No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
The Gut Microbiome and Its Role in Obesity
Abstract
The human body is host to a vast number of microbes, including bacterial, fungal, and protozoal microorganisms, which together constitute our microbiota. Evidence is emerging that the intestinal microbiome is intrinsically linked with overall health, including obesity risk. Obesity and obesityrelated metabolic disorders are characterized by specific alterations in the composition and function of the human gut microbiome. Mechanistic studies have indicated that the gastrointestinal microbiota can influence both sides of the energy balance equation, namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Moreover, its composition is not fixed and can be influenced by several dietary components. This fact raises the attractive possibility that manipulating the gut microbiota could facilitate weight loss or prevent obesity in humans. Emerging as possible strategies for obesity prevention and/or treatment are targeting the microbiota to restore or modulate its composition through the consumption of live bacteria (probiotics), nondigestible or limited digestible food constituents such as oligosaccharides (prebiotics), or both (synbiotics) or even fecal transplants.
... This enzyme is present in the liver and muscle fibers and serves as a cellular energy indicator. Inhibition of AMPK causes a reduction in fatty acid oxidation and, as a result, an increase in fat storage [118][119][120]. The gut bacteria may potentially play a role in metabolic abnormalities in obesity by causing systemic inflammation. ...
... Lipopolysaccharides from the gut microbiota bind Tolllike receptors (primarily Toll-Like receptor 4; TLR4) in the cell membrane of Gram-negative bacteria. TLRs are well-known immunological transmembrane proteins that govern inflammatory responses' origin, size, and duration by upregulating inflammatory cytokines and chemokines and engaging intracellular signaling pathways [118][119][120]. Obese people have greater short-chain fatty acid levels and fewer leftover meal calories in their stools than lean people [118][119][120]. ...
... TLRs are well-known immunological transmembrane proteins that govern inflammatory responses' origin, size, and duration by upregulating inflammatory cytokines and chemokines and engaging intracellular signaling pathways [118][119][120]. Obese people have greater short-chain fatty acid levels and fewer leftover meal calories in their stools than lean people [118][119][120]. Despite all of the data, there are still gaps in our understanding of the function of gut microbiota in obesity development and how treatment of the microbiota might help control the disease. ...
Obesity has recently emerged as one of the most severe health concerns. It is a key autonomous risk factor for heart failure and contributes to cardiovascular disease (CVD) risk factors such as hypertension, type 2 diabetes, and metabolic abnormalities. Obesity is caused by a metabolic imbalance, which occurs when calories burnt are fewer than the number of calories consumed. There are several pathways accountable for the adverse impacts of obesity on the cardiovascular system. Inflammatory cell infiltration develops in the adipose tissue, the pancreas, and other issues similar to the progression of obesity. Inflammation is triggered by immune cells that invade dysfunctional adipose tissue. The atherosclerotic inflammation phase, related to obesity, induces coronary calcification. Obesity is linked to elevated levels of leptin and high blood pressure. Leptin causes systemic vasoconstriction, sodium retention, and increased blood pressure by influencing the synthesis of nitric oxide and activating the sympathetic nervous system. Obesity is a well-known risk factor for CVD and is one of the leading causes of the greater risk of diseases, including dyslipidemia, hypertension, depression, metabolic syndrome, atrial fibrillation, and heart failure in adults and children. When used with dietary improvements, antiobesity drugs improve the probability of experiencing clinically healthy (5%) weight loss. This review aimed to address the consequences of obesity on cardiac structure and function, risk factors, the impact of the obesity paradox, pharmacological treatment strategies for managing and recommended exercise and diet.
... Collectively, these results suggest that the healthy pediatric gut microbiome harbors compositional and functional aspects that differ from similarly matched healthy adults, and that the gut microbiome may undergo a more prolonged development than previously anticipated [67]. Therefore, childhood and adolescence may provide opportunities for microbiome interventions to promote health or prevent obesity, since the developing microbiome plays a more definitive role in establishing metabolic pathways involved with energy regulation [73][74][75][76][77]. ...
... Prebiotics must also meet three criteria: (1) resistance to gastric acid, bile, and digestive enzymes; (2) ability to undergo fermentation by gut microbiota; and (3) ability to stimulate the growth and/or activity of commensal gut microbiota [91]. Gut hormones such as GLP-1 play a critical role in relaying signals of nutritional and energy status from the gut to the central nervous system to control food intake [76]. GLP-1 is upregulated by prebiotics, suggesting that prebiotics may be used to control food intake [76]. ...
... Gut hormones such as GLP-1 play a critical role in relaying signals of nutritional and energy status from the gut to the central nervous system to control food intake [76]. GLP-1 is upregulated by prebiotics, suggesting that prebiotics may be used to control food intake [76]. Nicolucci et al. illustrated that the prebiotic of an oligofructose-enriched inulin selectively altered the intestinal microbiota, and significantly reduced body weight z-score in children with overweight and obesity compared to placebo [92]. ...
Obesity affects 42.4% of adults and 19.3% of children in the United States. Childhood obesity drives many comorbidities including hypertension, fatty liver disease, and type 2 diabetes mellitus. Prior research suggests that aberrant compositional development of the gut microbiome, with low-grade inflammation, precedes being overweight. Therefore, childhood may provide opportunities for interventions that shape the microbiome to mitigate obesity-related diseases. Children with obesity have gut microbiota compositional and functional differences, including increased proinflammatory bacterial taxa, compared to lean controls. Restoration of the gut microbiota to a healthy state may ameliorate conditions associated with obesity and help maintain a healthy weight. Pediatric bariatric (weight-loss) surgery is an effective treatment for childhood obesity; however, there is limited research into the role of the gut microbiome after weight-loss surgery in children. This review will discuss the magnitude of childhood obesity, the importance of the developing microbiome in establishing metabolic pathways, interventions such as bariatric surgery that may modulate the gut microbiome, and future directions for the potential development of microbiome-based therapeutics to treat obesity.
... Mounting evidence supports the notion that gut microbiota is a key modulator of host metabolism and might contribute to the development of metabolic diseases [7]. Obesity (accumulation of an excessive amount of body fat) and type-2 diabetes (impairment in the regulation and usage of glucose as an energy source due to insulin resistance) are the main metabolic disorders linked with the gut microbiome. ...
... Obesity (accumulation of an excessive amount of body fat) and type-2 diabetes (impairment in the regulation and usage of glucose as an energy source due to insulin resistance) are the main metabolic disorders linked with the gut microbiome. For instance, compared to conventional murine models, germ-free mice are protected from calorie-dense dietinduced obesity [7]. Therefore, rewiring the gut microbiota represents a new avenue for tackling various metabolic disorders [8]. ...
... Therefore, rewiring the gut microbiota represents a new avenue for tackling various metabolic disorders [8]. An effective strategy to modulate the gut microbiota is the administration of probiotics, defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host" [7,8]. Probiotic treatment ameliorates weight gain in animals fed a high-fat diet (HFD) [9,10]. ...
Overconsumption of highly refined carbohydrates contributes significantly to the current obesity pandemics. Probiotic administration protects against weight gain in animals fed a high-fat diet (HFD). Nonetheless, the anti-obesity effects of probiotics in a high-carbohydrate diet (HCD)-induced obesity models are not well elucidated. Herein, C57BL/6N male mice were fed an HCD (70% kcal carbohydrate) for 12 weeks and were orally treated with multi-strain probiotics (MSPs) at 1010 CFU or saline every day for 6 weeks. MSPs contained Lactobacillus acidophilus DSM 24936, Lactiplantibacillus plantarum DSM 24937, and Limosilactobacillus reuteri DSM 25175. MSPs treatment not only ameliorated weight gain but also modulated the body fat composition altered by HCD. The MSPs also attenuated the expression of adipogenesis- and lipogenesis-related genes in HCD-fed mice. In addition, MSPs promoted the expression of lipolysis- and fatty acid oxidation-promoting factors in HCD-fed mice. Furthermore, MSPs modulated the expression of thermogenesis-related genes and the serum levels of obesity-related hormones altered by HCD. Treatment with MSPs positively reversed the Firmicutes/Bacteroidetes ratio, which is associated with a risk of obesity. Hence, this study explores the multifaceted anti-obesity mechanisms of MSPs and highlights their potential to be used as effective weight-management products.
... Some types of diets, like the Western diet, can modify microbiota, especially by increasing Firmicutes levels, leading to dysbiosis, metabolic stress, and obesity [174,175]. Compared to the Western diet, a diet based on dietary fiber, plant polysaccharides, and lower fat and animal protein is characterized by a lower level of Firmicutes and a higher level of Bacteroidetes [28,176]. Importantly, some mice and human studies underlined that a high-fat/highsugar Western diet can modify the microbiota in just 1 day [177,178]. ...
... The obesity-microbiota relationship and its mechanisms have been studied for a long time [168] Many studies have shown that alterations in the microbiota community modify the process of energy extraction from food and consequently the adiposity of the body [176]. The gut microbiota of obese people has a larger capacity for absorbing energy from meals, thus their gut bacteria lead to weight growth [170]. ...
Microbiomics represents a new science studying the microbiome, consisting of all the microorganisms of a given community. This new science collects data about all the members of the microbial community and quantifies the molecules responsible for the structure, function, and dynamics of the microbiome. The human microbiome plays a very important role in the healthy state and in a variety of disease states. The human microbiome knowledge has evolved during the last decades and nowadays one can consider that, in particular, the gut microbiota is seen as a significant organ holding 150 times more genes compared to the human genome. This chapter will focus on discussing the normal and modified phyla and species of the gut microbiome in a variety of conditions, providing a better understanding of host-microbiome interactions. We will highlight some new associations between intestinal dysbiosis and acute or chronic inflammatory and metabolic diseases.
... The gut microbiome sustains the body's metabolism and energy balance. It can increase the accumulation of adipose tissue in the host [24] and contribute to obesity in different ways [25]. A gut microbiome study was also conducted as it is strongly associated with obesity and could be influenced by the mulberry leaf supplements provided in the current research. ...
... Gut microbiome is also a crucial factor contributing to both anti-obesity and antiinflammatory properties [25,46]. Therefore, microbiome analysis was also performed to study the gut microbiome in the studied animals, and the differential abundance of the gut microbiome in the treatment groups. ...
Overweight and obesity, associated with various health complications, refer to abnormal or excessive fat accumulation conditions that harm health. Like humans, obesity is a growing problem in dogs, which may increase the risk of serious diseases such as diabetes and cancer. Mulberry leaf has shown potential anti-obesity and anti-diabetes effects in several studies. Our research studied the impact of mulberry leaf supplements in healthy old overweight dogs for 12 weeks. Blood and fecal samples were collected from the dogs before and after treatment for different analyses, including whole transcriptome and gut microbiome analysis. The Body Condition Score (BCS) and blood glucose levels were significantly decreased in all mulberry treatment groups, which justifies the anti-obesity effect of mulberry leaf in dogs. Throughout the whole transcriptome study, the downregulation of PTX3 and upregulation of PDCD-1, TNFRSF1B, RUNX3, and TICAM1 genes in the high mulberry group were found, which have been associated with anti-inflammatory effects in the literature. It may be an essential gene expression mechanism responsible for the anti-inflammatory and, subsequently, anti-obesity effects associated with mulberry leaf treatment, as confirmed by real-time polymerase chain reaction analysis. In microbiome analysis, Papillibacter cinnamivorans, related to the Mediterranean diet, which may cause anti-inflammatory effects, were abundant in the same treatment group. Further studies may be required to establish the gene expression mechanism and role of abundant bacteria in the anti-obesity effect of mulberry supplements in dogs. Overall, we propose mulberry leaves as a portion of food supplements for improving blood glucose levels and the anti-inflammation of blood in companion dogs.
... Research has shown that alterations of the gut microbiome or the presence of certain pathologically relevant species can be associated with vitamin deficiency [2], obesity [3], inflammatory bowel diseases [4] and colon cancer [5], and autoimmune [6] and neurodegenerative disorders [7]. The microbiome is an intensively researched field, but the relevance of many factors still remains to be fully explained and it is uncertain to what extent the intestinal flora is influenced by genetic factors or environmental conditions (diet, sport, etc.) [8]. ...
Microbiomic analysis of human gut samples is a beneficial tool to examine the general well-being and various health conditions. The balance of the intestinal flora is important to prevent chronic gut infections and adiposity, as well as pathological alterations connected to various diseases. The evaluation of microbiome data based on next-generation sequencing (NGS) is complex and their interpretation is often challenging and can be ambiguous. Therefore, we developed an innovative approach for the examination and classification of microbiomic data into healthy and diseased by visualizing the data as a radial heatmap in order to apply deep learning (DL) image classification. The differentiation between 674 healthy and 272 type 2 diabetes mellitus (T2D) samples was chosen as a proof of concept. The residual network with 50 layers (ResNet-50) image classification model was trained and optimized, providing discrimination with 96% accuracy. Samples from healthy persons were detected with a specificity of 97% and those from T2D individuals with a sensitivity of 92%. Image classification using DL of NGS microbiome data enables precise discrimination between healthy and diabetic individuals. In the future, this tool could enable classification of different diseases and imbalances of the gut microbiome and their causative genera.
... Similarly, obese patients who were put on a lowfat or low-carbohydrate diet for at least a year had less Firmicutes in their colon and more Bacteroidetes. As a result, such research suggests that lifestyle changes, such as dietary changes, does affect gut microbiota [16,41]. ...
The interaction between the gut microbiota and its mammalian host is influenced by diet. The host can absorb small metabolites produced by the microbiota, which can alter a range of physiological processes. Several types of gut microbes are linked to immunological and metabolic illnesses, as well as the host's overall health. Bacteroides, Clostridium, and Bifidobacterium are frequently found among these gut flora. We look at how the human intestinal microbiome is influenced by nutrition obtained from plant or animal based diet and how this can affect health and disease. Anaerobic bacteria in the colon produce short chain fatty acids (SCFAs) as the principal metabolic products of fermentation. As possible mediators, these fatty acids have been connected to the gut microbiota's influence on intestinal immune function. They've also been implicated in the treatment of inflammatory disorders such as obesity, type 2 diabetes, and heart disease. To this end, the Mediterranean diet (MD), as compared to a westernized diet, has more dietary fibre, leading to the generation of SCFAs. MD thus, has a favourable impact on the immune system and gut bacteria. As a result, the Mediterranean diet is encouraged not only as a potential aid in the treatment of numerous ailments, but also as a means of promoting global health.
... Our findings appear to be consistent with previous studies. The ratio of Firmicutes to Bacteroidetes at the phylum level is considered to be a biomarker for obesity ( [48], [49]). Increases in physical training of rats has led to an increase in their levels of Synergistetes [50]. ...
The microbiome plays a key role in the health of the human body. Interest often lies in finding features of the microbiome, alongside other covariates, which are associated with a phenotype of interest. One important property of microbiome data, which is often overlooked, is its compositionality as it can only provide information about the relative abundance of its constituting components. Typically, these proportions vary by several orders of magnitude in datasets of high dimensions. To address these challenges we develop a Bayesian hierarchical linear log-contrast model which is estimated by mean field Monte-Carlo coordinate ascent variational inference (CAVI-MC) and easily scales to high dimensional data. We use novel priors which account for the large differences in scale and 1 constrained parameter space associated with the compositional covariates. A reversible jump Monte Carlo Markov chain guided by the data through univariate approximations of the variational posterior probability of inclusion, with proposal parameters informed by approximating variational densities via auxiliary parameters, is used to estimate intractable marginal expectations. We demonstrate that our proposed Bayesian method performs favourably against existing frequentist state of the art compositional data analysis methods. We then apply the CAVI-MC to the analysis of real data exploring the relationship of the gut microbiome to body mass index.
... Links between obesity and gut microbiota have been discussed a lot [204]. Evidence suggested that dysbiosis may contribute to the onset and pathogenesis of obesity. ...
In recent years, research on the interaction between flavonoids and intestinal microbes have prompted a rash of food science, nutriology and biomedicine, complying with future research trends. The gut microbiota plays an essential role in the maintenance of intestinal homeostasis and human health, but once the intestinal flora dysregulation occurs, it may contribute to various diseases. Flavonoids have shown a variety of physiological activities, and are metabolized or biotransformed by gut microbiota, thereby producing new metabolites that promote human health by modulating the composition and structure of intestinal flora. Herein, this review demonstrates the key notion of flavonoids as well as intestinal microbiota and dysbiosis, aiming to provide a comprehensive understanding about how flavonoids regulate the diseases by gut microbiota. Emphasis is placed on the microbiota-flavonoid bidirectional interaction that affects the metabolic fate of flavonoids and their metabolites, thereby influencing their metabolic mechanism, biotransformation, bioavailability and bioactivity. Potentially by focusing on the abundance and diversity of gut microbiota as well as their metabolites such as bile acids, we discuss the influence mechanism of flavonoids on intestinal microbiota by protecting the intestinal barrier function and immune system. Additionally, the microbiota-flavonoid bidirectional interaction plays a crucial role in regulating various diseases. We explain the underlying regulation mechanism of several typical diseases including gastrointestinal diseases, obesity, diabetes and cancer, aiming to provide a theoretical basis and guideline for the promotion of gastrointestinal health as well as the treatment of diseases.
... The microbiota can influence both aspects of the energy balance of the host organism; namely, as a factor affecting energy harvest from the diet and as a factor influencing host genes affecting the deposition of energy (e.g., fasting-induced adipocyte factor), regulating energy expenditure and storage. Gut microbiota composition is characterised by constant variability, and it can be influenced by several dietary components, such as probiotics, including fermented foods, or prebiotics, such as inulin, other oligosaccharides, lactulose, and resistant starch, suggesting the possibility that manipulation of the gut microbiota may promote weight loss or prevent obesity in humans [17]. ...
Obesity is a rapidly growing problem of public health on a worldwide scale, responsible for more than 60% of deaths associated with high body mass index. Recent studies underpinned the augmenting importance of the gut microbiota in obesity. Gut microbiota alterations affect the energy balance of the host organism; namely, as a factor affecting energy production from the diet and as a factor affecting host genes regulating energy expenditure and storage. Gut microbiota composition is characterised by constant variability, and is affected by several dietary factors, suggesting the probability that manipulation of the gut microbiota may promote leaning or prevent obesity. Our narrative review summarizes the results of recent years that stress the effect of gut microbiota in the development of obesity. It investigates the factors (diet, dietary components, lifestyle, and environment) that might affect the gut microbiota composition. Possible strategies for the prevention and/or treatment of obesity include restoring or modifying the composition of the microbiota by consuming prebiotics and probiotics, fermented foods, fruits, vegetables, and avoiding foods of animal origin high in saturated fat and sugar.
... Similarly, consumption of the fermented milk, rich in Lactobacillus rhamnosus NCDC 17, significantly reduce the body weight, epididymal fat mass, fasting blood glucose levels and serum insulin levels in mice fed with a fat-rich diet [92]. Apart from beneficial bacteria, the consumption of yeasts (Saccharomyces boulardii), promote healthy gut microbiota such as the Bacteroidetes and simultaneously decrease the Firmicutes, resulting in a steep decline in host adiposity and circulating inflammatory markers [93]. ...
Our planet is facing a wide range of inevitable and unprecedented changes such as, the water and food scarcity to the natural calamities, namely flooding, droughts and rising sea levels. All these global challenges had been addressed through the Sustainable Development Goals (SDGs) drafted by the general assembly of the United Nations. In light of the current population growth, it is difficult to attain the sustainable development using conventional and non-renewable natural resources by remaining within the planetary boundaries of Earth. In order to maintain the environment and ecological integrity, the utilization of renewable living natural resources such as microbes become inevitable. Due to their roles in geo physio-chemical processes and bioenergy transformations, microbes allow 'cradle-to-cradle' model of development using wastewater as a renewable resource. The circular wastewater economy is the sole sustainable method to achieve the SDGs of providing clean water and the sanitation to address the issue of water insecurity. The review presents an inter-connected overview on the roles and functions performed by the prokaryotic (bacteria) and eukaryotic (algae and fungi) microorganisms, which are crucial for attaining the environment sustainability within the planetary boundaries. Apart from the environmental roles of microbes, the review also highlights the importance of human-microbe interactions (gut microbiome) and edible microbial species (algae and fungi) which are essential for developing sustainable future alternatives to human nutrition, well being and prevention of diseases.
... For instance, the microbiota of obese patients typically contains a higher abundance of bacteria belonging to the Firmicutes group, and fewer Bacteroidetes. 2 This could be because Western diets lack certain nutrients that are essential in supporting a healthy gut microbiota, like dietary fibre for instance that is mostly found in fruits, vegetables and wholegrain cereals. The absence of microbiota-friendly nutrients from our diet can affect our gut bacteria until compromising the mutual relationship that we normally maintain with them. ...
As rising obesity rates threaten to overwhelm healthcare services, physicians still lack efficacious therapies to halt the cardiovascular complications of the disease. The gut microbiota – a whole community of microorganisms that resides in our intestine – has recently emerged as major player in human health. Crucially, the gut microbes are extremely dependant on our dietary habits, and promote both health and disease. In obese patients, the gut microbiota is found to be profoundly altered, which is believed to promote disease complications including cardiovascular disorders. On the other hand, the preservation of a healthy gut microbiota has protective effects against obesity-related complications, which can be promoted by certain diets. Consequently, understanding the relationship between diet, the gut microbiota, and our body could help physicians to develop new strategies for preventing cardiac diseases in obese patients.
... As discussed above, obesity is the key event in the development of metabolic syndrome [7,8]. Strong evidence links obesity to altered colonic microbiota [125]. Obese men show increased intestinal Firmicutes:Bacteroidetes ratio compared to people with normal body weight [126]. ...
Today’s sedentary lifestyle with too much food and too little exercise has made metabolic syndrome a pandemic. Metabolic syndrome is a major risk factor for type-2 diabetes and cardiovascular disease. New knowledge of medical and nutraceutical intervention in the early stages of metabolic syndrome is central to prevent these deadly complications. People who eat chili pepper on a regular basis seem to stay healthier and live longer than those who do not. Animal experiments suggest a therapeutic potential for dietary capsaicin, the active principle in hot chili pepper, to reduce the risk of developing metabolic syndrome. This is an attractive theory since capsaicin has been a culinary staple for thousands of years, and is generally deemed safe when consumed in hedonically acceptable doses. The broad expression of the capsaicin receptor TRPV1 in metabolically active tissues lends experimental support to this theory. This review critically evaluates the available experimental and clinical evidence for and against dietary capsaicin being an effective dietary means to improve cardio-metabolic health. It comes to the conclusion that although a chili pepper-rich diet is associated with a reduced risk of dying due to cardiovascular disease, dietary capsaicin has no clear effect on blood glucose or lipid profiles. Therefore, the reduced mortality risk may reflect the beneficial action of digested capsaicin on gut microbiota.
... The intestinal microbiota is essential for regulating homeostasis in the human immune and metabolic systems [26][27][28] . The disturbance of intestinal microbiota has been linked to colorectal cancer, autism, chronic diseases such as heart disease, respiratory diseases, inflammatory bowel disease, obesity, and some metabolic diseases such as diabetes, liver cirrhosis, and non-alcoholic fatty liver disease [29][30][31][32][33][34][35][36][37] . Moreover, the microbiota can have an impact on the outcomes of viral diseases 38 . ...
Objective:
COVID-19 has been a major infectious disease lately in humans. 10% of people experience persistent symptoms twelve weeks after having COVID-19. The gut microbiota is essential for host immunity. Thus, gut microbiota composition may contribute to the recovery of COVID-19 patients. The impact of COVID-19 on the gut microbiota of patients during recovery is less explored. We investigated the potential alterations of bacterial gut microbiota of immediately recovered COVID-19 patients, and six months after their recovery.
Materials and methods:
Stool samples were collected from 8 patients with COVID-19 immediately after their recovery, and six months after SARS-CoV-2 clearance, as well as from 8 healthy donors as a control group. 16S rRNA gene sequencing was performed to analyze the correlation between disease recovery and microbiota using the immediately recovered and control group. Specific primers were designed for the most significantly altered bacteria and used to analyze the changes in intestinal microbiota composition of patients using qPCR. qPCR comparisons were performed on three groups: newly recovered from COVID-19, after six months of COVID-19 recovery, and healthy controls.
Results:
Compared with the healthy control group, patients who immediately recovered from COVID-19 had significantly less presence of 15 bacterial groups. The immediately recovered patients had a very significantly higher relative abundance of the opportunistic pathogen Mycolicibacterium. No differences were found between the immediately recovered patients, and after six months of recovery using the qPCR analyses.
Conclusions:
Our results contribute novel insights regarding the alteration of human gut microbiota and the emergence of opportunistic pathogens in recovered patients of COVID-19. Further studies with a larger experimental size are needed to reveal balance or dysbiosis in patients after COVID-19 recovery.
... and Enterobacteria, while the high-fat group had higher bacterial diversity, mainly including Acinetobacter spp., Enterobacteria, Flavobacterium spp., Pseudomonas spp., and Coryneforms; In the high-fat-fed mice, the content of Bacteroidetes increased significantly at 1 week, and the ratio of Firmicutes to Bacteroidetes changed from 0.86 to 1.77 after 8 weeks. At the same time, fat deposition and intestinal dysbiosis were also found, the content of Verrucobacterium was significantly increased, while the E. coli was significantly decreased (93); Recent studies have shown that fasting can reduce host serum lipid levels and improve hepatic steatosis by reducing the ratio of Firmicutes to Bacteroidetes and increasing the abundance of Allobaculum in the host, resulting in improving metabolic disorders and intestinal flora imbalance caused by high-fat diet (94). The effects of an imbalance in the host's flora reflect the problems caused by an imbalance in diet, and a balanced diet is one of the ways in which the host can ensure that all of its physiological functions are functioning properly. ...
A large number of studies have proved that biological metabolic phenotypes exist objectively and are gradually recognized by humans. Gut microbes affect the host’s metabolic phenotype. They directly or indirectly participate in host metabolism, physiology and immunity through changes in population structure, metabolite differences, signal transduction and gene expression. Obtaining comprehensive information and specific identification factors associated with gut microbiota and host metabolic phenotypes has become the focus of research in the field of gut microbes, and it has become possible to find new and effective ways to prevent or treat host metabolic diseases. In the future, precise treatment of gut microbes will become one of the new therapeutic strategies. This article reviews the content of gut microbes and carbohydrate, amino acid, lipid and nucleic acid metabolic phenotypes, including metabolic intermediates, mechanisms of action, latest research findings and treatment strategies, which will help to understand the relationship between gut microbes and host metabolic phenotypes and the current research status.
... Previous studies have indicated that the gut microbiome can affect the obesity and obesity-related metabolic disorders by regulating the energy expenditure and absorption from the diet [47,48]. The body mass index (BMI) is commonly used as a measure of classifying overweight and obesity in adults [49]. ...
Background
Comparisons of the gut microbiome of lean and obese humans have revealed that obesity is associated with the gut microbiome plus changes in numerous environmental factors, including high-fat diet (HFD). Here, we report that two species of Bifidobacterium are crucial to controlling metabolic parameters in the Korean population.
Results
Based on gut microbial analysis from 99 Korean individuals, we observed the abundance of Bifidobacterium longum and Bifidobacterium bifidum was markedly reduced in individuals with increased visceral adipose tissue (VAT), body mass index (BMI), blood triglyceride (TG), and fatty liver. Bacterial transcriptomic analysis revealed that carbohydrate/nucleoside metabolic processes of Bifidobacterium longum and Bifidobacterium bifidum were associated with protecting against diet-induced obesity. Oral treatment of specific commercial Bifidobacterium longum and Bifidobacterium bifidum enhanced bile acid signaling contributing to potentiate oxidative phosphorylation (OXPHOS) in adipose tissues, leading to reduction of body weight gain and improvement in hepatic steatosis and glucose homeostasis. Bifidobacterium longum or Bifidobacterium bifidum manipulated intestinal sterol biosynthetic processes to protect against diet-induced obesity in germ-free mice.
Conclusions
Our findings support the notion that treatment of carbohydrate/nucleoside metabolic processes-enriched Bifidobacterium longum and Bifidobacterium bifidum would be a novel therapeutic strategy for reprograming the host metabolic homeostasis to protect against metabolic syndromes, including diet-induced obesity.
88iFgxnB7AkxSyj5zCNySmVideo Abstract
... The gut microbiome refers to the 300-500 bacterial species inhabiting the human gastrointestinal system [20], and the dominate bacterial species are divided into three phyla: Bacteroidetes, Firmicutes, and Actinobacteria [21]. When studied in humans, obese individuals have more Firmicutes and almost 90% less Bacteroidetes than lean counterparts, and weight loss in the obese group is associated with a decrease in Firmicutes and increase in Bacteroidetes [22]. ...
The gut microbiota, also known as our “second brain” is an exciting frontier of research across a multitude of health domains. Gut microbes have been implicated in feeding behaviour and obesity, as well as mental health disorders including anxiety and depression, however their role in the development and maintenance of eating disorders (EDs) has only recently been considered. EDs are complex mental health conditions, shaped by a complicated interplay of factors. Perhaps due to an incomplete understanding of the etiology of EDs, treatment remains inadequate with affected individuals likely to face many relapses. The gut microbiota may be a missing piece in understanding the etiology of eating disorders, however more robust scientific inquiry is needed in the field before concrete conclusions can be made. In this spotlight paper, we critically evaluate what is known about the bi-directional relationship between gut microbes and biological processes that are implicated in the development and maintenance of EDs, including physiological functioning, hormones, neurotransmitters, the central nervous system, and the immune system. We outline limitations of current research, propose concrete steps to move the field forward and, hypothesize potential clinical implications of this research.
Plain English summary
Our gut is inhabited by millions of bacteria which have more recently been referred to as “our second brain”. In fact, these microbes are thought to play a role in ED behaviour, associated anxiety and depression, and even affect our weight. Recent research has dove into this field with promising findings that have the potential to be applied clinically to improve ED recovery. The present paper discusses what is known about the gut microbiome in relation to EDs and the promising implications that leveraging this knowledge, through fecal microbiome transplants, probiotics, and microbiome-directed supplemental foods, could have on ED treatment.
... This procedure resulted in the development of insulin resistance and increased fat content in germ free mice. By using 16s rRNA gene sequencing, we found evidence for obesity in these mice (Davis, 2016). The dominant phyla firmicutes and bacteroides are found to be true in humans as well. ...
Humans have co-evolved with microorganisms, which play a pivotal role in determining the overall well-being of biological systems. Evolution has made certain species of bacteria thrive in the human gut, utilising the catabolized nutrients of the host and exhibiting symbiosis. It chiefly comprises a densely populated group of microbes, collectively called the Gut Microbiota. The relationship between the human system and the gut microbiome is a very sparsely introduced subject yet managed to catch everyone's eye, just for its sheer complexity. The nature and type of microbe present in the gut vary widely with respect to socio-economic, ethnic, and geographic influences. There has been extensive study done and some are underway showcasing the potential link between the gut-microbiome and the host, humans. As amusing as the gut-microbiome it is, its relationship with the host is quite remarkable. The gut-human connection is important in metabolism, coordination (brain axis), immunity, and, of course, disease. The diseases that were known earlier have recently been known to be associated with the gut microflora. Hence, this area of gut and human health has been in the focus of researchers and scientists in recent times. In this review literature, we have tried to consolidate the health aspects of humans influenced by gut dysbiosis. A few interactions are also discussed, like metabolic activity, gut-brain axis, drug action, diet influence, and immunity. This literature is aimed at showcasing the association and complexity of the gut microbiome with human health.
... 78 Hence, the development of obesity is mainly associated with its involvement with the reduction of SCFAs, inflammatory processes, and energy regulation. 79- 81 The intestinal microbiota are also able to ferment polysaccharides present in the diet that are not digested by humans, thus generating SCFAs. 80 Once absorbed, SCFAs could be transferred to hepatocytes, where they would mediate lipogenesis and gluconeogenesis as substrates. ...
... This includes a collection of trillions of microorganisms interacting with human hosts, with effects ranging from beneficial to pathogenic (7). One of the first hypotheses about this association between microbiota and BMI proposed that certain groups of bacteria were efficient in absorbing nutrients and energy and then, through rapid metabolism of nutrients, boosting calories absorbed, leading to an increase in BMI (8). It must be considered that overgrowth of bacteria of the phylum Firmicutes, accompanied by reduction of bacteria from phylum Bacteroidetes, was a characteristic of obese mice and human intestines (9). ...
Obesity is a pathology whose incidence is increasing throughout the world. There are many pathologies associated with obesity. In recent years, the influence of the microbiota on both health and pathological states has been known. There is growing information related to changes in the microbiome and obesity, as well as its associated pathologies. Changes associated with age, exercise, and weight changes have been described. In addition, metabolic changes associated with the microbiota, bariatric surgery, and fecal matter transplantation are described. In this review, we summarize the biology and physiology of microbiota in obese patients, its role in the pathophysiology of several disorders associated, and the emerging therapeutic applications of prebiotics, probiotics, and fecal microbiota transplantation.
... 05 Khadka et al. (2021) also synthesized a prodrug of curcumin with monoglucuronide (CMG) (Figure 7), altering the gut microbiota and immune responses to treat obesity. As low fecal microbial diversity is associated with increased total fat and dyslipidemia, higher low-grade inflammation, and homeostasis, thus CMG administration could affect both the overall gut microbiome compositions and the abundance of individual bacteria in feces, ileal contents, and the ileal mucosa (Davis, 2016;Yoo et al., 2021). ...
Obesity is a leading worldwide health threat with ever-growing prevalence, it promotes the incidence of various diseases, particularly cardiovascular disease, metabolic syndrome, diabetes, hypertension, and certain cancers. Traditional Chinese Medicine (TCM) has been used to control body weight and treat obesity for thousands of years, Chinese medicinal herbs provide a rich natural source of effective agents against obesity. However, some problems such as complex active ingredients, poor quality control, and unclear therapeutic mechanisms still need to be investigated and resolved. Prodrugs provide a path forward to overcome TCM deficiencies such as absorption, distribution, metabolism, excretion (ADME) properties, and toxicity. This article aimed to review the possible prodrugs from various medicinal plants that demonstrate beneficial effects on obesity and seek to offer insights on prodrug design as well as a solution to the global obesity issues.
... In overweight/obese humans, low faecal bacterial diversity is reportedly associated with a marked increase in fat tissue dyslipidaemia, impaired glucose homoeostasis and an increased incidence of low-grade inflammation. 32 In this study, bacterial diversity increased after the intervention, especially in the AFO-202+N-163 group, which showed the highest diversity in the Shannon and Simpson indices ( figure 1). Most studies have reported that an increase in Firmicutes and a decrease in Bacteroides abundance is directly proportional to body weight gain. ...
Objective
The gut microbiome and its metabolites are influenced by age and stress and reflect the metabolism and health of the immune system. We assessed the gut microbiota and faecal metabolome in a static animal model of non-alcoholic steatohepatitis (NASH).
Design
This model was subjected to the following treatments: reverse osmosis water, AFO-202, N-163, AFO-202+N-163 and telmisartan treatment. Faecal samples were collected at 6 and 9 weeks of age. The gut microbiome was analysed using 16S ribosomal RNA sequences acquired by next-generation sequencing, and the faecal metabolome was analysed using gas chromatography-mass spectrometry.
Results
Gut microbial diversity increased greatly in the AFO-202+N-163 group. Postintervention, the abundance of Firmicutes decreased, whereas that of Bacteroides increased and was the highest in the AFO-202+N-163 group. The decrease in the abundance of Enterobacteriaceae and other Firmicutes and the abundance of Turicibacter and Bilophila were the highest in the AFO-202 and N-163 groups, respectively. Lactobacillus abundance was highest in the AFO-202+N-163 group. The faecal metabolite spermidine, which is beneficial against inflammation and NASH, was significantly decreased (p=0.012) in the N-163 group. Succinic acid, which is beneficial in neurodevelopmental and neurodegenerative diseases, was increased in the AFO-202 group (p=0.06). The decrease in fructose was the highest in the N-163 group (p=0.0007). Isoleucine and Leucine decreased with statistical significance (p=0.004 and 0.012, respectively), and tryptophan also decreased (p=0.99), whereas ornithine, which is beneficial against chronic immune-metabolic-inflammatory pathologies, increased in the AFO-202+N-163 group.
Conclusion
AFO-202 treatment in mice is beneficial against neurodevelopmental and neurodegenerative diseases, and has prophylactic potential against metabolic conditions. N-163 treatment exerts anti-inflammatory effects against organ fibrosis and neuroinflammation. In combination, these compounds exhibit anticancer activity.
... Remarkably, the effect of diet on intestinal microbiota composition has become a specific subject of research. In this regard, recent evidence from various studies of humans and mice has demonstrated that changes in gut microbiota composition may play a vital role in the development of obesity (Davis, 2016;Bouter et al., 2017;Stephens et al., 2018;Socol et al., 2022). Several gut microbiota species, called the obesogenic gut microbiota, can significantly contribute to obesity, such as Firmicutes, Bacteroidetes, Rhizobium, Lactococcus, and Clostridium . ...
The human gut possesses millions of microbes that define a complex microbial community. The gut microbiota has been characterized as a vital organ forming its multidirectional connecting axis with other organs. This gut microbiota axis is responsible for host-microbe interactions and works by communicating with the neural, endocrinal, humoral, immunological, and metabolic pathways. The human gut microorganisms (mostly non-pathogenic) have symbiotic host relationships and are usually associated with the host’s immunity to defend against pathogenic invasion. The dysbiosis of the gut microbiota is therefore linked to various human diseases, such as anxiety, depression, hypertension, cardiovascular diseases, obesity, diabetes, inflammatory bowel disease, and cancer. The mechanism leading to the disease development has a crucial correlation with gut microbiota, metabolic products, and host immune response in humans. The understanding of mechanisms over gut microbiota exerts its positive or harmful impacts remains largely undefined. However, many recent clinical studies conducted worldwide are demonstrating the relation of specific microbial species and eubiosis in health and disease. A comprehensive understanding of gut microbiota interactions, its role in health and disease, and recent updates on the subject are the striking topics of the current review. We have also addressed the daunting challenges that must be brought under control to maintain health and treat diseases.
... 47 Conversely, FMT of bacteria derived from obese mice to wildtype mice causes the wild-type to extract more calories from their food resulting in a greater increase in body fat than in mice given FMT from lean mice. 48 Hypotheses for this modulation of weight status largely revolve around the effects of SCFAs or microbially produced ethanol, all of which can impact mitochondrial function and alter energy production processes. 49 While obesity has significant impact on cardiovascular disease, resident bacteria have additionally been shown to modulate cardiovascular state independent of weight status. ...
Bacteria have been known to reside in the human gut for roughly two centuries, but their modulatory effects on host health status are still not fully characterized. The gut microbiota is known to interact with dietary components and nutrients, producing functional metabolites that may alter host metabolic processes. The majority of thoroughly researched and understood gut microbial metabolites fall into two categories: short-chain fatty acids (SCFAs) and bacterial derivatives of dietary tryptophan. Despite the heavy emphasis on these metabolites, other metabolites stemming from microbial origin have significant impacts on host health and disease states. In this narrative review, we summarize eight recent studies elucidating novel bacterial metabolites, detailing the process by which these metabolites are identified, their actions within specific categories of human health, and how diet may impact production of these metabolites. With similar future mechanistic research, a more complete picture of bacterial impact on host metabolism may be constructed.
... HFD use reduces Bacteroidetes while increasing Firmicutes. Obesity and its associated health problems are rising due to this trend (Davis, 2016). According to research, HFD consumption increases body weight and fat mass and boosts adiponectin and leptin levels (Koh, Jang, Fig. 6B. ...
Konjac glucomannan’s influence on the regulation of diabetes mellitus, hyperlipidemia, and gut microbial flora was evaluated in this study. In addition, a high-fat diet and streptozotocin were used to induce type 2 diabetes mellitus in rats. At the end of the study, we analyzed various parameters such as body weight, plasma lipid profile, insulin levels by immunohistochemistry, degree of fibrosis in the liver, protein expression of PPAR-γ and p-SREBP-1C and gut microbial changes using 16S rRNA sequencing. The results of our study suggest that KGM supplementation significantly reduced the plasma lipid profile (TC, TG, VLDL, LDL, etc.). In addition, KGM has improved insulin levels, which were visualized using immunohistochemistry. Furthermore, KGM also regulated the protein expression of key regulatory proteins of lipid metabolism PPAR-γ and p-SREBP-1C (Group 3). Similar results were seen in the groups treated with the standard drug rosiglitazone (group 4). Finally, the 16S rRNA sequencing shows that KGM contributes to gut microbiota composition alterations, and it was observed using the Simpson, Shannon, Chao-1, and actual otus indices (group 3). KGM further alters the production of beneficial SCFAs and helps host good health. Furthermore, several metabolic pathways have been activated in T2DM rats. As a result, it becomes apparent that the digestive system's microbiome will play a role in T2DM. KGM has various health advantages but is particularly useful in treating hyperlipidemia and diabetes.
... It has been observed that consuming spirulina brings about a reduction in the imbalance that exists between the genera of beneficial probiotic bacteria and the genera of natural anaerobic bacteria, particularly Bacteroides spp., Eubacterium spp., and Lactobacillus spp. [150,[162][163][164]. According to the findings of research that was conducted by Abdel-Moneim et al. [165], alcoholic spirulina extracts (methanol, acetone, and hexane) and biosynthesized Se nanoparticles (SeNPs) both possessed significant antioxidant activity and antibacterial activity. ...
... The low bacterial diversity may contribute to the pathophysiology of IBS [6]. Ahmed and his colleagues took (control group) healthy individual and they were the donors, it was surprising to include 2 obese individuals in the donor group as obesity is known by alterations in the composition and function of the gut microbiome [12]. The authors have clarified the investigations to exclude organic diseases for IBS diagnosis but those that insure the safety of FMT were not clearly declared. ...
... It has been observed that consuming spirulina brings about a reduction in the imbalance that exists between the genera of beneficial probiotic bacteria and the genera of natural anaerobic bacteria, particularly Bacteroides spp., Eubacterium spp., and Lactobacillus spp. [150,[162][163][164]. According to the findings of research that was conducted by Abdel-Moneim et al. [165], alcoholic spirulina extracts (methanol, acetone, and hexane) and biosynthesized Se nanoparticles (SeNPs) both possessed significant antioxidant activity and antibacterial activity. ...
Spirulina is a kind of blue-green algae (BGA) that is multicellular, filamentous, and prokaryotic. It is also known as a cyanobacterium. It is classified within the phylum known as blue-green algae. Despite the fact that it includes a high concentration of nutrients, such as proteins, vitamins, minerals, and fatty acids—in particular, the necessary omega-3 fatty acids and omega-6 fatty acids—the percentage of total fat and cholesterol that can be found in these algae is substantially lower when compared to other food sources. This is the case even if the percentage of total fat that can be found in these algae is also significantly lower. In addition to this, spirulina has a high concentration of bioactive compounds, such as phenols, phycocyanin pigment, and polysaccharides, which all take part in a number of biological activities, such as antioxidant and anti-inflammatory activity. As a result of this, spirulina has found its way into the formulation of a great number of medicinal foods, functional foods, and nutritional supplements. Therefore, this article makes an effort to shed light on spirulina, its nutritional value as a result of its chemical composition, and its applications to some food product formulations, such as dairy products, snacks, cookies, and pasta, that are necessary at an industrial level in the food industry all over the world. In addition, this article supports the idea of incorporating it into the food sector, both from a nutritional and health perspective, as it offers numerous advantages.
... Recently, studies have been conducted on the role of gut microbiota in obesity and the role of natural compounds in preventing obesity by altering the gut microbiota composition [46]. We, too, examined the effect of S. thunbergii on the fecal microbiota of HFD-induced obese mice. ...
Sargassum thunbergii (Mertens ex Roth) Kuntze (ST) is a brown alga rich in indole-2-carboxaldehyde. This study aimed to investigate the anti-obesity effects of ethanol extract from ST in in vitro and in vivo models. In 3T3-L1 cells, ST extract significantly inhibited lipid accumulation in mature adipocytes while lowering adipogenic genes (C/epba and Pparg) and enhancing metabolic sensors (Ampk, Sirt1), thermogenic genes (Pgc-1a, Ucp1), and proteins (p-AMPK/AMPK and UCP1). During animal investigation, mice were administered a chow diet, a high-fat diet (HF), or an HF diet supplemented with ST extract (at dosages of 150 and 300 mg/kg bw per day) for 8 weeks (n = 10/group). ST extract administration decreased weight gain, white adipose tissue weight, LDL-cholesterol, and serum leptin levels while improving glucose intolerance. In addition, ST extract increased the expression of Ampk and Sirt1 in adipose tissue and in the liver, as well as p-AMPK/AMPK ratio in the liver, compared to HF-fed mice. The abundance of Bacteroides vulgatus and Faecalibacterium prausnitzii in the feces increased in response to ST extract administration, although levels of Romboutsia ilealis decreased compared with those in HF-fed mice. ST extract could prevent obesity in HF-fed mice via the modulation of AMPK activation and gut microbiota composition.
... Intestinal micro-organisms inhibit fiaf gene expression and increase lipid storage in white adipose tissue (WAT). GF mice showed increased expression of WAT fiaf, an inhibitor of LPL activity, in the small intestine compared with conventional mice (Davis et al. 2016). After the microbial community is regularized, fiaf expression is decreased and the LPL activity is increased, which lead to WAT lipid storage (Paul et al., 2016). ...
Intestinal microbiota is considered to play an integral role in maintaining health of host by modulating several physiological functions including nutrition, metabolism, and immunity. Accumulated data from human and animal studies indicate that intestinal microbes can affect lipid metabolism in host through various direct and indirect biological mechanisms. These mechanisms include the production of various signalling molecules by the intestinal microbiome, which exert a strong effect on lipid metabolism, bile secretion in the liver, reverse transport of cholesterol, and energy expenditure and insulin sensitivity in peripheral tissues. The present review discusses the findings of recent studies suggesting an emerging role of intestinal microbiota and its metabolites in regulating lipid metabolism and the association of intestinal microbiota with obesity. Additionally, we discuss the controversies and challenges in this research area. However, intestinal microorganisms are also affected by some external factor, which in turn influences the regulation of microbial lipid metabolism. Therefore, we also discuss the effects of probiotics, prebiotics, diet structure, exercise, and other factors on intestinal microbiological changes and lipid metabolism regulation.
Pancreatic cancer is a disorder that affects the biochemical and metabolic physiology of pancreas. It is the most intractable and lethal of all GI malignancies. Early metastatic spread and medication resistance restrict its prognosis. Because of the severe phase of the illness when diagnosed, only a minority of patients (20%) qualify for surgical resection. Therefore, there is a pressing need to find new alternative treatments for pancreatic cancer. Ten to twenty percent of human malignancies are linked to microbes, which are capable of causing carcinogenesis by inducing inflammation, evading immune destruction, and deregulating host genome stability prior to cancer development. A microbiome is an assembly of microbes and their genetic material found in a specific environment. Symbiotic relationships exist between the microbiome and its human hosts on the skin and, to a greater extent, in the gut. Many diseases, including pancreatic cancer, can be caused by a disturbance in the balance. In the human body, the microbiome provides numerous benefits to the host as it contributes to nutritional, metabolic, and immunological regulation. However, the tumorigenic pathway may be affected by the dysbiotic changes of the human microbiome, resulting in the development of pancreatic cancer. Besides affecting the tumour’s aggressiveness, this dysbiosis also has an effect on the microenvironment. It is possible to modify the composition of the gut microbiome and re-establishes its balance by the use of prebiotics, probiotics, next-generation probiotics, postbiotics, synbiotics, and faecal microbiota transfer. This chapter focuses on the relationship between human microbiome and pancreatic cancer, with an emphasis on current available literature evidence supporting the exploration of microbiome-based treatments and therapies to prevent and control pancreatic cancer.KeywordsMicrobiomePancreatic cancerProbioticSynbioticPostbioticFaecal microbiota transplantation
Anthocyanins are a subclass of flavonoids responsible for color in some fruits and vegetables with potent antioxidative capacity. During digestion, a larger proportion of dietary anthocyanins remains unabsorbed and reach the large intestine where they interact with the gut microbiota. Anthocyanins can modulate gut microbial populations to improve diversity and the proportion of beneficial populations, leading to alterations in short chain fatty acid and bile acid production. Some anthocyanins can be degraded into colonic metabolites, such as phenolic acids, which accumulate in the body and regulate a range of biological activities. Here we provide an overview of the effects of dietary anthocyanin consumption on gut microbial interactions, metabolism, and composition. Progression of chronic diseases has been strongly associated with imbalances in gut microbial populations. We therefore focus on the role of the gut microbiota as the 'mediator' that facilitates the therapeutic potential of anthocyanins against various chronic diseases, including obesity, type II diabetes, cardiovascular disease, neurodegenerative disease, inflammatory bowel disease, cancer, fatty liver disease, chronic kidney disease and osteoarthritis.
Doxycycline (Doxy) is an antibiotic, which has exhibited anti-inflammatory activity and glucose metabolism improvement. The present study was proposed to evaluate its effects on glucose metabolism and other associated processes, such as lipemia and adipogenesis, as well as, to evaluate its effects on the liver, pancreas, and aorta in subjects fed with an occidental high-fat diet (HFD). The trial followed three groups of BALB/c mice for 6 months: (1) Standard diet (SD); (2) HFD-placebo (saline solution); and (3) HFD-Doxy (10 mg/kg/day). Intrahepatic fat accumulation (steatohepatosis) and the epididymal fat pad, as well as the hepatic inflammatory infiltrate and ALT serum levels were higher in both groups with the HFD (with/without doxycycline) in comparison with the SD group. The thickness of the aorta (preclinic atherosclerosis) was significantly elevated in the HFD group with respect to the HFD + Doxy and SD group, these two being similar groups to each other. The HFD-Doxy group had pancreatic morphological parameters very similar to those of the SD group; on the contrary, the HFD group reduced the number of pancreatic islets and the number of β cells per mm2, in addition to losing large islets. The index of β cell function (∆Insulin0–30/∆Glucose0–30 ratio) was significantly higher in the HFD + Doxy group, compared to the rest of the groups.
The assembly and function of microbial communities depends on many factors including the local environment and the metabolic properties of the colonizing organisms. Chemical communications or other secreted factors also play a role and are used by different microbial strains both cooperatively and competitively. The spectrum of microbial secretions have various effects on the microbe's respective hosts, both positive and negative. Thus, characterizing the roles of microbial community members and their secretions can yield key mechanistic insights into microbiome function and can lead to new intervention strategies. Focusing on the simple, yet important functional impact of toxicity, we quantify supernatant dosage responses with image data and examine the morphological effects of microbial secretions on skin‐associated host cells. Since the diversity of microbial communities, coupled with the multiplicity of host tissues requires scalable methods, we develop and demonstrate a microfluidic device that enables high‐content screening of microbial secretion effects on adherent cell types. This article is protected by copyright. All rights reserved.
Cereal bran consumption improves gastrointestinal and metabolic health. Unprocessed cereal brans have a limited shelf-life and the presence of anti-nutrient phytochemicals. In the present study, lipids and antinutrients (flavonoids, tannin,...
Bile acids (BAs) serve as physiological detergents that enable the intestinal absorption and transportation of nutrients, lipids and vitamins. BAs are primarily produced by humans to catabolize cholesterol and play crucial roles in gut metabolism, microbiota habitat regulation and cell signaling. BA-activated nuclear receptors regulate the enterohepatic circulation of BAs which play a role in energy, lipid, glucose, and drug metabolism. The gut microbiota plays an essential role in the biotransformation of BAs and regulates BAs composition and metabolism. Therefore, altered gut microbial and BAs activity can affect human metabolism and thus result in the alteration of metabolic pathways and the occurrence of metabolic diseases/syndromes, such as diabetes mellitus, obesity/hypercholesterolemia, and cardiovascular diseases. BAs and their metabolites are used to treat altered gut microbiota and metabolic diseases. This review explores the increasing body of evidence that links alterations of gut microbial activity and BAs with the pathogenesis of metabolic diseases. Moreover, we summarize existing research on gut microbes and BAs in relation to intracellular pathways pertinent to metabolic disorders. Finally, we discuss how therapeutic interventions using BAs can facilitate microbiome functioning and ease metabolic diseases.
Currently, obesity is one of the biggest health burdens facing society because it causes several comorbidities, such as type 2 diabetes, atherosclerosis, and heart disease. Obesity is also linked to multiple types of cancer. Obesity is the second most common preventable cause of cancer after smoking; the rates of obesity are increasing worldwide, as are the rates of obesity-associated cancer. Multiple factors link obesity to cancer, such as increased levels of growth hormones and adipokines, gut dysbiosis, altered tumor metabolism, and chronic low-grade inflammation. More recently, obesity has been shown to also affect the immune response against cancer. In this review we discuss the interplay between obesity, the immune system, and cancer.
The extension of biological inheritance beyond gene-centrism is at the center of many debates in evolutionary biology, but it has been relatively ignored in the field of biomedicine. The purpose of this prospective paper is to highlight the potential impact of a new vision of inheritance on medical theory, notably on the concept of hereditary disease. It is also to underline some related practical and social issues.
Obesity is associated with an imbalance of micro-and macro-nutrients, dysbiosis, and a “leaky” gut phenomenon. Polyphenols, such as curcumin, resveratrol, and anthocyanin may alleviate the systemic effects of obesity, potentially by improving gut microbiota, intestinal barrier integrity (IBI), and zinc homeostasis. The essential micronutrient zinc plays a crucial role in the regulation of enzymatic processes, including inflammation, maintenance of the microbial ecology, and intestinal barrier integrity. In this review, we focus on IBI– which prevents intestinal lipopolysaccharide (LPS) leakage – as a critical player in polyphenol-mediated protective effects against obesity-associated white adipose tissue (WAT) inflammation. This occurs through mechanisms that block the movement of the bacterial endotoxin LPS across the gut barrier. Available research suggests that polyphenols reduce WAT and systemic inflammation via crosstalk with inflammatory NF-κB, the mammalian target of rapamycin (mTOR) signaling and zinc homeostasis.
The Human Microbial Metabolome Database (MiMeDB) (https://mimedb.org) is a comprehensive, multi-omic, microbiome resource that connects: (i) microbes to microbial genomes; (ii) microbial genomes to microbial metabolites; (iii) microbial metabolites to the human exposome and (iv) all of these ‘omes’ to human health. MiMeDB was established to consolidate the growing body of data connecting the human microbiome and the chemicals it produces to both health and disease. MiMeDB contains detailed taxonomic, microbiological and body-site location data on most known human microbes (bacteria and fungi). This microbial data is linked to extensive genomic and proteomic sequence data that is closely coupled to colourful interactive chromosomal maps. The database also houses detailed information about all the known metabolites generated by these microbes, their structural, chemical and spectral properties, the reactions and enzymes responsible for these metabolites and the primary exposome sources (food, drug, cosmetic, pollutant, etc.) that ultimately lead to the observed microbial metabolites in humans. Additional, extensively referenced data about the known or presumptive health effects, measured biosample concentrations and human protein targets for these compounds is provided. All of this information is housed in richly annotated, highly interactive, visually pleasing database that has been designed to be easy to search, easy to browse and easy to navigate. Currently MiMeDB contains data on 626 health effects or bioactivities, 1904 microbes, 3112 references, 22 054 reactions, 24 254 metabolites or exposure chemicals, 648 861 MS and NMR spectra, 6.4 million genes and 7.6 billion DNA bases. We believe that MiMeDB represents the kind of integrated, multi-omic or systems biology database that is needed to enable comprehensive multi-omic integration.
Precision Nutrition is an emerging area of nutrition research that focuses on understanding metabolic variability within and between individuals, and helps develop customized dietary plans and interventions to maintain optimum individual health. It encompasses nutritional genomics (gene-nutrient interactions), epigenetics, microbiome, and environmental factors. Obesity is a complex disease that is affected by genetic and environmental factors, and thus a relevant target of precision nutrition-based approaches. Recent studies have shown significant associations between obesity phenotypes (body weight, BMI, waist circumference, central and regional adiposity) and genetic variants, epigenetic factors (DNA methylation and non-coding RNA), microbial species and environment (socio-demographics and physical activity). Additionally, studies have also shown that the interactions between the genetic variants, microbial metabolites, and epigenetic factors affect energy balance and adiposity These include variants in FTO, MC4R, PPARs, APOAs, FADSs genes, DNA methylation in CpG island regions and specific miRNAs and microbial species such as Firmicutes, Bacteriodes, Clostridiales, etc. Similarly, studies have shown that microbial metabolites, folate and B-vitamins and short-chain fatty acids interact with miRNAs to influence obesity phenotypes. With the advent of next generation sequencing and analytical approaches, the advances in precision nutrition have the potential to lead to new paradigms, which can further lead to interventions or customized treatments specific to individuals or susceptible group of individuals. This review highlights the recent advances in precision nutrition as applied to obesity and projects the importance of precision nutrition in obesity and weight management.
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.
Excessive lipid accumulation in white adipose tissue (WAT) is the major cause of obesity. Herein, we investigated the anti-obesity effect and molecular mechanism of a botanical mixture of 30% EtOH extract from the leaves of Inula japonica and Potentilla chinensis (EEIP) in 3T3-L1 preadipocytes and high-fat diet (HFD)-fed obese mice. In vitro, EEIP prevented lipid accumulation by downregulating the expression of lipogenesis-related transcription factors such as CCAAT/enhancer binding protein (C/EBP)α, peroxisome proliferator-activated receptor (PPAR)γ, and sterol regulatory element binding protein (SREBP)-1 via AMP-activated protein kinase (AMPK) activation and G0/G1 cell cycle arrest by regulating the Akt-mTOR pathways without inducing cytotoxicity. In vivo, EEIP significantly reduced body weight gain and body fat mass in the group administered concurrently with HFD (pre-) or administered during the maintenance of HFD (post-) including subcutaneous, gonadal, renal, and mesenteric fats, and improved blood lipid profiles and metabolic hormones. EEIP pre-administration also alleviated WAT hypertrophy and liver lipid accumulation by reducing C/EBPα, PPARγ, and SREBP-1 expression via AMPK activation. In the brown adipose tissue, EEIP pre-administration upregulated the expression of thermogenic factors. Furthermore, EEIP improved the HFD-induced altered gut microbiota in mice. Taken together, our data indicated that EEIP improves HFD-induced obesity through adipogenesis inhibition in the WAT and liver and is a promising dietary natural material for improving obesity.
Nutritional exposure and, therefore, the metabolic environment during early human development can affect health later in life. This can go beyond the nutrients consumed; there is evidence that the development and modulation of the gut microbiome during early life can affect human growth, development, and health, and the gut microbiome is associated with the risk of obesity later in life. The primary aim of this review was to evaluate existing evidence, to identify the components of human breast milk, which may modulate the gut microbiome, and to assess the impact of the gut microbiome on the risk of becoming obese later in life. This review also considers maternal and child characteristics, and confounders of breastfeeding and how they impact on the infant gut microbiome. Current evidence supports a positive association between fecal, branched short-chain fatty acids and human milk oligosaccharide diversity and a gut microbiome associated with better metabolic health. A negative correlation was found between microbiome diversity and human milk oligosaccharide evenness, which was associated with a greater fat mass and percentage of fat. The components of human breast milk, including oligosaccharides, probiotics, milk fat globule membrane, and adiponectin, were hypothesized to positively influence infant growth and body weight by modulating the microbial diversity and composition of the gut. Maternal diet, timing and duration of breast feeding, and the mode of delivery were all shown to affect the human milk microbiota. However, more experimental studies with long follow-up are required to shed light on the governing mechanisms linking breast milk components with a diverse infant microbiome and healthier body weight later in life.
Malnutrition is a global health issue and the leading cause of childhood morbidity and mortality under 5 years old. Malnutrition comprises undernutrition (stunting, wasting, underweight), overweight, and obesity. Infancy and child malnutrition are substantially influenced by a number of variables, such as insufficient nutrients, early birth, intestinal inflammation, and gastrointestinal tract microbiota. A variety of environmental factors have been identified that modulate the structure and diversity of newborns' gut microbiomes and their long-term health. Significant data demonstrate that the functional potency and compositional diversity of the microbiome differ in different types of malnutrition. The divergence in the gut microbiome composition between malnourished and healthy children can be observed at an age as young as 12 months. This focuses on variations in the gut microbiome that may influence adult obesity/health status, beginning in the early years of life. The therapeutic potential of supporting a healthy microbiome in malnourished children is being studied as a technique to aid in the fight against malnutrition. The goal of this chapter was to determine the makeup of gut microbiota in obese and undernourished children under the age of 5 years.
Obesity is a global epidemic. The rates of obesity in infants and children continue increasing, particularly in the more underserved sectors and most populous areas of the world. Nutrition in early life is a major determinant of childhood and adult obesity risk and sets the course for an individual’s future metabolic health. Therefore, prevention is critical, and needs to start early, during gestation and the first 2 years after birth, a child’s first 1000 days of life. Early life offers a unique opportunity for a child’s parents and caregivers to provide such nutrition and to shape the food preferences and dietary habits that may last a lifetime.
The paper discusses factors associated with overweight and obesity in childhood and later life, with a focus on those which can be variably modified in an infant’s immediate environment, primarily via a child’s caregivers. These include maternal weight and weight gain in pregnancy, mode of birth, perinatal and postnatal use of antibiotics, feeding of infant formula vs breastfeeding, feeding with a bottle, time of introduction of complementary foods and beverages, macronutrient composition of the infant diet (particularly excess protein, energy, and sugars), short sleep, excess of screen time and sedentary behaviors, and the lack of parental responsive feeding behaviors. Finally, we review some aspects of interventional approaches that can be taken. Obesity prevention will require continued social and environmental changes to support the goal of providing adequate nutrition and a level of energy intake in balance with each individual’s needs and requirements.
Obesity is characterized by abnormal or excessive accumulation of fats, resulting from a long-term imbalance between energy consumption and its expenditure. It is not only a primary cosmetic concern but also a grave medical issue that increases the propensity toward several other illnesses, such as cardiovascular diseases, diabetes, high blood pressure, certain cancers, and hormonal imbalances. Increasing concern over potential health risks associated with this condition has now become universal, owing to the exponential increase in obese and overweight individuals globally, during the past four decades. Prevention and treatment of obesity and its associated risks have proven to be complicated, thereby posing hindrance and limiting the number of practical approaches that can tackle this problem. This indicates that there is a dire need for novel therapeutic modalities to address this issue. Over the past few years, mechanistic studies have indicated that gastrointestinal microbiota can influence obesity as well as obesity-related disorders. Recent comparative analyses between the gut microbiome of lean and obese individuals have revealed a potential link between obesity and variations in the gut flora. This fact raises the possibility that manipulation of the gut microflora could facilitate weight loss and/or aid in combating weight gain in humans. Thus, this chapter focuses on understanding the intrinsic link between gut microbiome and obesity, along with its therapeutic significance in managing or preventing obesity and maintaining overall health.
Obesity is associated with alteration of the gut microbiota. In order to clarify the effect of Lactobacillus-containing probiotics (LCP) on weight we performed a meta-analysis of clinical studies and experimental models. We intended to assess effects by Lactobacillus species.
A broad search with no date or language restriction was performed. We included randomized controlled trials (RCTs) and comparative clinical studies in humans and animals or experimental models assessing the effect of Lactobacillus-containing probiotics on weight. We primarily attempted to extract and use change from baseline values. Data were extracted independently by two authors. Results were pooled by host and by Lactobacillus species and are summarized in a meta-analysis of standardized difference in means (SMDs).
We identified and included 17 RCTs in humans, 51 studies on farm animals and 14 experimental models. Lactobacillus acidophilus administration resulted in significant weight gain in humans and in animals (SMD 0.15; 95% confidence intervals 0.05-0.25). Results were consistent in humans and animals. Lactobacillus fermentum and Lactobacillus ingluviei were associated with weight gain in animals. Lactobacillus plantarum was associated with weight loss in animals and Lactobacillus gasseri was associated with weight loss both in obese humans and in animals.
Different Lactobacillus species are associated different effects on weight change that are host-specific. Further studies are needed to clarify the role of Lactobacillus species in the human energy harvest and weight regulation. Attention should be drawn to the potential effects of commonly marketed lactobacillus-containing probiotics on weight gain.
The impact of antibiotics on the human gut microbiota is a significant concern. Antibiotic-associated diarrhea has been on the rise for the past few decades with the increasing usage of antibiotics. Clostridium difficile infections (CDI) have become one of the most prominent types of infectious diarrheal disease, with dramatically increased incidence in both the hospital and community setting worldwide. Studies show that variability in the innate host response may in part impact upon CDI severity in patients. That being said, CDI is a disease that shows the most prominent links to alterations to the gut microbiota, in both cause and treatment. With recurrence rates still relatively high, it is important to explore alternative therapies to CDI. Fecal microbiota transplantation (FMT) and other types of bacteriotherapy have become exciting avenues of treatment for CDI. Recent clinical trials have generated excitement for the use of FMT as a therapeutic option for CDI; however, the exact components of the human gut microbiota needed for protection against CDI have remained elusive. Additional investigations on the effects of antibiotics on the human gut microbiota and subsequent CDI will help reduce the socioeconomic burden of CDI and potentially lead to new therapeutic modalities.
Obesity has become a major health problem in developed countries and is rapidly catching up in the developing world due to changes in their life style. Dietary incorporation of functional foods, including probiotic fermented milk and herbal ingredients, is being tried to ameliorate metabolic disorders. In the present study, the effect of dietary supplementation of a probiotic (Lactobacillus rhamnosus NCDC 17) fermented milk alone or either of the herbal preparations (Aloe vera/Gymnema sylvestre powders, 1% w/w) on the progression of obesity has been studied in C57BL/6J mice fed with a high fat diet for 12 weeks. At the end of the experimental period, oral administration of L. rhamnosus and herbs resulted in a significant decrease in the body weight, epididymal fat mass, fasting blood glucose and serum insulin levels. Supplementation of the probiotic L. rhamnosus alone and in combination with herbs showed a significant decrease in the adipocyte cell size and an increase in the number. Finally, obesity related adipokines levels were maintained at normal by the treatment groups. Thus, dietary intervention of milk fermented with probiotic L. rhamnosus alone or in combination with any of the herbal preparations seems to show anti-obesity and anti-inflammatory properties.
ᅟ
The advancement of DNA/RNA, proteins, and metabolite analytical platforms, combined with increased computing technologies, has transformed the field of microbial community analysis. This transformation is evident by the exponential increase in the number of publications describing the composition and structure, and sometimes function, of the microbial communities inhabiting the human body. This rapid evolution of the field has been accompanied by confusion in the vocabulary used to describe different aspects of these communities and their environments. The misuse of terms such as microbiome, microbiota, metabolomic, and metagenome and metagenomics among others has contributed to misunderstanding of many study results by the scientific community and the general public alike. A few review articles have previously defined those terms, but mainly as sidebars, and no clear definitions or use cases have been published. In this editorial, we aim to propose clear definitions of each of these terms, which we would implore scientists in the field to adopt and perfect.
Gnotobiotic (GN) rodent models have provided insight into the contributions of the gut microbiota to host health and preventing disease. However, rodent models are limited by several important physiological and metabolic differences from humans, and many rodent models do not dependably replicate the clinical manifestations of human diseases. Due to the high degree of similarity in anatomy, physiology, immunology and brain growth, the domestic pig (Sus scrofa) is considered a clinically relevant model to study factors influencing human gastrointestinal, immune, and brain development. Gnotobiotic piglet models have been developed and shown to recapitulate key aspects of GN rodent models. Human microbiota-associated (HMA) piglets have been established using inocula from infants, children, and adults. The gut microbiota of recipient HMA piglets was more similar to that of the human donor than that of conventionally reared piglets harboring a pig microbiota. Moreover, Bifidobacterium and Bacteroides, two predominant bacterial groups of infant gut, were successfully established in the HMA piglets. Thus, the HMA pig model has the potential to be a valuable model for investigating how the gut microbiota composition changes in response to environmental factors, such as age, diet, vaccination, antibiotic use and infection. The HMA also represents a robust model for screening the efficacy of pre- and probiotic interventions. Lastly, HMA piglets can be an ideal model with which to elucidate microbe-host interactions in human health and disease due to the similarities to humans in anatomy, physiology, developmental maturity at birth, and the pathophysiology of many human diseases.
© The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Fecal microbiota transplantation (FMT) is a promising treatment for recurrent Clostridium difficile infection. We report a case of a woman successfully treated with FMT who developed new-onset obesity after receiving stool
from a healthy but overweight donor. This case may stimulate further studies on the mechanisms of the nutritional-neural-microbiota
axis and reports of outcomes in patients who have used nonideal donors for FMT.
Mammals exhibit marked interindividual variations in their gut microbiota, but it remains unclear if this is primarily driven by host genetics or by extrinsic factors like dietary intake. To address this, we examined the effect of dietary perturbations on the gut microbiota of five inbred mouse strains, mice deficient for genes relevant to host-microbial interactions (MyD88(-/-), NOD2(-/-), ob/ob, and Rag1(-/-)), and >200 outbred mice. In each experiment, consumption of a high-fat, high-sugar diet reproducibly altered the gut microbiota despite differences in host genotype. The gut microbiota exhibited a linear dose response to dietary perturbations, taking an average of 3.5 days for each diet-responsive bacterial group to reach a new steady state. Repeated dietary shifts demonstrated that most changes to the gut microbiota are reversible, while also uncovering bacteria whose abundance depends on prior consumption. These results emphasize the dominant role that diet plays in shaping interindividual variations in host-associated microbial communities.
Copyright © 2015 Elsevier Inc. All rights reserved.
The intestinal microbiota can influence host metabolism. When given early in life, agents that disrupt microbiota composition, and consequently the metabolic activity of the microbiota, can affect the body mass of the host by either promoting weight gain or stunting growth. These effects are consistent with the role of the microbiota during development. In this Perspective, we posit that microbiota disruptions in early life can have long-lasting effects on body weight in adulthood. Furthermore, we examine the dichotomy between antibiotic-induced repression and promotion of growth and review the experimental and epidemiological evidence that supports these phenotypes. Considering the characteristics of the gut microbiota in early life as a distinct dimension of human growth and development, as well as comprehending the susceptibility of the microbiota to perturbation, will allow for increased understanding of human physiology and could lead to development of interventions to stem current epidemic diseases such as obesity, type 1 diabetes mellitus and type 2 diabetes mellitus.
Background & Aims: Several studies have reported the effects of prebiotics and synbiotics supplementation in lipid profile and glucose homeostasis, however a pooled analysis of clinical trials that assessed these parameters has not been performed in overweight or obese individuals. The aim of this study was to evaluate the effects of prebiotics and synbiotics on plasma lipid profile, fasting insulin and fasting glucose in adults with overweight or obesity.
Methods: Randomized controlled trials were systematically searched before May 2014 in electronic databases and screening reference lists. Combined and stratified (diabetics and non-diabetics trials) meta-analyzes were performed.
Results: Thirteen trials, representing 513 adult participants with Body Mass Index ≥ 25 kg/m² were included. Prebiotic supplementation reduced plasma total cholesterol (SMD -0.25; 95% CI -0.48, -0.02) and LDL-c (SMD -0.22; 95% CI -0.44, -0.00) concentrations in overall analysis, and reduced triglycerides (SMD -0.72; 95% CI -1.20, -0.23) and increased HDL-c (SMD 0.49; 95% CI 0.01, 0.97) concentrations in diabetic trials. Synbiotic supplementation reduced plasma fasting insulin (SMD -0.39; 95% CI -0.75, -0.02) and triglycerides (SMD -0.43; 95% CI -0.70, -0.15) concentrations.
Conclusions: The improvement of the evaluated parameters supports prebiotics and synbiotics supplementation as an adjuvant therapy in obesity-related comorbidities, such as dyslipidemia and insulin resistance.
Unlabelled:
Growing evidence shows that gut microbes are key factors involved in the regulation of energy homeostasis, metabolic inflammation, lipid metabolism, and glucose metabolism. Therefore, gut microbiota modulations caused by selectively fermented oligosaccharides or probiotic bacteria constitute an interesting target in the physiopathology of obesity. However, to date, no probiotic yeast has been investigated in this context. Therefore, our study aimed to evaluate the impact of the most-studied probiotic yeast (i.e., Saccharomyces boulardii Biocodex) on obesity and associated metabolic features, such as fat mass development, hepatic steatosis, and low-grade inflammation, in obese mice. S. boulardii was administered daily by oral gavage to leptin-resistant obese and type 2 diabetic mice (db/db) for 4 weeks. We found that S. boulardii-treated mice exhibited reduced body weight, fat mass, hepatic steatosis, and inflammatory tone. Interestingly, these effects of S. boulardii on host metabolism were associated with local effects in the intestine. S. boulardii increased cecum weight and cecum tissue weight but also induced dramatic changes in the gut microbial composition at the phylum, family, and genus levels. These gut microbiota changes in response to S. boulardii may also be correlated with the host metabolism response. In conclusion, this study demonstrates for the first time that S. boulardii may act as a beneficial probiotic treatment in the context of obesity and type 2 diabetes.
Importance:
To date, no probiotic yeast have been investigated in the context of obesity and type 2 diabetes. Here we found that type 2 diabetic and obese mice (db/db) treated with Saccharomyces boulardii exhibited reduced body weight, fat mass, hepatic steatosis, and inflammatory tone. These effects on host metabolism were associated with local effects in the intestine. Importantly, by using pyrosequencing, we found that S. boulardii treatment induces changes of the gut microbiota composition at the phylum, family, and genus levels. Moreover, we found that gut microbiota changes in response to S. boulardii were correlated with several host metabolism responses.
We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.
The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult
female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different
levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as
well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding
fecal bacterial culture collections. Cohousing mice harboring an obese twin’s microbiota (Ob) with mice containing the lean
co-twin’s microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in
Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota
and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.
Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity, and improved glucose metabolism. These effects are not simply attributable to decreased caloric intake or absorption, but the mechanisms linking rearrangement of the gastrointestinal tract to these metabolic outcomes are largely unknown. Studies in humans and rats have shown that RYGB restructures the gut microbiota, prompting the hypothesis that some of the effects of RYGB are caused by altered host-microbial interactions. To test this hypothesis, we used a mouse model of RYGB that recapitulates many of the metabolic outcomes in humans. 16S ribosomal RNA gene sequencing of murine fecal samples collected after RYGB surgery, sham surgery, or sham surgery coupled to caloric restriction revealed that alterations to the gut microbiota after RYGB are conserved among humans, rats, and mice, resulting in a rapid and sustained increase in the relative abundance of Gammaproteobacteria (Escherichia) and Verrucomicrobia (Akkermansia). These changes were independent of weight change and caloric restriction, were detectable throughout the length of the gastrointestinal tract, and were most evident in the distal gut, downstream of the surgical manipulation site. Transfer of the gut microbiota from RYGB-treated mice to nonoperated, germ-free mice resulted in weight loss and decreased fat mass in the recipient animals relative to recipients of microbiota induced by sham surgery, potentially due to altered microbial production of short-chain fatty acids. These findings provide the first empirical support for the claim that changes in the gut microbiota contribute to reduced host weight and adiposity after RYGB surgery.
Objective:
To determine the effects of naturally derived probiotic strains individually or combination on a short-term diet-induced obesity model.
Design and methods:
C57BL/6J mice (n = 50) were randomly divided into five groups, then fed a high-fat high-cholesterol diet (HFCD), HFCD and Lactobacillus plantarum KY1032 (PL, 10(10) cfu/day), HFCD and Lactobacillus curvatus HY7601 (CU, 10(10) cfu/day), HFCD and in combination with PL+CU (10(10) cfu/day), or a normal diet (ND) for 9 weeks.
Results:
PL and CU showed distinct and shared metabolic activity against a panel of 50 carbohydrates. Fat accumulation in adipose tissue and liver was significantly reduced by probiotic strains CU or PL+CU. Probiotic strains CU or PL+CU reduced cholesterol in plasma and liver, while PL+CL had a synergistic effect on hepatic triglycerides. Probiotic strains PL+CU combination was more effective for inhibiting gene expressions of various fatty acid synthesis enzymes in the liver, concomitant with decreases in fatty acid oxidation-related enzyme activities and their gene expressions.
Conclusions:
Multi-strain probiotics may prove more beneficial than single-strain probiotics to combat fat accumulation and metabolic alterations in diet-induced obesity.
The gut microbiota is a complex ecosystem that has a symbiotic relationship with its host. An association between the gut microbiota and disease was first postulated in the early 20(th) century. However, until the 1990s, knowledge of the gut microbiota was limited because bacteriological culture was the only technique available to characterize its composition. Only a fraction (estimated at <30%) of the gut microbiota has been cultured to date. Since the 1990s, advances in culture-independent techniques have spearheaded our knowledge of the complexity of this ecosystem. These techniques have elucidated the microbial diversity of the gut microbiota and have shown that alterations in the gut microbiota composition and function are associated with certain disease states, such as IBD and obesity. These new techniques are fast, facilitate high throughput, identify organisms that are uncultured to date and enable enumeration of organisms present in the gut microbiota. This Review discusses the techniques that can used to characterize the gut microbiota, when they can be applied to human studies and their relative advantages and limitations.
Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.
Studies in mice indicate that the gut microbiome influences both sides of the energy-balance equation by contributing to nutrient absorption and regulating host genes that affect adiposity. However, it remains uncertain as to what extent gut microbiota are an important regulator of nutrient absorption in humans.
With the use of a carefully monitored inpatient study cohort, we tested how gut bacterial community structure is affected by altering the nutrient load in lean and obese individuals and whether their microbiota are correlated with the efficiency of dietary energy harvest.
We investigated dynamic changes of gut microbiota during diets that varied in caloric content (2400 compared with 3400 kcal/d) by pyrosequencing bacterial 16S ribosomal RNA (rRNA) genes present in the feces of 12 lean and 9 obese individuals and by measuring ingested and stool calories with the use of bomb calorimetry.
The alteration of the nutrient load induced rapid changes in the gut microbiota. These changes were directly correlated with stool energy loss in lean individuals such that a 20% increase in Firmicutes and a corresponding decrease in Bacteroidetes were associated with an increased energy harvest of ≈150 kcal. A high degree of overfeeding in lean individuals was accompanied by a greater fractional decrease in stool energy loss.
These results show that the nutrient load is a key variable that can influence the gut (fecal) bacterial community structure over short time scales. Furthermore, the observed associations between gut microbes and nutrient absorption indicate a possible role of the human gut microbiota in the regulation of the nutrient harvest. This trial was registered at clinicaltrials.gov as NCT00414063.
Gut microbial composition depends on different dietary habits just as health depends on microbial metabolism, but the association of microbiota with different diets in human populations has not yet been shown. In this work, we compared the fecal microbiota of European children (EU) and that of children from a rural African village of Burkina Faso (BF), where the diet, high in fiber content, is similar to that of early human settlements at the time of the birth of agriculture. By using high-throughput 16S rDNA sequencing and biochemical analyses, we found significant differences in gut microbiota between the two groups. BF children showed a significant enrichment in Bacteroidetes and depletion in Firmicutes (P < 0.001), with a unique abundance of bacteria from the genus Prevotella and Xylanibacter, known to contain a set of bacterial genes for cellulose and xylan hydrolysis, completely lacking in the EU children. In addition, we found significantly more short-chain fatty acids (P < 0.001) in BF than in EU children. Also, Enterobacteriaceae (Shigella and Escherichia) were significantly underrepresented in BF than in EU children (P < 0.05). We hypothesize that gut microbiota coevolved with the polysaccharide-rich diet of BF individuals, allowing them to maximize energy intake from fibers while also protecting them from inflammations and noninfectious colonic diseases. This study investigates and compares human intestinal microbiota from children characterized by a modern western diet and a rural diet, indicating the importance of preserving this treasure of microbial diversity from ancient rural communities worldwide.
Diet and nutritional status are among the most important modifiable determinants of human health. The nutritional value of food is influenced in part by a person's gut microbial community (microbiota) and its component genes (microbiome). Unraveling the interrelations among diet, the structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by variations in human environmental exposures, microbial ecology, and genotype. To help overcome these problems, we created a well-defined, representative animal model of the human gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into germ-free C57BL/6J mice. Culture-independent metagenomic analysis of the temporal, spatial, and intergenerational patterns of bacterial colonization showed that these humanized mice were stably and heritably colonized and reproduced much of the bacterial diversity of the donor's microbiota. Switching from a low-fat, plant polysaccharide-rich diet to a high-fat, high-sugar "Western" diet shifted the structure of the microbiota within a single day, changed the representation of metabolic pathways in the microbiome, and altered microbiome gene expression. Reciprocal transplants involving various combinations of donor and recipient diets revealed that colonization history influences the initial structure of the microbial community but that these effects can be rapidly altered by diet. Humanized mice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobiotic mice will be useful for conducting proof-of-principle "clinical trials" that test the effects of environmental and genetic factors on the gut microbiota and host physiology. Nearly full-length 16S rRNA gene sequences are deposited in GenBank under the accession numbers GQ491120 to GQ493997.
To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.
We have previously shown that gut microbial fermentation of prebiotics promotes satiety and lowers hunger and energy intake in humans. In rodents, these effects are associated with an increase in plasma gut peptide concentrations, which are involved in appetite regulation and glucose homeostasis.
Our aim was to examine the effects of prebiotic supplementation on satiety and related hormones during a test meal for human volunteers by using a noninvasive micromethod for blood sampling to measure plasma gut peptide concentrations.
This study was a randomized, double-blind, parallel, placebo-controlled trial. A total of 10 healthy adults (5 men and 5 women) were randomly assigned to groups that received either 16 g prebiotics/d or 16 g dextrin maltose/d for 2 wk. Meal tolerance tests were performed in the morning to measure the following: hydrogen breath test, satiety, glucose homeostasis, and related hormone response.
We show that the prebiotic treatment increased breath-hydrogen excretion (a marker of gut microbiota fermentation) by approximately 3-fold and lowered hunger rates. Prebiotics increased plasma glucagon-like peptide 1 and peptide YY concentrations, whereas postprandial plasma glucose responses decreased after the standardized meal. The areas under the curve for plasma glucagon-like peptide 1 and breath-hydrogen excretion measured after the meal (0-60 min) were significantly correlated (r = 0.85, P = 0.007). The glucose response was inversely correlated with the breath-hydrogen excretion areas under the curve (0-180 min; r = -0.73, P = 0.02).
Prebiotic supplementation was associated with an increase in plasma gut peptide concentrations (glucagon-like peptide 1 and peptide YY), which may contribute in part to changes in appetite sensation and glucose excursion responses after a meal in healthy subjects.
Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the Bacteria in the human intestinal community were highly diverse, they fell mainly into 6 bacterial divisions that had distinct differences in the 3 study groups. Specifically, Firmicutes were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of Gammaproteobacteria. Numbers of the H(2)-producing Prevotellaceae were highly enriched in the obese individuals. Unlike the highly diverse Bacteria, the Archaea comprised mainly members of the order Methanobacteriales, which are H(2)-oxidizing methanogens. Using real-time PCR, we detected significantly higher numbers of H(2)-utilizing methanogenic Archaea in obese individuals than in normal-weight or post-gastric-bypass individuals. The coexistence of H(2)-producing bacteria with relatively high numbers of H(2)-utilizing methanogenic Archaea in the gastrointestinal tract of obese individuals leads to the hypothesis that interspecies H(2) transfer between bacterial and archaeal species is an important mechanism for increasing energy uptake by the human large intestine in obese persons. The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion.
It has been proposed that the development of obesity in humans is influenced by the relative proportions of the two major phyla of bacteria (Bacteroidetes and Firmicutes) present in the large intestine.
To examine the relationships between body mass index, weight loss and the major bacterial groups detected in fecal samples.
Major groups of fecal bacteria were monitored using fluorescent in situ hybridization (FISH) in obese and non-obese subjects under conditions of weight maintenance, and in obese male volunteers undergoing weight loss on two different reduced carbohydrate weight-loss diets given successively for 4 weeks each.
We detected no difference between obese and non-obese individuals in the proportion of Bacteroidetes measured in fecal samples, and no significant change in the percentage of Bacteroidetes in feces from obese subjects on weight loss diets. Significant diet-dependent reductions in a group of butyrate-producing Firmicutes were, however, detected in fecal samples from obese subjects on weight loss diets.
Diets designed to achieve weight loss in obese subjects can significantly alter the species composition of the gut microbiota, but we find no evidence that the proportions of Bacteroidetes and Firmicutes among fecal bacteria have a function in human obesity.
The human gastrointestinal (GI) tract harbors a complex community of bacterial cells in the mucosa, lumen, and feces. Since
most attention has been focused on bacteria present in feces, knowledge about the mucosa-associated bacterial communities
in different parts of the colon is limited. In this study, the bacterial communities in feces and biopsy samples from the
ascending, transverse, and descending colons of 10 individuals were analyzed by using a 16S rRNA approach. Flow cytometric
analysis indicated that 105 to 106 bacteria were present in the biopsy samples. To visualize the diversity of the predominant and the Lactobacillus group community, denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene amplicons was performed. DGGE analysis
and similarity index comparisons demonstrated that the predominant mucosa-associated bacterial community was host specific
and uniformly distributed along the colon but significantly different from the fecal community (P < 0.01). The Lactobacillus group-specific profiles were less complex than the profiles reflecting the predominant community. For 6 of the 10 individuals
the community of Lactobacillus-like bacteria in the biopsy samples was similar to that in the feces. Amplicons having 99% sequence similarity to the 16S
ribosomal DNA of Lactobacillus gasseri were detected in the biopsy samples of nine individuals. No significant differences were observed between healthy and diseased
individuals. The observed host-specific DGGE profiles of the mucosa-associated bacterial community in the colon support the
hypothesis that host-related factors are involved in the determination of the GI tract microbial community.
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
In the present paper, we summarise the data supporting the following hypothesis: dietary inulin-type fructans extracted from chicory root may modulate the production of peptides, such as incretins, by endocrine cells present in the intestinal mucosa, this phenomenon being involved in the regulation of food intake and/or systemic effects. To test this hypothesis, male Wistar rats received for 3 weeks either a standard diet or the same diet supplemented with 10 % inulin-type fructans with different degrees of polymerisation. All the effects were most pronounced with the diet containing oligofructose, and consisted of (i) a decrease in mean daily energy intake and in epididymal fat mass; (ii) a higher caecal pool of the anorexigenic glucagon-like peptide-1 (7-36) amide (GLP-1), and peptide YY (PYY), due to caecal tissue proliferation; (iii) an increase in GLP-1 and of its precursor - proglucagon mRNA - concentrations in the proximal colon; (iv) an increase in portal serum level of GLP-1 and PYY; (v) a decrease in serum orexigenic peptide ghrelin. Moreover, oligofructose supplementation improved glucose homeostasis (i.e. decreased glycaemia, increased pancreatic and serum insulin content) in diabetic rats previously treated with streptozotocin, a phenomenon that is partly linked to the reduction in food intake and that correlates with the increase in colic and portal GLP-1 content. Based on these results it appears justified to test, in human subjects, the hypothesis that dietary inulin-type fructans could play a role in the management of obesity and diabetes through their capacity to promote secretion of endogenous gastrointestinal peptides involved in appetite regulation.
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
Due to its low digestibility in the small intestine, a major fraction of the polyol isomalt reaches the colon. However, little is known about effects on the intestinal microflora. During two 4-week periods in a double-blind, placebo-controlled, cross-over design, nineteen healthy volunteers consumed a controlled basal diet enriched with either 30 g isomalt or 30 g sucrose daily. Stools were collected at the end of each test phase and various microbiological and luminal markers were analysed. Fermentation characteristics of isomalt were also investigated in vitro. Microbiological analyses of faecal samples indicated a shift of the gut flora towards an increase of bifidobacteria following consumption of the isomalt diet compared with the sucrose diet (P<0.05). During the isomalt phase, the activity of bacterial beta-glucosidase decreased (P<0.05) whereas beta-glucuronidase, sulfatase, nitroreductase and urease remained unchanged. Faecal polyamines were not different between test periods with the exception of cadaverine, which showed a trend towards a lower concentration following isomalt (P=0.055). Faecal SCFA, lactate, bile acids, neutral sterols, N, NH3, phenol and p-cresol were not affected by isomalt consumption. In vitro, isomalt was metabolized in several bifidobacteria strains and yielded high butyrate concentrations. Isomalt, which is used widely as a low-glycaemic and low-energy sweetener, has to be considered a prebiotic carbohydrate that might contribute to a healthy luminal environment of the colonic mucosa.
Probiotics are marketed in several countries and widely used by pediatric health care providers. Although probiotics can be helpful for specific disorders, they have been broadly prescribed for disorders without clear evidence to support their use. Furthermore, in certain specific conditions, probiotics cause clinical deterioration. This report is a review and evaluation of the evidence or lack thereof to support a beneficial effect of probiotic agents in a variety of pediatric conditions and to review the safety and potential adverse events that may be encountered when using probiotics. It is also important to emphasize that probiotics are highly heterogeneous with differences in composition, biological activity, and dose among the different probiotic preparations.
The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
Animal studies suggest that prebiotics and probiotics exert protective effects against tumor development in the colon, but human data supporting this suggestion are weak.
The objective was to verify whether the prebiotic concept (selective interaction with colonic flora of nondigested carbohydrates) as induced by a synbiotic preparation-oligofructose-enriched inulin (SYN1) + Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (BB12)-is able to reduce the risk of colon cancer in humans.
The 12-wk randomized, double-blind, placebo-controlled trial of a synbiotic food composed of the prebiotic SYN1 and probiotics LGG and BB12 was conducted in 37 colon cancer patients and 43 polypectomized patients. Fecal and blood samples were obtained before, during, and after the intervention, and colorectal biopsy samples were obtained before and after the intervention. The effect of synbiotic consumption on a battery of intermediate bio-markers for colon cancer was examined.
Synbiotic intervention resulted in significant changes in fecal flora: Bifidobacterium and Lactobacillus increased and Clostridium perfringens decreased. The intervention significantly reduced colorectal proliferation and the capacity of fecal water to induce necrosis in colonic cells and improve epithelial barrier function in polypectomized patients. Genotoxicity assays of colonic biopsy samples indicated a decreased exposure to genotoxins in polypectomized patients at the end of the intervention period. Synbiotic consumption prevented an increased secretion of interleukin 2 by peripheral blood mononuclear cells in the polypectomized patients and increased the production of interferon gamma in the cancer patients.
Several colorectal cancer biomarkers can be altered favorably by synbiotic intervention.
