. Many nutritional approaches that have been developed help in maintaining and restoring an optimal microbiome such as specific diet therapy, nutrition interventions and customized eating patterns. One of these approaches is time-restricted feeding/eating (TRF/E), a type of intermittent fasting (IF) in which a subject abstains from food intake for a specific time window. Such a dietary modification might alter and restore the gut microbiome for proper alignment of cellular and molecular pathways throughout the lifespan. In this review, we have highlighted that gut microbiota would be a targeted biomarker and TRF/E would be a targeted approach for restoring the gut microbiome-associated molecular pathways like hormonal signaling, the circadian system, metabolic regulators, neural responses, and immune-inflammatory pathways. Consequently, modulation of gut microbiota through TRF/E could contribute to the proper utilization and availability of nutrients and confer protection against diseases by harnessing personalized nutrition approaches to improve human health.
Religious fasting is practiced by people of all faiths, including Christianity, Islam, Buddhism, Jainism, as well as Hinduism, Judaism, and Taoism. Individual/clinical, public, global, and planetary health has traditionally been studied as separate entities. Nevertheless, religious fasting, in conjunction with other religious health assets, can provide several opportunities, ranging from the individual to the population, environmental, and planetary levels, by facilitating and supporting societal transformations and changes, such as the adoption of healthier, more equitable, and sustainable lifestyles, therein preserving the Earth's systems and addressing major interconnected, cascading, and compound challenges. In this review, we will summarize the most recent evidence on the effects of religious fasting, particularly Orthodox and Ramadan Islamic fasting, on human and public health. Further, we will explore the potential effects of religious fasting on tackling current environmental issues, with a special focus on nutrition/food restriction and planetary health. Finally, specific recommendations, particularly around dietary intake during the fasting rituals, will be provided to ensure a sustainable healthy planet.
Experimental trials in organisms ranging from yeast to humans have shown that various forms of reducing food intake (caloric restriction) appear to increase both overall and healthy lifespan, delaying the onset of disease and slowing the progression of biomarkers of aging. The gut microbiota is considered one of the key environmental factors strongly contributing to the regulation of host health. Perturbations in the composition and activity of the gut microbiome are thought to be involved in the emergence of multiple diseases. Indeed, many studies investigating gut microbiota have been performed and have shown strong associations between specific microorganisms and metabolic diseases including overweight, obesity, and type 2 diabetes mellitus as well as specific gastrointestinal disorders, neurodegenerative diseases, and even cancer. Dietary interventions known to reduce inflammation and improve metabolic health are potentiated by prior fasting. Inversely, birth weight differential host oxidative phosphorylation response to fasting implies epigenetic control of some of its effector pathways. There is substantial evidence for the efficacy of fasting in improving insulin signaling and blood glucose control, and in reducing inflammation, conditions for which, additionally, the gut microbiota has been identified as a site of both risk and protective factors. Accordingly, human gut microbiota, both in symbiont and pathobiont roles, have been proposed to impact and mediate some health benefits of fasting and could potentially affect many of these diseases. While results from small-N studies diverge, fasting consistently enriches widely recognized anti-inflammatory gut commensals such as Faecalibacterium and other short-chain fatty acid producers, which likely mediates some of its health effects through immune system and barrier function impact.
Background and aims
There is a large body of research focused on various aspects related to Ramadan intermittent fasting (RIF) and human health and disease. This study aimed to quantify the bibliometric data of RIF medical research over the past seven decades and explore these variables qualitatively via text mining analysis.
Methods
We used the Scopus search engine to identify published articles related to RIF from inception to December 31, 2021. All types of research articles were included. Scientometric and bibliometric measures were determined using Excel, Biblioshiny, and VOSviewer. This study proposed a bibliometric and text mining method to qualitatively and quantitatively recognize the RIF research trend.
Results
The Scopus search returned 1916 relevant articles. Most citations pertained to publications from the last two decades, and most publications were original research articles. These publications had received around 27,000 citations, and the 20 most prolific publishing journals had an average h-index of 112.25. More than one-third of all medical publications were in open-access journals. There was a 13-fold increase in medical research on RIF over the past few decades. We identified the 10 most prolific publishing countries, institutes, journals, and authors. We also identified five scientific hotspots of RIF scientific literature, which were: diabetes, metabolic health, public health, physiology, and maternity.
Conclusion
This is the first comprehensive bibliometric analysis of medical research related to RIF. The research gaps identified will shape future research directions and foster collaborative research activities toward enhanced medical nutrition research revolving around RIF.
There is a large body of research focused on various aspects related to Ramadan intermittent fasting (RIF) and human health and disease. This study aimed to quantify the bibliometric parameters of RIF medical research over the past seven decades and explore these parameters qualitatively via text mining analysis. We used the Scopus search engine to identify published articles related to RIF from inception to December 31, 2021. All types of research articles were included. Scientometric and bibliometric parameters were determined using Excel, Biblioshiny, and VOSviewer. The Scopus search returned 1916 relevant articles. Most citations pertained to publications from the last two decades, and most publications were original research articles. These publications had received around 27,000 citations, and the 20 most prolific publishing journals had an h-index of 112.25. More than one-third of all medical publications were in open-access journals. There was a 13-fold increase in medical research on RIF over the past few decades. We identified the 10 most prolific publishing countries, institutes, journals, and authors. This is the first comprehensive bibliometric analysis of medical research related to RIF. The research gaps identified will inform future research directions and foster collaborative research activities.
Aims
This study aimed to evaluate the effects of Ramadan diurnal intermittent fasting (RDIF; 29–30 days) on cardiometabolic risk factors (CMRF) in healthy adults, and examine the effect of various cofactors on the outcomes using sub-group meta-regression.
Data synthesis
We conducted a systematic review and meta-analysis to measure the effect sizes of changes in CMRF in healthy adult Muslims observing RDIF. Ten scientific databases (EBSCOhost, CINAHL, Cochrane, EMBASE, PubMed/MEDLINE, Scopus, Google Scholar, ProQuest Medical, ScienceDirect, and Web of Science) were searched from the date of inception (1950) to the end of November 2020. The CMRF searched and analyzed were total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), diastolic blood pressure (DBP), and heart rate (HR). We identified 91 studies (4431 adults aged 18–85 years) conducted between 1982 and 2020 in 23 countries distributed over four continents. RDIF-induced effect sizes for CMRF were: TC (no. of studies K=77, number of subjects N=3705, Hedge’s g=−0.092, 95% confidence interval (CI): −0.168, 0.016); TG (K=74, N=3591, Hedge’s g=−0.127, 95% CI: −0.203, 0.051); HDL-C (K=68, N=3528, Hedge’s g=0.141, 95% CI: 0.053, 0.228); LDL-C (K=65, N=3354, Hedge’s g= −0.118, 95% CI: −0.201, 0.035); VLDL-C (K=13, N=648, Hedge’s g=−0.252, 95% CI: −0.431, 0.073), DBP (K=32, N=1716, Hedge’s g=−0.255, 95% CI: −0.363, 0.147), and HR (K=12, N=674, Hedge’s g=−0.082, 95% CI: −0.300, 0.136). Meta-regression revealed that the age of the fasting people was the significant moderator for changes in both HDL-C (P=0.02) and VLDL-C (P=0.01), while male sex was the only significant moderator for changes in LDL-C (P=0.055). The fasting time duration was the only significant moderator for HDL-C (P=0.001) at the end of Ramadan.
Conclusions
RDIF positively impacts CMRF, which may confer short-term transient protection against cardiovascular disease among healthy people.
Fasting and especially intermittent fasting have been shown to be an effective intervention in many diseases, such as obesity and diabetes. The fasting-mimicking diet (FMD) has recently been found to ameliorate metabolic disorders. To investigate the effect of a new type of low-protein low-carbohydrate FMD on diabetes, we tested an FMD in db/db mice, a genetic model of type 2 diabetes. The diet was administered every other week for a total of 8 weeks. The intermittent FMD normalized blood glucose levels in db/db mice, with significant improvements in insulin sensitivity and β cell function. The FMD also reduced hepatic steatosis in the mice. Deterioration of pancreatic islets and the loss of β cells in the diabetic mice were prevented by the FMD. The expression of β cell progenitor marker Ngn3 was increased by the FMD. In addition, the FMD led to the reconstruction of gut microbiota. Intermittent application of the FMD increased the genera of Parabacteroides and Blautia while reducing Prevotellaceae, Alistipes and Ruminococcaceae. The changes in these bacteria were also correlated with the fasting blood glucose levels of the mice. Furthermore, intermittent FMD was able to reduce fasting blood glucose level and increase β cells in STZ-induced type 1 diabetic mouse model. In conclusion, our study provides evidence that the intermittent application of an FMD is able to effectively intervene in the progression of diabetes in mice.
Electronic supplementary material
The online version of this article (10.1186/s12986-018-0318-3) contains supplementary material, which is available to authorized users.
Intermittent fasting (IF) protects against the development of metabolic diseases and cancer, but whether it can prevent diabetic microvascular complications is not known. In db/db mice, we examined the impact of long-term IF on diabetic retinopathy (DR). Despite no change in glycated hemoglobin, db/db mice on the IF regimen displayed significantly longer survival and a reduction in DR endpoints, including acellular capillaries and leukocyte infiltration. We hypothesized that IF mediated changes in the gut microbiota would produce beneficial metabolites and prevent the development of DR. Microbiome analysis revealed increased levels of Firmicutes and decreased Bacteroidetes and Verrucomicrobia Compared to db/db mice on ad-libitum (AL) feeding, changes in the microbiome of the db/db mice on IF were associated with increases in gut mucin, goblet cell number and villi length and reductions in plasma peptidoglycan. Consistent with the known modulatory effects of Firmicutes on bile acid (BA) metabolism, measurement of BAs demonstrated a significant increase of tauroursodeoxycholate (TUDCA), a neuroprotective BA, in db/db on IF but not in db/db on AL feeding. TGR-5, the TUDCA receptor, was found in neural cells of the retina primary ganglion cells. Expression of TGR5 did not change with IF or diabetes. However, IF reduced retinal TNF-α mRNA, which is a key downstream target of TGR-5 activation. Pharmacological activation of TGR5 using INT-767 prevented DR in a second diabetic mouse model. These findings support the concept that IF prevents DR by restructuring the microbiota towards species producing TUDCA and subsequent retinal protection by TGR5 activation.
Fecal microbiota transplantation (FMT) is now widely used to treat recurrent Clostridium difficile infection, but has been less studied as a means to restore microbiome diversity and composition following antibiotic or chemotherapy treatments. The purpose of our study was to assess the efficacy of FMT to reverse antibiotic- and chemotherapy-induced gut dysbiosis in a mouse model. C57BL/6J mice were treated with ampicillin for 1 week and/or received a single intraperitoneal injection of 5-Fluorouracil. Fresh stool was collected and analyzed using shotgun metagenomics and the Illumina sequencing platform. Ampicillin caused a significant and immediate decrease in bacterial species richness and diversity that persisted for one week. In mice that received FMT, disruption of the intestinal microbiota was reversed immediately. Antibiotic and chemotherapy administration caused significant alteration in species distribution, including a decrease in the relative proportions of Clostridium scindens and Faecalibacterium prausnitzii, and an increase in known pathogenic species. In mice receiving FMT, we observed a significant increase in species known to exhibit anti-inflammatory properties. Moreover, chemotherapy led to a critical decrease in key 'health-promoting' species and to an altered functional profile, especially when chemotherapy was administered in tandem with antibiotics, and that FMT can ameliorate these effects.
The management of the dysbiosed gut microbiota in inflammatory bowel diseases (IBD) is gaining more attention as a novel target to control this disease. Probiotic treatment with butyrate-producing bacteria has therapeutic potential since these bacteria are depleted in IBD patients and butyrate has beneficial effects on epithelial barrier function and overall gut health. However, studies assessing the effect of probiotic supplementation on microbe-microbe and host-microbe interactions are rare. In this study, butyrate-producing bacteria (three mono-species and one multispecies mix) were supplemented to the fecal microbial communities of ten Crohn’s disease (CD) patients in an in vitro system simulating the mucus- and lumen-associated microbiota. Effects of supplementation in short-chain fatty acid levels, bacterial colonization of mucus environment and intestinal epithelial barrier function were evaluated. Treatment with F. prausnitzii and the mix of six butyrate-producers significantly increased the butyrate production by 5–11 mol%, and colonization capacity in mucus- and lumen-associated CD microbiota. Treatments with B. pullicaecorum 25-3T and the mix of six butyrate-producers improved epithelial barrier integrity in vitro. This study provides proof-of-concept data for the therapeutic potential of butyrate-producing bacteria in CD and supports the future preclinical development of a probiotic product containing butyrate-producing species.
An impaired gut microbiota has been reported as an important factor in the pathogenesis of obesity. Weight reduction has already been mentioned to improve gut microbial subpopulations involved in inflammatory processes, though other subpopulations still need further investigation. Thus, weight reduction in the context of a fasting program together with a probiotic intervention may improve the abundance and diversity of gut microbiota.
In this pilot study, overweight people underwent a fasting program with laxative treatment for 1 week followed by a 6 week intervention with a probiotic formula. Gut microbiota were analyzed on the basis of 16s rDNA with a quantitative real time polymerase chain reaction. Additionally, a food frequency questionnaire with questions about nutritional behavior, lifestyle, and physical activity was administered before and after the intervention.
We observed an increase in microbial diversity over the study period. No significant changes in abundance of total bacteria, or of Bacteroidetes, Prevotella, Clostridium cluster XIVa, or Clostridium cluster IV were found, although Faecalibacterium prausnitzii showed an increase over the study period. In addition, Akkermanisa and Bifidobacteria increased in abundance due to intervention. The inflammation-associated gut microbes Enterobacteria and Lactobacilli increased during the first week and then declined by the end of the intervention. Two-thirds of the study participants harbored Archaea. No significant improvements of eating habits were reported, although physical activity improved due to the intervention.
Our results show that caloric restriction affects gut microbiota by proliferating mucin-degrading microbial subpopulations. An additional intervention with a probiotic formula increased probiotic-administered gut microbial populations.
We aimed to assess the effect of Islamic intermittent fasting, during and outside of Ramadan, on plasma levels of leptin and ghrelin while controlling for several potential confounding variables. Eight healthy male volunteers with a mean age of 26.6±4.9 years reported to the sleep disorders center (SDC) at King Saud University on four occasions: 1) adaptation; 2) 4 weeks before Ramadan while performing Islamic fasting for 1 week (baseline fasting) (BLF); 3) 1 week before Ramadan (non-fasting baseline) (BL); and 4) during the second week of Ramadan while fasting. Plasma leptin and ghrelin levels were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00. During BLF, there were significant reductions in plasma leptin concentrations at 22:00 and 02:00 compared with the baseline concentrations (at 22:00: 194.2±177.2 vs. 146.7±174.5; at 02:00: 203.8±189.5 vs. 168.1±178.1; p<0.05). During Ramadan, there was a significant reduction in plasma leptin levels at 22:00 (194.2±177.2 vs. 132.6±130.4, p<0.05). No significant difference in plasma ghrelin concentrations was detected during the BL, BLF, or Ramadan periods. Cosinor analyses of leptin and ghrelin plasma levels revealed no significant changes in the acrophases of the hormones during the three periods. The nocturnal reduction in plasma leptin levels during fasting may be the result of the changes in meal times during fasting.
Bacteria play an important role in the onset and perpetuation of intestinal inflammation in inflammatory bowel disease (IBD). Unlike in Crohn's disease (CD), in which dysbiosis has been better characterised, in ulcerative colitis (UC), only small cohorts have been studied and showed conflicting data. Therefore, we evaluated in a large cohort if the microbial signature described in CD is also present in UC, and if we could characterise predominant dysbiosis in UC. To assess the functional impact of dysbiosis, we quantified the bacterial metabolites.
The predominant microbiota from 127 UC patients and 87 age and sex-matched controls was analysed using denaturing gradient gel electrophoresis (DGGE) analysis. Differences were quantitatively validated using real-time PCR. Metabolites were quantified using gas chromatography-mass spectrometry.
Based on DGGE analysis, the microbial signature previously described in CD was not present in UC. Real-time PCR analysis revealed a lower abundance of Roseburia hominis (p<0.0001) and Faecalibacterium prausnitzii (p<0.0001) in UC patients compared to controls. Both species showed an inverse correlation with disease activity. Short-chain fatty acids (SCFA) were reduced in UC patients (p=0.014), but no direct correlation between SCFA and the identified bacteria was found.
The composition of the fecal microbiota of UC patients differs from that of healthy individuals: we found a reduction in R hominis and F prausnitzii, both well-known butyrate-producing bacteria of the Firmicutes phylum. These results underscore the importance of dysbiosis in IBD but suggest that different bacterial species contribute to the pathogenesis of UC and CD.
Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.
Obesity is associated with complications during pregnancy and increased health risks in the newborn. The objective of the present study was to establish possible relationships between gut microbiota, body weight, weight gain and biochemical parameters in pregnant women. Fifty pregnant women were classified according to their BMI in normal-weight (n 34) and overweight (n 16) groups. Gut microbiota composition was analysed by quantitative real-time PCR in faeces and biochemical parameters in plasma at 24 weeks of pregnancy. Reduced numbers of Bifidobacterium and Bacteroides and increased numbers of Staphylococcus, Enterobacteriaceae and Escherichia coli were detected in overweight compared with normal-weight pregnant women. E. coli numbers were higher in women with excessive weight gain than in women with normal weight gain during pregnancy, while Bifidobacterium and Akkermansia muciniphila showed an opposite trend. In the whole population, increased total bacteria and Staphylococcus numbers were related to increased plasma cholesterol levels. Increased Bacteroides numbers were related to increased HDL-cholesterol and folic acid levels, and reduced TAG levels. Increased Bifidobacterium numbers were related to increased folic acid levels. Increased Enterobacteriaceae and E. coli numbers were related to increased ferritin and reduced transferrin, while Bifidobacterium levels showed the opposite trend. Therefore, gut microbiota composition is related to body weight, weight gain and metabolic biomarkers during pregnancy, which might be of relevance to the management of the health of women and infants.
Immunological dysregulation is the cause of many non-infectious human diseases such as autoimmunity, allergy and cancer. The gastrointestinal tract is the primary site of interaction between the host immune system and microorganisms, both symbiotic and pathogenic. In this Review we discuss findings indicating that developmental aspects of the adaptive immune system are influenced by bacterial colonization of the gut. We also highlight the molecular pathways that mediate host-symbiont interactions that regulate proper immune function. Finally, we present recent evidence to support that disturbances in the bacterial microbiota result in dysregulation of adaptive immune cells, and this may underlie disorders such as inflammatory bowel disease. This raises the possibility that the mammalian immune system, which seems to be designed to control microorganisms, is in fact controlled by microorganisms.
Obesity is a major public health issue as it enhances the risk of suffering several chronic diseases of increasing prevalence. Obesity results from an imbalance between energy intake and expenditure, associated with a chronic low-grade inflammation. Gut microbes are considered to contribute to body weight regulation and related disorders by influencing metabolic and immune host functions. The gut microbiota as a whole improves the host's ability to extract and store energy from the diet leading to body weight gain, while specific commensal microbes seem to exert beneficial effects on bile salt, lipoprotein, and cholesterol metabolism. The gut microbiota and some probiotics also regulate immune functions, protecting the host form infections and chronic inflammation. In contrast, dysbiosis and endotoxaemia may be inflammatory factors responsible for developing insulin resistance and body weight gain. In the light of the link between the gut microbiota, metabolism, and immunity, the use of dietary strategies to modulate microbiota composition is likely to be effective in controlling metabolic disorders. Although so far only a few preclinical and clinical trials have demonstrated the effects of specific gut microbes and prebiotics on biological markers of these disorders, the findings indicate that advances in this field could be of value in the struggle against obesity and its associated-metabolic disorders.
The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).
A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been observed repeatedly in Crohn disease (CD) patients. In this study, we determined the composition of the mucosa-associated microbiota of CD patients at the time of surgical resection and 6 months later using FISH analysis. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CD. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-κB activity, F. prausnitzii had no effect on IL-1β-induced NF-κB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-γ production levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis, as demonstrated by real-time quantitative PCR (qPCR) analysis. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-κB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment.
• IBD
• microbiota
• probiotic
The diversity of mucin-degrading bacteria in the human intestine was investigated by combining culture and 16S rRNA-dependent approaches. A dominant bacterium, strain MucT, was isolated by dilution to extinction of faeces in anaerobic medium containing gastric mucin as the sole carbon and nitrogen source. A pure culture was obtained using the anaerobic soft agar technique. Strain MucT was a Gram-negative, strictly anaerobic, non-motile, non-spore-forming, oval-shaped bacterium that could grow singly and in pairs. When grown on mucin medium, cells produced a capsule and were found to aggregate. Strain MucT could grow on a limited number of sugars, including N-acetylglucosamine, N-acetylgalactosamine and glucose, but only when a protein source was provided and with a lower growth rate and final density than on mucin. The G + C content of DNA from strain MucT was 47.6 mol%. 16S rRNA gene sequence analysis revealed that the isolate was part of the division Verrucomicrobia. The closest described relative of strain MucT was Verrucomicrobium spinosum (92 % sequence similarity). Remarkably, the 16S rRNA gene sequence of strain MucT showed 99 % similarity to three uncultured colonic bacteria. According to the data obtained in this work, strain MucT represents a novel bacterium belonging to a new genus in subdivision 1 of the Verrucomicrobia; the name Akkermansia muciniphila gen. nov., sp. nov. is proposed; the type strain is MucT (= ATCC BAA-835T = CIP 107961T).
New therapeutic targets for noncognitive reductions in energy intake, absorption, or storage are crucial given the worldwide epidemic of obesity. The gut microbial community (microbiota) is essential for processing dietary polysaccharides. We found that conventionalization of adult germ-free (GF) C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. Studies of GF and conventionalized mice revealed that the microbiota promotes absorption of monosaccharides from the gut lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is selectively suppressed in the intestinal epithelium of normal mice by conventionalization. Analysis of GF and conventionalized, normal and Fiaf knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor and that its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. Studies of Rag1-/- animals indicate that these host responses do not require mature lymphocytes. Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host.
• symbiosis
• nutrient processing
• energy storage
• adiposity
• fasting-induced adipose factor
Germ-free mice were maintained on polysaccharide-rich or simple-sugar diets and colonized for 10 days with an organism also found in human guts, Bacteroides thetaiotaomicron, followed by whole-genome transcriptional profiling of bacteria and mass spectrometry of cecal glycans. We found that these bacteria assembled on food particles and mucus, selectively induced outer-membrane polysaccharide-binding proteins and glycoside hydrolases, prioritized the consumption of liberated hexose sugars, and revealed a capacity to turn to host mucus glycans when polysaccharides were absent from the diet. This flexible foraging behavior should contribute to ecosystem stability and functional diversity.
We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that, in this model, obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals.
• energy balance/obesity
• host-microbial interactions
• intestinal bacterial diversity
• ob/ob mice
• phylogenetics
While intermittent or periodic fasting provides a variety of favorable health benefits, the molecular mediators of these effects are poorly understood. In this issue of Cell Metabolism, Li and colleagues (2017) highlight the role of gut microbiota in mediating benefits of intermittent fasting through activation of adipose tissue beiging. While intermittent or periodic fasting provides a variety of favorable health benefits, the molecular mediators of these effects are poorly understood. In this issue of Cell Metabolism, Li and colleagues highlight the role of gut microbiota in mediating benefits of intermittent fasting through activation of adipose tissue beiging.
While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases.
The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits. Expected final online publication date for the Annual Review of Nutrition Volume 37 is August 21, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Over the last decade, our appreciation for the contribution of resident gut microorganisms—the gut microbiota—to human health has surged. However, progress is limited by the sheer diversity and complexity of these microbial communities. Compounding the challenge, the majority of our commensal microorganisms are not close relatives of Escherichia coli or other model organisms and have eluded culturing and manipulation in the laboratory. In this Review, we discuss how over a century of study of the readily cultured, genetically tractable human gut Bacteroides has revealed important insights into the biochemistry, genomics and ecology that make a gut bacterium a gut bacterium. While genome and metagenome sequences are being produced at breakneck speed, the Bacteroides provide a significant ‘jump-start’ on uncovering the guiding principles that govern microbiota–host and inter-bacterial associations in the gut that will probably extend to many other members of this ecosystem.
The genus Roseburia consists of obligate Gram-positive anaerobic bacteria that are slightly curved, rod-shaped and motile by means of multiple subterminal flagella. It includes five species: Roseburia intestinalis, R. hominis, R. inulinivorans, R. faecis and R. cecicola. Gut Roseburia spp. metabolize dietary components that stimulate their proliferation and metabolic activities. They are part of commensal bacteria producing short-chain fatty acids, especially butyrate, affecting colonic motility, immunity maintenance and anti-inflammatory properties. Modification in Roseburia spp. representation may affect various metabolic pathways and is associated with several diseases (including irritable bowel syndrome, obesity, Type 2 diabetes, nervous system conditions and allergies). Roseburia spp. could also serve as biomarkers for symptomatic pathologies (e.g., gallstone formation) or as probiotics for restoration of beneficial flora.