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Gut microbiota and energy balance: Role in obesity

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Abstract

The microbial community populating the human digestive tract has been linked to the development of obesity, diabetes and liver diseases. Proposed mechanisms on how the gut microbiota could contribute to obesity and metabolic diseases include: (1) improved energy extraction from diet by the conversion of dietary fibre to SCFA; (2) increased intestinal permeability for bacterial lipopolysaccharides (LPS) in response to the consumption of high-fat diets resulting in an elevated systemic LPS level and low-grade inflammation. Animal studies indicate differences in the physiologic effects of fermentable and non-fermentable dietary fibres as well as differences in long- and short-term effects of fermentable dietary fibre. The human intestinal microbiome is enriched in genes involved in the degradation of indigestible polysaccharides. The extent to which dietary fibres are fermented and in which molar ratio SCFA are formed depends on their physicochemical properties and on the individual microbiome. Acetate and propionate play an important role in lipid and glucose metabolism. Acetate serves as a substrate for de novo lipogenesis in liver, whereas propionate can be utilised for gluconeogenesis. The conversion of fermentable dietary fibre to SCFA provides additional energy to the host which could promote obesity. However, epidemiologic studies indicate that diets rich in fibre rather prevent than promote obesity development. This may be due to the fact that SCFA are also ligands of free fatty acid receptors (FFAR). Activation of FFAR leads to an increased expression and secretion of enteroendocrine hormones such as glucagon-like-peptide 1 or peptide YY which cause satiety. In conclusion, the role of SCFA in host energy balance needs to be re-evaluated.

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... 15 Although much of the ensuing research investigating the involvement of gut microbes in the establishment and maintenance of obesity comes from pre-clinical mouse models, the successful transfer of an obese phenotype from humans via faecal transplant suggests there might be a common mechanism between mice and humans. 9 Long-term weight gain in humans has also been associated with lower microbial diversity, which is further exacerbated by inadequate dietary fibre intake. 16 Microbiota diversity is measured as the number and relative distribution of microbial species that are present, where lower diversity is generally regarded as a marker of dysbiosis (ie, microbial imbalance). ...
... 19,20 This finding is not consistent, however, with research indicating that fibre-and SCFA-rich diets could potentially prevent obesity onset. 9 As opposed to the function of SCFAs serving as additional energy supplies and adipogenic factors, researchers instead hypothesise that SCFAs derived from dietary fibre could be beneficial in obesity prevention, such as through regulating satiety responses and lipid metabolism 10 and by decreasing the total energy density of the diet. 9 Both butyrate and propionate may also exert beneficial effects on glucose metabolism by inducing gluconeogenesis, which may be related to improved glucose tolerance 21 and by improving insulin sensitivity. ...
... 9 As opposed to the function of SCFAs serving as additional energy supplies and adipogenic factors, researchers instead hypothesise that SCFAs derived from dietary fibre could be beneficial in obesity prevention, such as through regulating satiety responses and lipid metabolism 10 and by decreasing the total energy density of the diet. 9 Both butyrate and propionate may also exert beneficial effects on glucose metabolism by inducing gluconeogenesis, which may be related to improved glucose tolerance 21 and by improving insulin sensitivity. 22 As such, while SCFAs are involved in energy harvesting and regulating host metabolism, there is research to indicate that these metabolites may confer a protective role in the onset of obesity, warranting further attention in the context of weight regulation. ...
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Emerging evidence indicates that the gut microbiota relate to the onset and maintenance of obesity via several pathophysiological mechanisms, all of which are influenced by the host diet. The rapid shift towards Western-typical diets at a global scale may be contributing to gut dysbiosis, and consequently fuelling the global obesity crisis. Further mechanistic understanding of the influence of the gut microbiota in weight regulation in humans may lend itself to the development of more efficacious treatments.
... Bakterie zamieszkujące jelito grube należą do pięciu głównych grup: Firmicutes (głównie Clostridium, Eubacterium, Faecalibacterium), Bacteroidetes (głównie Alistipes, Bacteroides, Parabacteroides, Prevotella), Actinobacteria (Bifidobacterium), Proteobacteria (głównie Escherichia coli), Verrucomicrobia (Akkermansia) i Fusobacteria; przy czym dominują bakterie należące do dwóch pierwszych wymienionych typów (4). Skład mikrobiomu nie jest stały a ulega ciągłym zmianom, dostosowując się do ewoluujących warunków (1,2,(4)(5)(6)(7)(8)(9)(10). W literaturze nadorganizm tworzony przez gospodarza i kolonizujące go organizmy symbiotyczne nazywany jest "holobiontem" aby zwrócić uwagę na zależność każdej ze składowych od siebie nawzajem (11). ...
... Przekłada się to na niepotrzebne pobudzenie procesów związanych ze stanem zapalanym. Wzrasta ryzyko chorób mający tło zakrzepowe, zaburzeń metabolizmu glukozy, chorób mikro-i makronaczyniowych (4). ...
... Choroby metaboliczne, takie jak otyłość, są związane z obniżeniem różnorodności gatunkowej jelitowego mikrobiomu; u osób otyłych spada poziom bakterii typu Bacetroidetes w stosunku do Firmicutes (7). Co istotne, spadek masy ciała prowadzi do odwrócenia się podanej zależności i wzrostu liczebności populacji Bacteroidetes (4,7,12,20,21). Jest to ważne ponieważ bakterie typu Firmicutes zapewniają dodatkowe substancje energetyczne organizmowi gospodarza, co według niektórych autorów, może być związane z promowaniem wzrostu masy ciała przez zmieniony chorobą mikrobiom (7). Dodatkowo warte zaznaczenia jest to, że u pacjentów po operacjach bariatrycznych samoistnie odtwarza się prawdopodobnie korzystny stosunek Firmicutes do Bacteroidetes (7,10). ...
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Introduction and purpose: The growing number of obese people is one of the greatest problems of modern medicine. It is estimated that every 10th person is obese. Recent studies also suggest that the gut microbiome may contribute to the pathogenesis of obesity. Description of the state of knowledge: Microbiota is named a super organ that has the ability to evolve in response to changing conditions within the host organism. It is named so because it is made up of over 100,000 billion cells that belong to different groups of organisms. Microbiota consists of bacteria, fungi, protists, viruses and archaea. This taxonomically diverse collective plays a vital role in maintaining the homeostasis of the human body. A well-balanced intestinal flora protects the digestive tract from colonization by pathogenic microorganisms, it is also important in maintaining the integrity of the intestinal walls, is involved in the synthesis of certain vitamins and plays a role in nourishing mucosa cells. Moreover, it is known that the microflora can influence body weight, insulin sensitivity, and metabolism of certain sugars and lipids. Disturbances in the composition of the microbiome (dysbiosis) lead to an increased absorption of short-chain fatty acids, which leads to an increase in endogenous YY peptide synthesis. This protein slows down the intestinal transit and indirectly leads to increased absorption of nutrients. This predisposes to the development of obesity. The use of prebiotics, probiotics and some antibiotics reduces intestinal dysbiosis. For obese patients, it is associated with reduction of insulin resistance and decrease in blood glucose level. Conclusions: In the light of the available studies, it can be concluded that intestinal dysbiosis may play a role in the pathogenesis of obesity. Unfortunately, the practical application of this knowledge is not yet well documented. Therefore this topic requires further experiments and analysis.
... Further research demonstrated that the combination of fungal proteins from H. erinaceus and 5-fluoro-2, 4(1H, 3H)-pyrimidinedione (5-Fu) has anti-tumor effects. The fungal proteins mainly show auxiliary antitumor effects, which can ameliorate the dysbacteriosis induced by 5-Fu (Blaut, 2015). HEP can inhibit certain aerobic and microaerobic bacteria such as Flavobacteriaceae, Parabacteroides, Anoxybacillus, Christensenellaceae, Aggregatibacter, Planococcaceae, Comamonadaceae, Desulfovibrionaceae, Staphylococcus, Bilophila, Aerococcaceae, and Sporosarcina in xenografted mice. ...
... The application of 5-Fu exacerbates dysbacteriosis, resulting in highly imbalanced levels of the phyla Actinobacteria and TM7, which reduces its antitumor effects. Fungal proteins from H. erinaceus show auxiliary and prophylactic effects on the gut microbiota in mice with xenografted tumors, and when combined with 5-Fu, were able to reduce microbiota imbalances (Blaut, 2015). In a murine breast cancer model, the administration of paclitaxel (a first-line chemotherapy reagent for breast cancer) in combination with polysaccharides derived from G. lucidum spores (SGP) resulted in improved tumor control. ...
... H. erinaceus polysaccharides combined with Bifidobacterium treatment significantly enhanced the settling of Bifidobacterium and restored all cytokines to near normal levels in an IBD mouse model (Diling et al., 2017). H. erinaceus proteins significantly promoted the engraftment of Bifidobacterium, and produced an obvious increase in the relative abundance of Bifidobacterium and other probiotics, as well as enhanced immunity (Blaut, 2015). The application of edible mushrooms in combination with therapeutic interventions appears to have promise, but there are not many reports in this area, and further research is needed to explore this potential. ...
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Edible mushrooms as valuable health foods have potential beneficial effects, and these beneficial activities are connected with the modulation of gut microbiota. In this review, we discuss the regulation of gut microbiota by edible mushroom. Ganoderma lucidum increases Bacteroides/Firmicutes ratio, and promote the growth of anti-inflammatory and short-chain fatty acid (SCFA) producing bacteria. Hericium erinaceus maintains intestinal barrier integrity, and increases the diversity and richness of gut microbiota. Lentinula edodes act as a prebiotic, increases SCFA-producing bacteria and regulates the proportion of Bacteroides/Firmicutes. Grifola frondosa increases the ratio of Bacteroides/Firmicutes, the growth of anti-inflammatory and SCFA-producing bacteria. We also discuss the effects of different edible mushrooms on the gut microbiota in different diseases and introduce a perspective application of mushrooms as adjuvant therapies for modulating gut microbiota in clinical treatments. Summarized, the statement in modulation of gut microbiota composition by edible mushrooms will provide a new perspective for further research.
... Its role is, among other things, to distinguish between commensal and pathogenic bacteria and to adjust the reaction depending on the diagnosis. When the intestinal microbiota is disturbed, as a result of, e.g., antibiotics, ionizing radiation, prolonged severe stress or a poor diet (rich in fats and monosaccharides) [48][49][50], the consequences may be a loss of intestinal barrier tightness, reduced production of B vitamins and anti-inflammatory substances (e.g., SCFA, Short-Chain Fatty Acids) and intensification of pro-inflammatory ones, e.g., LPS (Lipopolysaccharide) endotoxins [49,51,52]. As a result, these changes may lead to an increase in chronic inflammation, endotoxemia, an increase in the risk of infection and an increase in bloating and peristalsis disorders. ...
... Its role is, among other things, to distinguish between commensal and pathogenic bacteria and to adjust the reaction depending on the diagnosis. When the intestinal microbiota is disturbed, as a result of, e.g., antibiotics, ionizing radiation, prolonged severe stress or a poor diet (rich in fats and monosaccharides) [48][49][50], the consequences may be a loss of intestinal barrier tightness, reduced production of B vitamins and anti-inflammatory substances (e.g., SCFA, Short-Chain Fatty Acids) and intensification of pro-inflammatory ones, e.g., LPS (Lipopolysaccharide) endotoxins [49,51,52]. As a result, these changes may lead to an increase in chronic inflammation, endotoxemia, an increase in the risk of infection and an increase in bloating and peristalsis disorders. ...
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Colorectal cancer is one of the most common cancers in Europe and the world. Cancer treatments have side effects and cause significant deterioration of the patient’s nutritional status. Patient malnutrition may worsen the health condition and prevent the deliberate effects of the therapy. The aim of this review was to describe the available data about clinical nutrition in colorectal cancer patients. A large proportion of colorectal cancer patients suffer from malnutrition, which negatively affects the survival prognosis, quality of life, and oncological therapy. Therefore, monitoring nutritional status during the treatment is essential and can be used to arrange proper nutritional therapy to enhance patient responses, prevent side effects, and shorten recovery time. The principles of nutrition during anticancer therapy should mainly consider light and low-fat foods, the exclusion of lactose and gluten-containing foods in certain cases, or the introduction of special dietary products such as oral nutrition supplements and it should be tailored to patients’ individual needs.
... Mainly, microbiota benefits the host through intestinal epithelium by protecting it and producing beneficial metabolites, which helps in food digestion and against pathogenic invasion. The gut microbiome can convert fermentable dietary fibers into short-chain fatty acids (SCFA) that provide additional energy to the host (Blaut, 2015). These SCFA are organic carboxylic acids with less than 6 carbon atoms of the acetate; propionate and butyrate are the most abundant extension in the intestine (Alam et al., 2000). ...
... The intestinal microbiota is also considered an additional organ, which comprises billions of microorganisms. The intestinal microbiota is important in the synthesis and metabolism of nutrients, hormones, and vitamins, playing a role in drug utilization, pathogen fortification, and immune system maturation (Blaut, 2015;Mangiola et al., 2016;Rinninella et al., 2019). Therefore, the imbalance of intestinal microbiota may lead to serious diseases. ...
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Short-chain fatty acids (SCFA) are principal nutrient substrates of intestinal epithelial cells that regulate the epithelial barrier in yaks. Until now, metagenomics sequencing has not been reported in diarrheal yaks. Scarce information is available regarding the levels of fecal SCFA and diarrhea in yaks. So, our study aims to identify the potential pathogens that cause the emerging diarrhea and explore the potential relationship of short-chain fatty acids in this issue. We estimated diarrhea rate in yaks after collecting an equal number of fecal samples from affected animals. Metagenomics sequencing and quantitative analysis of SCFA were performed, which revealed 15%-25% and 5%-10% prevalence of diarrhea in yak's calves and adults, respectively. Violin box plot also showed a higher degree of dispersion in gene abundance distribution of diarrheal yaks, as compared to normal yaks. We found 366,163 significant differential abundance genes in diarrheal yaks, with 141,305 upregulated and 224,858 downregulated genes compared with normal yaks via DESeq analysis. Metagenomics binning analysis indicated the higher significance of bin 33 (Bacteroidales) (p < 0.05) in diarrheal animals, while bin 10 (p < 0.0001), bin 30 (Clostridiales) (p < 0.05), bin 51 (Lactobacillales) (p < 0.05), bin 8 (Lachnospiraceae) (p < 0.05), and bin 47 (Bacteria) (p < 0.05) were significantly higher in normal yaks. At different levels, a significant difference in phylum (n = 4), class (n = 8), oder (n = 8), family (n = 16), genus (n = 17), and species (n = 30) was noticed, respectively. Compared with healthy yaks, acetic acid (p < 0.01), propionic acid (p < 0.01), butyric acid (p < 0.01), isobutyric acid (p < 0.01), isovaleric acid (p < 0.05), and caproic acid (p < 0.01) were all observed significantly at a lower rate in diarrheal yaks. In conclusion, besides the increased Staphylococcus aureus, Babesia ovata, Anaplasma phagocytophilum, Bacteroides fluxus, viruses, Klebsiella pneumonia, and inflammation-related bacteria, the decrease of SCFA caused by the imbalance of intestinal microbiota was potentially observed in diarrheal yaks.
... Another consequence of dysbiosis is the altered production of short-chain fatty acids (SCFA). They are produced by the microbial fermentation of undigested carbohydrates, but the amount of SCFA depends on various factors in the host microbiota [189]. Butyrate, propionate and acetate, which make up 90-95% of SCFAs found in the colon, act as signaling ligands between the gut microbiota and host metabolism at specific levels [189][190][191]. ...
... They are produced by the microbial fermentation of undigested carbohydrates, but the amount of SCFA depends on various factors in the host microbiota [189]. Butyrate, propionate and acetate, which make up 90-95% of SCFAs found in the colon, act as signaling ligands between the gut microbiota and host metabolism at specific levels [189][190][191]. ...
Article
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Pesticides have long been used in agriculture and household treatments. Pesticide residues can be found in biological samples for both the agriculture workers through direct exposure but also to the general population by indirect exposure. There is also evidence of pesticide contamination in utero and trans-generational impacts. Whilst acute exposure to pesticides has long been associated with endocrine perturbations, chronic exposure with low doses also increases the prevalence of metabolic disorders such as obesity or type 2 diabetes. Dysmetabolism is a low-grade inflammation disorder and as such the microbiota plays a role in its etiology. It is therefore important to fully understand the role of microbiota on the genesis of subsequent health effects. The digestive tract and mostly microbiota are the first organs of contact after oral exposure. The objective of this review is thus to better understand mechanisms that link pesticide exposure, dysmetabolism and microbiota. One of the key outcomes on the microbiota is the reduced Bacteroidetes and increased Firmicutes phyla, reflecting both pesticide exposure and risk factors of dysmetabolism. Other bacterial genders and metabolic activities are also involved. As for most pathologies impacting microbiota (including inflammatory disorders), the role of prebiotics can be suggested as a prevention strategy and some preliminary evidence reinforces this axis.
... 8 Recently, there have been numerous pieces of evidence suggesting that the gut microbiota plays a crucial role in the pathophysiology of obesity by modulating energy homeostasis. [9][10][11] In the gut microbiota, trillions of microbes composed of 1000-1100 different bacterial species are densely colonized and they contribute to nutrient absorption and energy regulation. 10,12 The gut microbial phyla consist of Actinobacteria, Cyanobacteria, Proteobacteria, Tenericutes, and Verrucomicrobia, with the two dominant phyla being Firmicutes and Bacteriodetes. ...
... [9][10][11] In the gut microbiota, trillions of microbes composed of 1000-1100 different bacterial species are densely colonized and they contribute to nutrient absorption and energy regulation. 10,12 The gut microbial phyla consist of Actinobacteria, Cyanobacteria, Proteobacteria, Tenericutes, and Verrucomicrobia, with the two dominant phyla being Firmicutes and Bacteriodetes. 13 The Firmicutes to Bacteriodetes ratio (F/B ratio) has been extensively examined in the human and mouse gut microbiota and is positively correlated with the occurrence of obesity. ...
Article
Obesity is an increasing health problem worldwide as it is the major risk factor for metabolic diseases. In the present study, we investigated the anti-obesity effects of WHS by examining its effects on high fat diet (HFD)-induced obese mice. Male C57BL/6 mice were fed either a normal diet (ND) or a high fat diet (HFD) with or without WHS. At the end of the experiment, we observed the changes in their body weight and white adipose tissue (WAT) weight and lipid profiles in plasma. We performed western blot and histological analyses of WAT and liver to elucidate the molecular mechanisms of action. We also conducted fecal 16S rRNA analysis for investigating the gut microbiota. Our results indicated that pre- and post-oral administration of WHS significantly prevented body weight gain and reduced body fat weight in HFD-induced obese mice. In addition, WHS was found to improve adipocyte hypertrophy and liver fat accumulation by regulating the AMPK and AKT/mTOR pathways. WHS ameliorated hyperlipidemia by reducing total cholesterol and low-density lipoprotein (LDL) and decreased the energy metabolism-related hormones, leptin and insulin, in mouse plasma. Furthermore, we found that WHS modulated gut dysbiosis by normalizing HFD-induced changes. Taken together, our in vivo data implicate that WHS can be considered as a potential dietary supplement for alleviating obesity.
... [38] They also increase intestinal transit by activating leptin, peptide YY and glucagon-like peptide. [39] 5HT produced by the ECCs under influence of SCFAs and 2BA needs dietary tryptophan as the same isn't produced in the body. Hence, brain regulation by 5HT occurs in response to exogenous tryptophan only. ...
... These findings suggest that the gut microbiota may efficiently harvest energy from a given diet and act as a crucial environmental factor in regulating energy harvesting, storage, and expenditure [31,32,34]. Other mechanisms that explain how gut dysbiosis mediates obesity pathophysiology include increased intestinal permeability accompanied with metabolic endotoxemia, dysregulated gut immunity, contribution to low-grade systemic inflammation, and hormonal imbalance in the gut-brain-adipose axis [58][59][60][61][62]. Furthermore, particular gut microbial metabolites such as short-chain fatty acids (SCFAs), the majority of which include acetate, propionate, and butyrate, could also contribute to host energy homeostasis and have been extensively investigated in this context [63][64][65][66][67][68][69][70][71]. ...
Article
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Obesity is a global public health issue and major risk factor for pathological conditions, including type 2 diabetes, dyslipidemia, coronary artery disease, hepatic steatosis, and certain types of cancer. These metabolic complications result from a combination of genetics and environmental influences, thus contributing to impact whole-body homeostasis. Mechanistic animal and human studies have indicated that an altered gut microbiota can mediate the development of obesity, leading to inflammation beyond the intestine. Moreover, prior research suggests an interaction between gut microbiota and peripheral organs such as adipose tissue via different signaling pathways; yet, to what degree and in exactly what ways this inter-organ crosstalk modulates obesity remains elusive. This review emphasizes the influence of circulating gut-derived short chain fatty acids (SCFAs) i.e., acetate, propionate, and butyrate, on adipose tissue metabolism in the scope of obesity, with an emphasis on adipocyte physiology in vitro and in vivo. Furthermore, we discuss some of the well-established mechanisms via which microbial SCFAs exert a role as a prominent host energy source, hence regulating overall energy balance and health. Collectively, exploring the mechanisms via which SCFAs impact adipose tissue metabolism appears to be a promising avenue to improve metabolic conditions related to obesity.
... The intestinal microbiota comprises bacteria, viruses, fungi, and other microorganisms in the gut, where the bacteria account for 95% of the total microbial flora. Intestinal flora imbalance occurs when the stability and diversity of the intestinal bacterial community are destroyed (Yılmaz and Eren, 2017) and can affect the number and function of intestinal SCFAs (Carter and Karpen, 2007;Blaut, 2014). SCFAs being the major metabolite of intestinal flora, can promote intestinal epithelial proliferation and minimize the intestinal epithelial cells' apoptosis, thereby increasing the expression of tight junction (TJ) proteins to reduce intestinal mucosa permeability (Gui and Shen, 2016;Zhao et al., 2018). ...
Article
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Background and aims Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease with a high incidence, and the situation is not optimistic. Intestinal flora imbalance is strongly correlated with NAFLD pathogenesis. Zhishi Daozhi Decoction (ZDD) is a water decoction of the herbs used in the classical Chinese medicine prescription Zhishi Daozhi Pills. Zhishi Daozhi Pills has shown promising hepatoprotective and hypolipidemic properties, but its specific mechanism remains unclear. Methods Mice were fed on a high fat-rich diet (HFD) for ten weeks, and then the animals were administrated ZDD through oral gavage for four weeks. The serum liver function and blood lipid indexes of the mice were then tested using an automatic biochemical analyzer. H&E and Oil Red O staining were used to observe the pathological conditions of mice liver tissue, and 16S rRNA sequencing technology was used to analyze the changes in intestinal flora of mice. The concentration of short-chain fatty acids (SCFAs) in the gut of mice was analyzed by gas chromatography-mass spectrometry (GC-MS). The expression of tight junction (TJ) proteins between ileal mucosal epithelial cells was analyzed using the immunofluorescence technique. Results ZDD was found to reduce the bodyweight of NAFLD mice, reduce serum TG, CHO, ALT, and AST levels, reduce fat accumulation in liver tissue, make the structure of intestinal flora comparable to the control group, and increase the concentration of intestinal SCFAs. It was also found to increase the expression of TJ proteins such as occludin and ZO-1, making them comparable to the control group. Conclusions ZDD has a therapeutic effect on NAFLD mice induced by HFD, which may act by optimizing the intestinal flora structure.
... The present study showed that the main SCFAs in jejunal and ileal contents were acetate and butyrate, while those in colonic contents were acetate, propionate, and butyrate. Acetate participates in energy generation and lipogenesis for all types of tissues [34]. Butyrate increases energy expenditure and prevents diet-induced fat accumulation and insulin resistance [35]. ...
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Background Maternal gut microbiota and metabolites are associated with their offspring’s health. Our previous study showed that maternal body fat percentage increased from days 45 to 110 of gestation in a Huanjiang mini-pig model. Thus, this study aimed to investigate the changes in gut microbiota composition and microbial metabolite profile of sows from days 45 to 110 of gestation. Results Twenty-four Huanjiang mini-pigs with average body weight were assigned for sample collection during early- (day 45 of pregnancy), mid- (day 75 of pregnancy), and late-pregnancy (day 110 of pregnancy). The results showed that the relative abundances of Clostridium_sensu_stricto _ 1 , Romboutsia , Turicibacter , and Streptococcus in jejunal contents were higher at day 110 than those at day 45 or 75 of gestation. In the ileum, the relative abundance of Streptococcus was higher ( P < 0.05) at day 110 of gestation, as well as the metabolism function of the jejunal and ileal microbiota. The ileal butyrate and acetate concentrations were higher at days 45 and 110 of gestation, respectively. In the colon, the concentrations of cadaverine and spermine were higher ( P < 0.05) at days 45 and 110 of gestation, respectively. Metabolomic analyses demonstrated that the metabolic pathways, including D-glutamine and D-glutamate metabolism, phenylalanine/tyrosine/tryptophan biosynthesis, and alanine/aspartate/glutamate metabolism changed during gestation. Conclusion Collectively, our results showed that gut microbiota composition and microbial metabolites changed dramatically from early to late pregnancy in a Huanjiang mini-pig model. These findings will provide new targets in formulating maternal nutritional interventions to alleviate the adverse effects during pregnancy on offspring health outcomes.
... In addition, on day 28 of age, ultra-early weaning led to an increase in bacteria related to the production of short-chain fatty acids (SCFA), such as Agathobacter (Horvath et al., 2021), Prevotellaceae_NK3B31_group (Shang et al., 2021), Prevotella (Yang et al., 2018), and Phascolarctobacterium (Yang et al., 2018). The production of SCFA is important in energy homeostasis (Schwiertz et al., 2010;Blaut, 2015). In addition, ultra-early weaning led to an increase in intestinal Prevotellaceae_UCG-003, which is closely related to polysaccharide, protein, energy, and vitamin metabolism (Cui et al., 2022), and a decrease in Desulfovibrio and Christensenellaceae_R.7_group, which are the bacteria involved in inducing bowel disease (Marini et al., 2002;Mancabelli et al., 2017). ...
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Piglets with the same genetic background were used to investigate the effects of different lengths of suckling period on growth performance, hematology parameters, and fecal microbiota. All piglets were born by a sow (Landrace×Yorkshire). On day 14 postpartum, a total of 16 piglets [Duroc×(Landrace×Yorkshire)] with a similar initial body weight (2.48 ± 0.25 kg) were randomly assigned into two groups with four replicates per group, two pigs per replicate pen (one barrow and one gilt). On day 14 of age, experiment started, piglets from the first group were weaned (14W), whereas the others continued to receive milk until day 28 of age (28W). The experiment completed on day 70 of age, last 56 days. Growth performance parameters including body weight, average daily gain, feed intake, feed efficiency, and growth rate and hematology parameters including immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), albumin, globulin, and total protein were measured in this study. Additionally, a technique of 16S rRNA gene sequencing was used to analyze fecal microbiota for revealing how the changes in the lengths of suckling period on intestinal microbiota. We found that ultra-early weaning impaired growth performance of piglets, whose worse body weight, average daily gain, feed intake, feed efficiency, and growth rate were observed in 14W group at all measured timepoints in comparison with those in 28W group (P < 0.05). Moreover, higher contents of serum IgA (P = 0.028), IgG (P = 0.041), and IgM (P = 0.047), as well as lower contents of serum albumin (P = 0.002), albumin-to-globulin ratio (P = 0.003), and total protein (P = 0.004), were observed in 14W group in comparison with those in 28W group on day 28 of age, but not on day 70 of age. High-throughput pyrosequencing of 16S rRNA indicated that the intestinal microbiota richness in 14W group was lower than that in 28W group (P < 0.05); moreover, in comparison with 28W group at all sampling timepoints, fecal microbiota in 14W group showed more beneficial bacteria and fewer pathogenic bacteria (P < 0.05). Therefore, we considered that ultra-early weaning had positive effects on immune status and fecal microbiota composition in piglets, but negative effects on growth performance and fecal microbiota abundance.
... In addition, data acquisition was done over a 24-h period, which does not fully reflect the long-term effects of a four-month diet. Moreover, possible differences in the gut microbiota-produced energy [27,28], which could be modified in the absence of PLTP, have been overlooked in our EE measurements. Lastly, compared to WT, Pltp-KO mice display a higher adipose (low metabolic activity) to lean (high metabolic activity) mass ratio. ...
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Bacterial lipopolysaccharides (LPS, endotoxins) are found in high amounts in the gut lumen. LPS can cross the gut barrier and pass into the blood (endotoxemia), leading to low-grade inflammation, a common scheme in metabolic diseases. Phospholipid transfer protein (PLTP) can transfer circulating LPS to plasma lipoproteins, thereby promoting its detoxification. However, the impact of PLTP on the metabolic fate and biological effects of gut-derived LPS is unknown. This study aimed to investigate the influence of PLTP on low-grade inflammation, obesity and insulin resistance in relationship with LPS intestinal translocation and metabolic endotoxemia. Wild-type (WT) mice were compared with Pltp-deficient mice (Pltp-KO) after a 4-month high-fat (HF) diet or oral administration of labeled LPS. On a HF diet, Pltp-KO mice showed increased weight gain, adiposity, insulin resistance, lipid abnormalities and inflammation, together with a higher exposure to endotoxemia compared to WT mice. After oral administration of LPS, PLTP deficiency led to increased intestinal translocation and decreased association of LPS to lipoproteins, together with an altered catabolism of triglyceride-rich lipoproteins (TRL). Our results show that PLTP, by modulating the intestinal translocation of LPS and plasma processing of TRL-bound LPS, has a major impact on low-grade inflammation and the onset of diet-induced metabolic disorders.
... 50 Acetate in particular has generated a fair amount of controversial literature about its benefits versus detrimental effects on host metabolic health. [51][52][53][54] Acetate arising from gut microbiota metabolism is absorbed by colonocytes and transported to the liver where a portion of it is available for lipogenesis and cholesterol synthesis. 55 However, most microbiota-generated acetate exits the liver and enters peripheral circulation for uptake by adipose and muscle tissue 55 where it is then either oxidized to produce ATP or used as a substrate for de novo lipogenesis depending on energy needs. ...
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Little is known about how interactions among grain processing, grain type, and carbohydrate utilization (CU) by the microbiome influence the health benefits of whole grains. Therefore, two whole grains – brown rice and whole wheat – and two processing methods – boiling (porridge) and extrusion – were studied for their effects on host metabolic outcomes in mice harboring human microbiomes previously shown in vitro to have high or low CU. Mice carrying either microbiome experienced increases in body weight and glycemia when consuming Western diets supplemented with extruded grains versus porridge. However, mice with the high but not low CU microbiome also gained more weight and fat over time and were less glucose tolerant when consuming extruded grain diets. In high CU microbiome mice, the exacerbated negative health outcomes associated with extrusion were related to altered abundances of Lachnospiraceae and Ruminococcaceae as well as elevated sugar degradation and colonic acetate production. The amplicon sequence variants (ASVs) associated with extruded and porridge diets in this in vivo study were not the same as those identified in our prior in vitro study; however, the predicted functions were highly correlated. In conclusion, mice harboring both high and low CU microbiomes responded to the whole grain diets similarly, except the high CU microbiome mice exhibited exacerbated effects due to excessive acetate production, indicating that CU by the microbiome is linked to host metabolic health outcomes. Our work demonstrates that a greater understanding of food processing effects on the microbiome is necessary for developing foods that promote rather than diminish host health.
... 46 Acetate in particular has generated a fair amount of controversial literature about its bene ts versus detrimental effects on host metabolic health. 47,48,49,50 Acetate arising from gut microbiota metabolism is absorbed by colonocytes and transported to the liver where a portion of it is available for lipogenesis and cholesterol synthesis. 51 However, most microbiota-generated acetate exits the liver and enters peripheral circulation for uptake by adipose and muscle tissue 51 where it is then either oxidized to produce ATP or used as a substrate for de novo lipogenesis depending on energy needs. ...
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Background: Grain processing, grain type, and carbohydrate utilization (CU) by the microbiome each individually influence the health benefits of whole grains. However, little is known about how these factors interact to influence host health outcomes. Therefore, two whole grains, brown rice and whole wheat, and two processing methods, boiling (porridge) and extrusion, were studied for their effects on host metabolic outcomes in mice harboring human microbiomes previously shown in vitro to have high or low CU. Results: Mice carrying either microbiome experienced increases in body weight and glycemia when consuming Western diets supplemented with extruded grains versus porridge. However, mice with the high CU but not low CU microbiome also gained more body weight and fat over time and were less glucose tolerant when consuming extruded grain diets. Cluster analysis of both host metabolic health parameters and fecal microbiota changes during feeding revealed that mice consuming extruded diets clustered seprately from those consuming the other diets only when harboring the high CU microbiome, suggesting that the exacerbated negative host health outcomes associated with extrusion were related to changes in microbiota composition. In partiuclar, the high CU microbiome mice consuming an extruded diet had altered abundances of Lachnospiraceae and Ruminococcaceae, which contributed to elevated sugar degradation and colonic acetate production. The ASVs associated with the extruded and porridge diets in this in vivo study were not the same as those identified in our prior in vitro study; however, the predicted functions were highly correlated. Conclusions: Grain processed using severe extrusion, regardless of grain type, worsened host metabolic health compared with grain processed to porridge. Mice harboring either microbiome responded to the whole grain diets similarly, except the high CU microbiome mice exhibited exacerbated effects due to excessive acetate production, indicating that CU by the microbiome is linked to host metabolic health outcomes. Importantly, the metabolic phenotypes observed in the present study were predictable based on the results from our in vitro study. Our work demonstrates that a greater understanding of food processing effects on the microbiome is necessary for developing foods that promote rather than diminish host health.
... The gut microbiota plays a crucial role in NAFLD mitigation through various mechanisms such as energy absorption and storage, promoting insulin resistance and choline deficiency and interfering with bile acid metabolism (Blaut, 2015;Wang et al., 2020). Hence, we analyzed the changes of the gut microbiota in NAFLD with TF3 supplement and found that the community richness and diversity of the gut microbiota increased. ...
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Nonalcoholic fatty liver disease (NAFLD), one of the risk factors for hepatitis, cirrhosis, and even hepatic carcinoma, has been a global public health problem. The polyphenol compound theaflavin-3,3′-digallate (TF3), mainly extracted from black tea, has been reported to produce an effect on hypoglycemic and antilipid deposition in vitro . In our study, we further investigated the function and novel mechanisms of TF3 in protecting NAFLD in vivo . By using leptin-deficient obese (ob/ob) mice with NAFLD symptoms, TF3 treatment prevented body weight and waistline gain, reduced lipid accumulation, and alleviated liver function injury, as well as decreased serum lipid levels and TG levels in livers in ob/ob mice, observing no side effects. Furthermore, the transcriptome sequencing of liver tissue showed that TF3 treatment corrected the expression profiles of livers in ob/ob mice compared with that of the model group. It is interesting to note that TF3 might regulate lipid metabolism via the Fads1/PPARδ/Fabp4 axis. In addition, 16S rRNA sequencing demonstrated that TF3 increased the abundance of Prevotellaceae_UCG-001 , norank_f_Ruminococcaceae , and GCA-900066575 and significantly decreased that of Parvibacter. Taken together, the effect of TF3 on NAFLD might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota. TF3 might be a promising candidate for NAFLD therapy.
... In this study, the proportion of Lactobacillus in the intestinal tract of three-breed hybrid pigs 3 BioMed Research International at different ages was the highest, which was closely related to the function of Lactobacillus in regulating animal immunity, maintaining bacterial homeostasis and body health, assisting digestion, and improving the growth rate of growing pigs [37,46]. Oscillospira and Prevotella are two important short-chain fatty acid-producing bacteria, which can BioMed Research International decompose resistant starch and feed fiber and other indigestion substances and produce short-chain fatty acids and other products, playing an important role in energy balance [47,48]. Oscillospira is closely related to body health [49], and Prevotella is the main bacteria that mainly digest dietary fiber [50]. ...
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The changes of intestinal microbiota are closely related to the growth and development of animals. The current study is aimed at exploring the composition of the microbial community of pigs at different growth stages. Fresh fecal samples of three-breed hybrid pigs at three developmental stages (60, 120, and 180 days of age) were collected. The microbial composition was analyzed based on the 16S rDNA gene of bacteria Illumina NovaSeq sequencing platform. The results showed that the intestinal microbiota of pigs was distributed in 22 phyla, 46 classes, 84 orders, 147 families, and 287 genera. Firmicutes, Bacteroides, Spirochaetae, Proteobacteria, and Actinobacteria were the dominant phyla. Lactobacillus, Streptococcus, SMB53, Oscillospira, and Prevotella were the dominant genera. Among them, the abundance of Lactobacillus and SMB53 increased first and then decreased, while the change of Oscillospira was opposite. In addition, the abundance of Streptococcus increased while that of Prevotella decreased gradually. Moreover, with the increase of time and body weight, the microbial diversity showed a decreasing trend. In conclusion, the intestinal microbial composition of the three-breed hybrid pigs was relatively stable during the fattening stage, but there were significant differences in abundance.
... The gut microbiota interacts with the host through several mechanisms including the production of short chain fatty acids (SCFAs), including acetate, butyrate and propionate, that are the byproducts of fermentation of non-digestible starches and fibers in the large intestine. SCFAs serve as energy substrates (Bergman, 1990;Brown et al., 2003;Louis et al., 2010;Blaut, 2015) and mediate crosstalk between bacteria and host metabolism (Manco et al., 2010). For example, they activate the mucosal G protein-coupled receptors (GPR) GPR-43 and GPR-41 to regulate secretion of incretin hormones such as glucagon like peptide-1 (GLP-1) (Nøhr et al., 2013;Kimura et al., 2014;Le Poul et al., 2003) and peptide YY (PYY) (Carvalho and Abdalla Saad, 2013), and adipose tissue-derived leptin. ...
Article
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Evidence suggests that type 1 diabetes (T1D) risk and progression are associated with gut bacterial imbalances. Children with either T1D or islet antibody positivity exhibit gut dysbiosis (microbial imbalance) characterized by lower gram-positive to gram-negative gut bacterial ratios compared to healthy individuals, leading to a pro-inflammatory milieu. In addition, specific gut microbiome changes, including increased virulence factors, elevated phage, prophage, and motility genes, and higher amplitude stress responses, have been identified in individuals who have or are progressing towards T1D. Additionally, gut microbiome differences are associated with and thought to contribute to obesity, a comorbidity that is increasingly prevalent among persons with T1D. Obesity in T1D is problematic because individuals with obesity progress faster to T1D, have reduced insulin sensitivity compared to their lean counterparts, and have higher risk of complications. Animal and human studies suggest higher relative abundance of bacterial taxa associated with changes in bile acid and short chain fatty acid biosynthesis in obesity. However, it is unknown to what extent the gut microbiome plays a role in obesity in T1D and these worse outcomes. In this review, we aim to evaluate potential gut microbiome changes and associations in individuals with T1D who are obese, highlighting the specific gut microbiome changes associated with obesity and with T1D development. We will identify commonalities and differences in microbiome changes and examine potential microbiota-host interactions and the metabolic pathways involved. Finally, we will explore interventions that may be of benefit to this population, in order to modify disease and improve outcomes.
... In addition, data acquisition was done over a 24-hour period which does not fully reflect the longterm effect of a four-month diet. Moreover, possible differences in gut microbiota-produced energy (34,35), which could be modified in the absence of PLTP, have been overlooked in our EE measurements. Lastly, compared to WT, Pltp-KO mice display a higher adipose (low metabolic activity) to lean (high metabolic activity) mass ratio. ...
Thesis
Les LPS (lipopolysaccharides), endotoxines provenant des bactéries à Gram négatif, sont connus pour avoir la capacité d’interagir avec la barrière intestinale et provoquer la désorganisation de cette dernière. Ces molécules sont ensuite capables de passer dans le compartiment sanguin (endotoxémie) pour provoquer une inflammation métabolique à bas bruit ou une syndrome inflammatoire aigu. Cependant, certaines protéines circulantes telles que la PLTP (Protéine de Transfert des Phospholipides) permettent de transférer les LPS aux lipoprotéines circulantes dans le sang afin de procéder à leur détoxification.Les objectifs principaux de ces travaux de recherche étaient d’étudier le devenir métabolique de LPS d’origine intestinale ou injectés dans la cavité péritonéale ainsi que l’influence de la PLTP sur ces LPS dans un contexte de maladies inflammatoires et infectieuses telles que l’obésité, le diabète de type 2 (DT2) ou encore une péritonite. Des souris type-sauvage (présence de PLTP endogène active) ont été comparées à des souris génétiquement modifiées déficientes en PLTP après administration de LPS par voie orale ou intrapéritonéale.Au niveau intestinal, la déficience en PLTP est associée à une augmentation de la translocation des LPS de la lumière intestinale vers la circulation, où leur association aux lipoprotéines plasmatique est diminuée en parallèle à un défaut de clairance des lipoprotéines riches en triglycérides (TRL) causé par une diminution de l’activité de la lipoprotéine lipase (LPL), enzyme clé nécessaire à l’hydrolyse des triglycérides. Au niveau de la cavité péritonéale, l’absence de PLTP diminue la liaison des LPS aux lipoprotéines de haute densité (HDL) in situ empêchant ainsi leur inactivation précoce et in fine, leur détoxification par la voie hépatobiliaire.L’absence de PLTP induit ainsi une forte incapacité à détoxifier efficacement les LPS d’origine intestinale et péritonéale, conduisant à une augmentation de la réponse inflammatoire et à de possibles complications plus sévères (obésité, insulinorésistance, syndrome inflammatoire systémique). La PLTP possède donc un rôle majeur dans la neutralisation précoce des LPS dans la cavité abdominale, faisant d’elle une cible thérapeutique intéressante dans le traitement des maladies métaboliques et infectieuses.
... The underlying mechanism of the overweight-EF link may be attributed to chronic lowgrade inflammation. Extensive studies have documented that overweight, especially abdominal adiposity (a marker of visceral fat), can induce systemic low-grade inflammation through activating pro-inflammatory processes in adipose tissue by secreting chemokines and 16:34 in gut microbiota by altering intestinal permeability and releasing endotoxins [35,36]. Inflammation can result in decreased brain volume, reduced white matter integrity, atrophied grey matter, and lower regional blood flow, all of which likely damage EF if occurred in EF-related regions, e.g., frontal, temporal and occipital cortices [7]. ...
Article
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Background While recent works suggested that overweight/obesity may impair executive function (EF), the overweight/obesity-EF relationship has not been well studied in adolescents. Furthermore, no research has investigated adolescent EF impairments across the weight spectrum (e.g., underweight or thinness, normal, overweight/obesity), especially those with underweight condition, with the moderating effect of negative emotions in the weight-EF association being limitedly investigated. We aimed to determine whether overall and abdominal weight spectrum associated with EF impairments and to identity whether negative emotions moderate the weight-EF link in adolescents. Methods We applied a subsample of the SCHEDULE-A project. Adolescents (11–18 years) were recruited using a multi-stage cluster random sampling approach. We measured the overall and abdominal weight spectrum by body mass index z-score and waist-to-height ratio, respectively. We used the Behavior Rating Inventory of Executive Function (BRIEF) to evaluate adolescent EF in nature setting, and utilized the Depression Anxiety and Stress Scales (DASS-21) to assess three types of negative emotional status (i.e., depression, anxiety, and stress). Results Of the 1935 adolescents, 963 (49.8%) were male. We observed that abdominal, not overall, overweight was associated with the Global Executive Composite (GEC) impairment (OR = 1.59, 95% CI 1.07–2.35), particularly for inhibit, emotion control, shift, working memory, and monitor domains. Furthermore, depression moderated the abdominal overweight-GEC association (P = 0.032 for interaction term), especially for emotional control, working memory, and initiate dimensions. Moreover, we also found abdominal thinness was associated with the Metacognition Index problem (OR = 1.33, 95% CI 1.04–1.72), particularly for plan and monitor areas. Conclusions Both abdominal overweight and thinness were associated with adolescent EF, and depression would be a modifiable target to improve EF in adolescents with abdominal overweight. Future longitudinal studies are needed to investigate the causal relationship between abdominal weight spectrum and EF, as well as the underlying mechanisms among adolescents suffering from depression.
... Acetic acid had the highest concentration among VFAs, accounting for about 60%, followed by propionic acid and butyric acid; in addition, acetic acid is a potential precursor of cholesterol and fatty acids, which can be used as a substrate for the de novo synthesis of fatty acids [57]. While propionic acid could participate in gluconeogenesis, and valeric acid and isobutyric acid are the products of bacterial fermentation proteins, marking the catabolism of intestinal proteins [58]. Meanwhile, isobutyric acid could enhance intestinal permeability, which may have a negative impact on intestinal health [59]. ...
Article
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The objective of this study was to evaluate the effects of extruded corn with added amylase under different moisture conditions on the growth performance, intestinal function, and microbiome of weaning piglets. Fourty-eight 24-day-old weaning piglets (Duroc × Landrace × Yorkshire, weaned at 22 ± 1 d) with an initial body weight of 6.76 ± 0.15 kg were randomly assigned to one of four dietary treatments with six replicates per treatment and two pigs per replicate: (1) NL (adding 7.5% water before corn extrusion, negative treatment with low moisture); (2) NH (adding 15.0% water before corn extrusion, negative treatment with high moisture); (3) PL (adding 7.5% water and 4 kg/t α-amylase before corn extrusion, positive treatment with low moisture); and (4) PH (adding 15% water and 4 kg/t α-amylase before corn extrusion, positive treatment with high moisture). Results showed that amylase supplementation (4 vs. 0 kg/t) increased the contents of small molecular oligosaccharides of extruded corn (p < 0.05). Amylase supplementation significantly improved the average daily feed intake, apparent total tract digestibility (ATTD) of dry matter, crude protein, gross energy, crude fat, ash, phosphorus, and calcium, and also increased the activities of jejunal trypsin, α-amylase, lipase, sucrase, maltase, γ-glutamyl transferase and alkaline phosphatase activities, improved the duodenal, jejunal and ileal morphology, and increased the relative mRNA expressions of the ZO-1, OCLN, SGLT1, and GLUT2 genes in the jejunum (p < 0.05), whereas it decreased the contents of isobutyric acid in cecal digesta, as well as acetic acid and isobutyric acid in colonic digesta (p < 0.05). Moreover, the linear discriminant analysis effect size (LEfSe) showed that piglets fed extruded corn with added enzymes contained less intestinal pathogenic bacteria, such as Holdemanella and Desulfovibrio, compared with piglets fed just extruded corn. In summary, the results of the present study indicated that the supplementation of α-amylase during the conditioning and extruding process of corn increased the small molecular oligosaccharide content of corn starch. Moreover, piglets receiving extruded enzyme-added corn had better growth performance, which was associated with the improved intestinal digestive and absorptive function, as well as the intestinal microbiome.
... Saturated fatty acid oxidation supplies the other organ functions, and the beta oxidised fatty acid forms Acetyl Coenzyme-A (Sakamoto et al., 2017). The studies on obesity were focused on excessive and unhealthy food intake and lack of physical activity; however, they also suggested that gut microbiota composition may be linked to other metabolic syndrome diseases, including diabetes mellitus type 2 and hyperlipidemia (Blaut, 2015). ...
Article
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Background: High fat and carbohydrate diets may lead to the malfunction of hepatic cells because of excessive lipolysis of fat tissues and the subsequent increase of free fatty acids in the liver. This is characterised by histological changes in the hepatic cells which then undergo necrosis. High fat and carbohydrate diets may also lead to gut microbiota dysbiosis. Objectives: This study aims to determine the effect of the combination of katuk leaf and black bangle rhizome on the short chain fatty acid (SCFA) profile and liver cell damage in rats induced by a high fat and carbohydrate diet. Methods: The research method used is a preventive experimental study in vivo. Four groups of test animals were distinguished into negative group, positive group, comparative group, and 15% combination test group, which was carried out for 21 days. Examined parameters were: SGPT (Serum Glutamic Pyruvic Transaminase), SGOT (Serum Glutamic Oxaloacetic Transaminase), Triglyceride, and hepatic cells histopathology. The results were examined by SPSS and showed a significant difference (p < 0.05). Results: Parameter results showed the reduction of SGOT in the combination test group. The combination of katuk leaf and black bangle rhizome can increase acetic acid and lower the Manja Roenigk score, and it is possible to inhibit liver cell damage. Conclusion: The combination of katuk leaf (Sauropusxandrogynus L.Merr) and black bangle rhizome (Zingiber ottensii Val) may affect the SCFA levels and help lower the risk of liver cell damage.
... Saturated fatty acid oxidation supplies the other organ functions, and the beta oxidised fatty acid forms Acetyl Coenzyme-A (Sakamoto et al., 2017). The studies on obesity were focused on excessive and unhealthy food intake and lack of physical activity; however, they also suggested that gut microbiota composition may be linked to other metabolic syndrome diseases, including diabetes mellitus type 2 and hyperlipidemia (Blaut, 2015). ...
Article
Full-text available
Background: High fat and carbohydrate diets may lead to the malfunction of hepatic cells because of excessive lipolysis of fat tissues and the subsequent increase of free fatty acids in the liver. This is characterised by histological changes in the hepatic cells which then undergo necrosis. High fat and carbohydrate diets may also lead to gut microbiota dysbiosis. Objectives: This study aims to determine the effect of the combination of katuk leaf and black bangle rhizome on the short chain fatty acid (SCFA) profile and liver cell damage in rats induced by a high fat and carbohydrate diet. Methods: The research method used is a preventive experimental study in vivo. Four groups of test animals were distinguished into negative group, positive group, comparative group, and 15% combination test group, which was carried out for 21 days. Examined parameters were: SGPT (Serum Glutamic Pyruvic Transaminase), SGOT (Serum Glutamic Oxaloacetic Transaminase), Triglyceride, and hepatic cells histopathology. The results were examined by SPSS and showed a significant difference (p < 0.05). Results: Parameter results showed the reduction of SGOT in the combination test group. The combination of katuk leaf and black bangle rhizome can increase acetic acid and lower the Manja Roenigk score, and it is possible to inhibit liver cell damage. Conclusion: The combination of katuk leaf (Sauropusxandrogynus L.Merr) and black bangle rhizome (Zingiber ottensii Val) may affect the SCFA levels and help lower the risk of liver cell damage.
... Another consequence of dysbiosis is the altered production of short-chain fatty acids (SCFA), which depend on various factors in the host microbiota. Butyrate, propionate and acetate represent 90 to 95% of SCFA present in the colon [90,91]. They are produced by fermentation of dietary fibers and are often associated with the prevention of several pathologies linked to inflammation or oxidative stress [92]. ...
Article
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An increasing burden of evidence is pointing toward pesticides as risk factors for chronic disorders such as obesity and type 2 diabetes, leading to metabolic syndrome. Our objective was to assess the impact of chlorpyrifos (CPF) on metabolic and bacteriologic markers. Female rats were exposed before and during gestation and during lactation to CPF (1 mg/kg/day). Outcomes such as weight, glucose and lipid profiles, as well as disturbances in selected gut bacterial levels, were measured in both the dams (at the end of the lactation period) and in their female offspring at early adulthood (60 days of age). The results show that the weight of CPF dams were lower compared to the other groups, accompanied by an imbalance in blood glucose and lipid markers, and selected gut bacteria. Intra-uterine growth retardation, as well as metabolic disturbances and perturbation of selected gut bacteria, were also observed in their offspring, indicating both a direct effect on the dams and an indirect effect of CPF on the female offspring. Co-treatment with inulin (a prebiotic) prevented some of the outcomes of the pesticide. Further investigations could help better understand if those perturbations mimic or potentiate nutritional risk factors for metabolic syndrome through high fat diet.
... The human gut harbours about 100 trillion microbes constituting the human gut microbiota (HGM) [1,2]. The HGM performs a wide variety of functions vital for normal physiology, including the development of the gastrointestinal tract [3], promoting maturation of the immune system [4], pathogen exclusion [5,6], and improving energy capture from dietary components through fermentation [7]. The importance of the HGM in human health has been underpinned by large metagenome sequencing programmes that revealed an enormous catalogue of microbial genes [2,8,9]. ...
Article
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Xylan is one of the major structural components of the plant cell wall. Xylan present in the human diet reaches the large intestine undigested and becomes a substrate to species of the gut microbiota. Here, we characterised the capacity of Limosilactobacillus reuteri and Blautia producta strains to utilise xylan derivatives. We showed that L. reuteri ATCC 53608 and B. producta ATCC 27340 produced β-D-xylosidases, enabling growth on xylooligosaccharide (XOS). The recombinant enzymes were highly active on artificial (p-nitrophenyl β-D-xylopyranoside) and natural (xylobiose, xylotriose, and xylotetraose) substrates, and showed transxylosylation activity and tolerance to xy-lose inhibition. The enzymes belong to glycoside hydrolase family 120 with Asp as nucleophile and Glu as proton donor, as shown by homology modelling and confirmed by site-directed mutagene-sis. In silico analysis revealed that these enzymes were part of a gene cluster in L. reuteri but not in Blautia strains, and quantitative proteomics identified other enzymes and transporters involved in B. producta XOS utilisation. Based on these findings, we proposed a model for an XOS metabolism pathway in L. reuteri and B. producta strains. Together with phylogenetic analyses, the data also revealed the extended xylanolytic potential of the gut microbiota.
... The LPS, derived from pathogenic bacteria in gut dysbiosis, represents a causal link between gut microbiota and lowgrade systemic inflammation (49). Numerous studies have demonstrated that andenterogenic endotoxemia-mediated systemic chronic inflammation aggravates the pathogenesis of AS (50). ...
Article
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Atherosclerosis (AS) is closely associated with abnormally chronic low-grade inflammation and gut dysbiosis. Flaxseed oil (FO) rich in omega-3 polyunsaturated fatty acids (PUFAs), which are mainly composed of alpha-linolenic acid (ALA, 18:3 omega-3), has been demonstrated to exhibit pleiotropic benefits in chronic metabolic diseases. However, the impact of dietary ALA-rich FO on AS and its associated underlying mechanisms remain poorly understood. Thus, the present study was designed as two phases to investigate the effects in atherosclerotic Apolipoprotein E ( ApoE ) −/− mice. In the initial portion, the ApoE −/− mice were randomly allocated to three groups: control group (CON), model group (MOD), and FO-fed model group (MOD/FO) and were treated for 12 weeks. The second phase used antibiotic (AB)-treated ApoE −/− mice were divided into two groups: AB-treated model group (AB/MOD) and FO-fed AB-treated model group (AB/FO). In the results, the dietary ALA-rich FO administration ameliorated atherosclerotic lesion, as well as the parameters of AS (body weights (BWs) and the total bile acids (TBA). Chronic systemic/vascular inflammatory cytokines and in situ macrophages (Mψs) were reduced with FO intervention. In addition, the FO improved the gut integrity and permeability by decreasing the plasma lipopolysaccharide (LPS). Moreover, gut dysbiosis and metabolites [short-chain fatty acids (SCFAs) and bile acids (BAs)] in AS were modulated after FO treatment. Intriguingly, during an AB-treated condition, a significantly weakened amelioration of FO-treated on AS proposed that the intestinal microbiota contributed to the FO effects. A correlation analysis showed close relationships among gut bacteria, metabolites, and inflammation. Collectively, these results suggested that the dietary ALA-rich FO ameliorated the AS in ApoE −/− mice via the gut microbiota-inflammation-artery axis.
... 63 SCFAs are formed primarily in the colon, in which approximately 95% are subsequently absorbed. 64 Butyrate is largely used as the major energy source by colonocytes, while propionate and acetate travel to the liver via the portal vein. In particular, acetate can also reach the peripheral tissues after entering the systemic circulation, inducing a diversity of metabolic and satiety-related effects. ...
Article
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Accumulating evidence indicates that the gut microbiome is an important regulator of body weight, glucose and lipid metabolism, and inflammatory processes, and may thereby play a key role in the aetiology of obesity, insulin resistance and type 2 diabetes. Interindividual responsiveness to specific dietary interventions may be partially determined by differences in baseline gut microbiota composition and functionality between individuals with distinct metabolic phenotypes. However, the relationship between an individual's diet, gut microbiome and host metabolic phenotype is multidirectional and complex, yielding a challenge for practical implementation of targeted dietary guidelines. In this review, we discuss the latest research describing interactions between dietary composition, the gut microbiome and host metabolism. Furthermore, we describe how this knowledge can be integrated to develop precision-based nutritional strategies to improve bodyweight control and metabolic health in humans. Specifically, we will address that (1) insight in the role of the baseline gut microbial and metabolic phenotype in dietary intervention response may provide leads for precision-based nutritional strategies; that (2) the balance between carbohydrate and protein fermentation by the gut microbiota, as well as the site of fermentation in the colon, seems important determinants of host metabolism; and that (3) 'big data', including multiple omics and advanced modelling, are of undeniable importance in predicting (non-)response to dietary interventions. Clearly, detailed metabolic and microbial phenotyping in humans is necessary to better understand the link between diet, the gut microbiome and host metabolism, which is required to develop targeted dietary strategies and guidelines for different subgroups of the population.
... However, it is unknown if a causative link exists between these two parameters. Therefore, it has been postulated that the probiotic strains may provide the additional energy for the host to promote weight gain in sows (47). In another study, Ohigashi et al. (48) reported that the increase in SCFA production is accompanied by a decrease in the luminal pH, which resulted in the suppression of intestinal pathogens and increased nutrient absorption. ...
Article
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The present study determined the effects of different probiotic mixture supplementation to sows from late pregnancy to day 21 postpartum on reproductive performance, colostrum composition, plasma biochemical parameters, and fecal microbiota and metabolites. A total of 80 pregnant sows were randomly assigned to one of four groups (20 sows per group). The sows in the control group (CON group) were fed a basal diet, and those in the BS-A+B, BS-A+BL, and BS-B+BL groups were fed basal diets supplemented with 250 g/t of different probiotic mixture containing either 125 g/t of Bacillus subtilis A (BS-A), Bacillus subtilis B (BS-B), and/or Bacillus licheniformis (BL), respectively. The trial period was from day 85 of pregnancy to day 21 postpartum. The results showed that different dietary probiotic mixture supplementation increased ( P < 0.05) the average weaning weight and average daily gain of piglets, while dietary BS-A+BL supplementation increased the number of weaned piglets ( P < 0.05), litter weight ( P = 0.06), litter weight gain ( P = 0.06), and litter daily gain ( P = 0.06) at weaning compared with the CON group. Different dietary probiotic mixture supplementation improved ( P < 0.05) the colostrum quality by increasing the fat and dry matter concentrations, as well as the protein and urea nitrogen concentrations in the BS-A+BL group. Dietary probiotic mixture BS-B+BL increased the plasma total protein on days 1 and 21 postpartum while decreased the plasma albumin on day 1 postpartum ( P < 0.05). In addition, the plasma high-density lipoprotein-cholesterol was increased in the BS-A+B and BS-B+BL groups on day 21 postpartum, while plasma ammonia was decreased in the BS-A+B and BS-A+BL groups on day 1 and in the three probiotic mixtures groups on day 21 postpartum ( P < 0.05). Dietary supplementation with different probiotic mixture also modified the fecal microbiota composition and metabolic activity in sows during pregnancy and postpartum stages. Collectively, these findings suggest that maternal supplementation with Bacillus subtilis in combination with Bacillus licheniformis are promising strategies for improving the reproductive performance and the overall health indicators in sows, as well as the growth of their offspring.
... The underlying mechanism of the overweight-EF link may be attributed to chronic low-grade in ammation. Extensive studies have documented that overweight, especially abdominal adiposity (a marker of visceral fat), can induce systemic low-grade in ammation through activating pro-in ammatory processes in adipose tissue by secreting chemokines and in gut microbiota by altering intestinal permeability and releasing endotoxins [28,29]. In ammation can result in decreased brain volume, reduced white matter integrity, atrophied grey matter, and lower regional blood ow, all of which likely damage EF if occurred in EF-related regions, e.g., frontal, temporal and occipital cortices [30]. ...
Preprint
Full-text available
Background: Overweight/obesity may impair executive function (EF). However, adolescent EF impairments across the weight spectrum were not well studied, with the moderating effect of negative emotions in the weight-EF association being limitedly investigated. We aimed to determine whether overall and abdominal weight spectrum associated with EF impairments and to identity whether negative emotions moderate the weight-EF link in adolescents. Methods: We applied a subsample of the SCHEDULE-A project. Adolescents (11-18 years) were recruited using a multi-stage cluster random sampling approach. Overall and abdominal weight were measured by body mass index z-score and waist-to-height ratio, respectively. We used the Behavior Rating Inventory of Executive Function (BRIEF) to evaluate adolescent EF in nature setting, and utilized the Depression Anxiety and Stress Scales (DASS-21) to assess three types of negative emotional states (i.e., depression, anxiety, and stress). Results: Of the 1 935 adolescents, 963 (49.8%) were male. We observed that abdominal, not overall, overweight was associated with the Global Executive Composite (GEC) impairment (OR = 1.59, 95% CI: 1.07-2.35), particularly for inhibit, emotion control, shift, working memory, and monitor domains. Furthermore, depression moderated the abdominal overweight-GEC association (P = 0.032 for interaction term), especially for emotional control, working memory, and initiate dimensions. Moreover, we also found abdominal thinness was associated with the Metacognition Index problem (OR = 1.33, 95% CI: 1.04-1.72), particularly for plan and monitor areas. Conclusions: Both abdominal overweight and thinness were associated with adolescent EF, and depression would be a modifiable target to improve EF in adolescents with abdominal overweight.
... BA could also be utilized as energy in host gut tissues for the tissue growth, so as to ensure the integrity of intestinal epithelial structure. Furthermore, BA influences gene expression by inhibiting histone deacetylase, which is related to the arrest and activation of apoptosis (Blaut, 2015). In addition to directly acting on the colon, SCFA can also participate in the immune response to exert anti-inflammatory effect. ...
Article
Inflammatory bowel disease afflicted individuals and most medications have adverse effects. The objection of this study is to investigate whether the major yolk protein (MYP) could aid in the remission of colitis. The function of MYP on acute colitis was assessed through a dextran sulfate sodium -induced colitis mice model. Compared to the model group, the anti-inflammatory cytokines increased significantly in the MYP group, whereas the pro-inflammatory cytokines were not significantly different between the model and treatment group. The results also showed that supplementation of MYP improved the shift in microbial community composition of mice with colitis induced by DSS. In addition, MYP supplementation enriched the contents of fecal short-chain fatty acids. The alleviation of MYP on the colitis was probably related to repair the dysbiosis state of colonic microbiota, which thus induced an increase in short-chain fatty acids level and secrete anti-inflammatory cytokines (IL-4 and IL-10). In sum, oral MYP may be a potential candidate for the attenuating of acute colitis.
... A number of SCFA producers which belong to the family Ruminococcaceae, including Ruminiclostridium_5, Ruminococcaceae_UCG-014, and [Ruminococcus]_torques_group, were significantly enriched in the cecum. These bacteria are considered as dominant players in the degradation of diverse polysaccharides and fibers (59,60). ...
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The gut microbiota of chickens plays an important role in host physiology. However, the colonization and prevalence of gut microbiota have not been well-characterized. Here, we performed 16S rRNA gene sequencing on the duodenal, cecal and fecal microbiota of broilers at 1, 7, 21, and 35 days of age and characterized the dynamic succession of microbiota across the intestinal tract. Our results showed that Firmicutes was the most abundant phylum detected in each gut site at various ages, while the microbial diversity and composition varied among the duodenum, cecum, and feces at different ages. The microbial diversity and complexity of the cecal microbiota increased with age, gradually achieving stability at 21 days of age. As a specific genus in the cecum, Clostridium_sensu_stricto_1 accounted for 83.50% of the total abundance at 1 day of age, but its relative abundance diminished with age. Regarding the feces, the highest alpha diversity was observed at 1 day of age, significantly separated from the alpha diversity of other ages. In addition, no significant differences were observed in the alpha diversity of duodenal samples among 7, 21, and 35 days of age. The predominant bacterium, Lactobacillus , was relatively low (0.68–6.04%) in the intestinal tract of 1-day-old chicks, whereas its abundance increased substantially at 7 days of age and was higher in the duodenum and feces. Escherichia-Shigella , another predominant bacterium in the chicken intestinal tract, was also found to be highly abundant in fecal samples, and the age-associated dynamic trend coincided with that of Lactobacillus . In addition, several genera, including Blautia, Ruminiclostridium_5, Ruminococcaceae_UCG-014 , and [Ruminococcus]_torques_group , which are related to the production of short-chain fatty acids, were identified as biomarker bacteria of the cecum after 21 days of age. These findings shed direct light on the temporal and spatial dynamics of intestinal microbiota and provide new opportunities for the improvement of poultry health and production.
... Alternatively, Pedersen et al. presented that the altered composition of gut microbiota impacts the complete catabolism of BCAAs and insulin resistance, thus highlighting the independent contribution to the elevation of BCAAs [85]. Lipopolysaccharide (LPS) is the outer coat of Gram-negative species of the gut microbiota, and is known to increase intestinal permeability and is suggested by some studies to trigger inflammation and further aggravate IR and T2DM [77,86]. On the contrary, lipopolysaccharide-binding protein (LBP) that binds to LPS in a BCAA-enriched mixture (BCAAem) displayed a significant reduction in LPS levels (p < 0.05) [87,88]. ...
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Amino acids are needed for general bodily function and well-being. Despite their importance, augmentation in their serum concentration is closely related to metabolic disorder, insulin resistance (IR), or worse, diabetes mellitus. Essential amino acids such as the branched-chain amino acids (BCAAs) have been heavily studied as a plausible biomarker or even a cause of IR. Although there is a long list of benefits, in subjects with abnormal amino acids profiles, some amino acids are correlated with a higher risk of IR. Metabolic dysfunction, upregulation of the mammalian target of the rapamycin (mTOR) pathway, the gut microbiome, 3-hydroxyisobutyrate, inflammation, and the collusion of G-protein coupled receptors (GPCRs) are among the indicators and causes of metabolic disorders generating from amino acids that contribute to IR and the onset of type 2 diabetes mellitus (T2DM). This review summarizes the current understanding of the true involvement of amino acids with IR. Additionally, the involvement of GPCRs in IR will be further discussed in this review.
... Finally, the third mechanism is associated with the regulation of the levels of LPS of bacterial origin into the plasma, which can induce chronic subclinical inflammation. The last one leads to the development of insulin resistance through the activation of TLCR [40,41]. ...
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Gut microbiota is a group of microorganisms that are deposited throughout the entire gastrointestinal tract. Currently, thanks to genomic tools, studies of gut microbiota have pointed towards the understanding of the metabolism of important bacteria that are not cultivable and their relationship with human homeostasis. Alterations in the composition of gut microbiota could explain, at least in part, some epidemics, such as diabetes and obesity. Likewise, dysbiosis has been associated with gastrointestinal disorders, neurodegenerative diseases, and even cancer. That is why several studies have recently been focused on the direct relationship that these types of conditions have with the specific composition of gut microbiota, as in the case of the microbiota–intestine–brain axis. In the same way, the control of microbiota is related to the diet. Therefore, this review highlights the importance of gut microbiota, from its composition to its relationship with the human health–disease condition, as well as emphasizes the effect of probiotic and prebiotic consumption on the balance of its composition.
... Butyrate was proposed to stimulate the release of GLP-1 from intestinal L-cells (59), while acetate and propionate both actively participate in lipid and glucose metabolism (60). We provide further evidence to support the view that loss of Clostridia of Firmicutes was recently found as one of key features associated with obesity, and Clostridia treatment has been applied to control lipid absorption and reduce adiposity (61). ...
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Background: Vertical sleeve gastrectomy (VSG) is becoming a prioritized surgical intervention for obese individuals; however, the brain circuits that mediate its effective control of food intake and predict surgical outcome remain largely unclear. Methods: In this observational cohort study, 80 patients with obesity were screened. 36 patients together with 26 normal-weight subjects were enrolled and evaluated using the 21-item Three-Factor Eating Questionnaire (TFEQ), MRI scanning, plasma intestinal hormone analysis and fecal sample sequencing. 32 cases underwent VSG treatment and 19 subjects completed an average of four-month follow-up evaluation. Data-driven regional homogeneity (ReHo) coupled with seed-based connectivity analysis were used to quantify VSG-related brain activity. Longitudinal alterations of body weight, eating behavior, brain activity, gastrointestinal hormones and gut microbiota were detected and subjected to repeated measures correlation analysis. Results: VSG induced significant functional changes in the right putamen (PUT.R) and left supplementary motor area, both of which correlated with weight loss and TFEQ scores. Moreover, postprandial levels of active glucagon-like peptide-1 (aGLP-1) and Ghrelin were associated with ReHo of PUT.R; meanwhile, relative abundance of Clostridia increased by VSG was associated with improvements in aGLP-1 secretion, PUT.R activity and weight loss. Importantly, VSG normalized excessive functional connectivities with PUT.R, among which baseline connectivity between PUT.R and right orbitofrontal cortex was related to postoperative weight loss. Conclusions: VSG causes correlated alterations of gut-brain axis, including Clostridia, postprandial aGLP-1, PUT.R activity and eating habits. Preoperative connectivity of PUT.R may represent a potential predictive marker of surgical outcome in patients with obesity.
... Bacteria in the cecum and colon have the enzymatic machinery to ferment dietary fibre into short-chain fatty acids (SCFAs), mainly acetate, butyrate, and propionate at a ratio 3:1:1 which are absorbed into systemic circulation. Binding of these fatty acids to G-protein-coupled receptors (GPCRs) in various tissues is thought to mediate the metabolic effects of fibre intake [21,25,87,88]. Butyrate, acetate, and propionate bind, with the highest selectivity, to the G-protein coupled receptors GPR109A, GPR43 and GPR41, respectively [87][88][89]. ...
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Obesity caused by the overconsumption of calories has increased to epidemic proportions. Insulin resistance is often associated with an increased adiposity and is a precipitating factor in the development of cardiovascular disease, type 2 diabetes, and altered metabolic health. Of the various factors contributing to metabolic impairments, nutrition is the major modifiable factor that can be targeted to counter the rising prevalence of obesity and metabolic diseases. However, the macronutrient composition of a nutritionally balanced “healthy diet” are unclear, and so far, no tested dietary intervention has been successful in achieving long-term compliance and reductions in body weight and associated beneficial health outcomes. In the current review, we briefly describe the role of the three major macronutrients, carbohydrates, fats, and proteins, and their role in metabolic health, and provide mechanistic insights. We also discuss how an integrated multi-dimensional approach to nutritional science could help in reconciling apparently conflicting findings.
... Depending on the diet and the type of SCFA produced, different metabolic pathways are triggered through different receptors. SCFAs modulate host lipids and glucose metabolism through the GPR41 and GPR43 receptor junctions [102]. Although these receptors show over 40% structural similarity, they differ in their ligand binding specificity [103]. ...
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Short-chain fatty acids (SCFAs), as products of intestinal bacterial metabolism, are particularly relevant in the diagnosis of intestinal dysbiosis. The most common studies of microbiome metabolites include butyric acid, propionic acid and acetic acid, which occur in varying proportions depending on diet, age, coexisting disease and other factors. During pregnancy, metabolic changes related to the protection of energy homeostasis are of fundamental importance for the developing fetus, its future metabolic fate and the mother’s health. SCFAs act as signaling molecules that regulate the body’s energy balance through G-protein receptors. GPR41 receptors affect metabolism through the microflora, while GPR43 receptors are recognized as a molecular link between diet, microflora, gastrointestinal tract, immunity and the inflammatory response. The possible mechanism by which the gut microflora may contribute to fat storage, as well as the occurrence of gestational insulin resistance, is blocking the expression of the fasting-induced adipose factor. SCFAs, in particular propionic acid via GPR, determine the development and metabolic programming of the fetus in pregnant women. The mechanisms regulating lipid metabolism during pregnancy are similar to those found in obese people and those with impaired microbiome and its metabolites. The implications of SCFAs and metabolic disorders during pregnancy are therefore critical to maternal health and neonatal development. In this review paper, we summarize the current knowledge about SCFAs, their potential impact and possible mechanisms of action in relation to maternal metabolism during pregnancy. Therefore, they constitute a contemporary challenge to practical nutritional therapy. Material and methods: The PubMed database were searched for “pregnancy”, “lipids”, “SCFA” in conjunction with “diabetes”, “hypertension”, and “microbiota”, and searches were limited to work published for a period not exceeding 20 years in the past. Out of 2927 publication items, 2778 papers were excluded from the analysis, due to being unrelated to the main topic, conference summaries and/or articles written in a language other than English, while the remaining 126 publications were included in the analysis.
... Additionally, Ruminococcus_torques_group, categorized as Clostridium cluster XIVa, mainly produces butyrate (45). Butyrate-producing bacteria were found to promote fat deposition (46) because they are able to convert dietary fiber to butyrate by fermentation to provide additional energy to the host (26). In our study, the ducks with high Ruminococcus_torques_group abundance showed significantly higher AFW (P < 0.05) and a tendency toward higher AFP (P < 0.01) than the ducks with low Ruminococcus_torques_group abundance ( Figure 7B). ...
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Ducks with the same genetic background vary greatly in their adiposity phenotypes. The gut microbiota plays an essential role in host physiological development and metabolism including fat deposition. However, the association of the gut microbiota with the lipogenic phenotype of ducks remains unknown. In this study, we investigated the cecal microbiota of adult Muscovy ducks and the correlation of the cecal microbiota with fat phenotypes. A total of 200 Muscovy ducks were selected from a population of 5,000 Muscovy ducks to record their abdominal fat weight and collect their cecal contents after being slaughtered and defeathered. The cecal contents were subjective to DNA isolation and 16S rRNA gene sequencing. The results were sorted according to the percentage of abdominal fat and the top 20% (n = 40) and the bottom 20% (n = 40) were set as the high and low groups, respectively. Our results indicated that in the cecum of Muscovy ducks, Bacteroidetes, Firmicutes, and Fusobacteria were the predominant phyla while Bacteroides, Oscillospiraceae_uncultured, Parabacteroides, and Bacteroidales_norank were the top 4 dominant genera. Abdominal fat weight (18.57~138.10 g) and percentage of abdominal fat (1.02~27.12%) were significantly correlated (R2 = 0.92, P < 0.001). Although the lipogenic phenotypes of ducks had a significant difference (P < 0.05), the α-diversities of the high and low groups were not significantly different (P > 0.05). Nevertheless, after random forest analysis, we identified two genera, Treponema and Ruminococcus_torques_group, that were significantly associated with fat deposition in Muscovy ducks. In addition, the abundances of Treponema and Ruminococcus_torques_group gave a significantly negative and positive association with abdominal fat weight, respectively (P < 0.05). Ducks with a low level of Treponema exhibited a tendency toward a high percentage of abdominal fat (P < 0.01), while the percentage of abdominal fat in ducks with high Ruminococcus_torques_group abundance tended to be higher than that in ducks with low Ruminococcus_torques_group abundance (P < 0.01). These findings could provide the basic data on the cecal microbiota in Muscovy ducks as well as a theoretical foundation to limit the fat deposition by modulating the gut microbiota in the duck industry.
... The present study showed that the main SCFAs in jejunal and ileal contents were acetate and butyrate; while those in colonic contents were acetate, propionate, and butyrate. Acetate was considered to be preferentially used for energy generation and lipogenesis in all kinds of tissues [32]. Butyrate increases energy expenditure and prevents diet-induced obesity and insulin resistance [9,33]. ...
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Background Gut microbiota and their metabolites were associated with obesity. Our previous study showed that maternal body fat percentage increased from days 45 to 110 of gestation in a Huanjiang mini-pig model. Thus, 16S rRNA sequencing and metabonomic techniques were used to investigate the changes of maternal gut microbiota composition and microbial metabolite profile from days 45 to 110 of gestation. Results The abundances of Clostridium_sensu_stricto_1, Romboutsia, Turicibacter, and Streptococcus in jejunum contents were higher in day 110 than those in day 45 or 75 of gestation. In ileum, the abundance of Streptococcus was the highest (P < 0.05) at day 110 of gestation, as well as the metabolism function of jejunal and ileal microbiota. The ileal butyrate and acetate concentrations were the highest at day 45 and day 110 of gestation, respectively. In colon, the concentrations of cadaverine and spermine were the highest (P < 0.05) at days 45 and 110 of gestation, respectively. Metabonomic analysis demonstrated that metabolic pathways including glutamine and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and alanine, aspartate, and glutamate metabolism changed during gestation. Conclusions Microbiota composition and metabolites changed dramatically from the early to the late pregnancy, which might be associated with the maternal fat accumulation.
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Traditional Chinese medicine polysaccharides is a biologically active ingredient that is not easy to be digested. It is fermented by intestinal microflora to promote qualitative and selective changes in the composition of the intestinal microbiome, which often result in beneficial effects on the health of the host. People call it “prebiotics”. In this review, we systematically summarized the anti-diabetic effect of traditional Chinese medicine polysaccharides. These polysaccharides regulate the metabolism of sugar and lipids by inter-influence with the intestinal microflora, and maintain human health, while improving type 2 diabetes-like symptoms such as high blood glucose, and abnormal glucose and lipid metabolism.
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To truly eliminate the possibility of diabetic foot ulcers, the elimination of the symptoms of diabetes is essential. There are many forms of diabetes and there is no one diet that is effective for all patients. It is essential that a proper diet is utilized and for most diabetic patients a reduction in weight and the restoration of a properly balanced microbiota can eliminate the devastating effects of diabetes including foot ulcers. This review examines in detail the different types of diets, and how they affect the host and the microbiota to eliminate as much as possible the risk of foot ulcers. Microbiota, diet, incretins, and insulin all directly affect the deposition of fats which causes insulin insensitivity and diabetes in most patients.
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Background: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that imposes a huge economic burden on global public health. And the gut-liver axis theory supports the therapeutic role of intestinal flora in the development and progression of NAFLD. To this end, we designed bioinformatics study on the relationship between intestinal flora disorder and NAFLD, to explore the possible molecular mechanism of intestinal flora interfering with NAFLD. Methods: Differentially expressed genes for NAFLD were obtained from the GEO database. And the disease genes for NAFLD and intestinal flora disorder were obtained from the disease databases. The protein-protein interaction network was established by string 11.0 database and visualized by Cytoscape 3.7.2 software. Cytoscape plug-in MCODE and cytoHubba were used to screen the potential genes of intestinal flora disorder and NAFLD, to obtain potential targets for intestinal flora to interfere in the occurrence and process of NAFLD. Enrichment analysis of potential targets was carried out using R 4.0.2 software. Results: The results showed that 7 targets might be the key genes for intestinal flora to interfere with NAFLD. CCL2, IL6, IL1B, and FOS are mainly related to the occurrence and development mechanism of NAFLD, while PTGS2, SPINK1, and C5AR1 are mainly related to the intervention of intestinal flora in the occurrence and development of NAFLD. The gene function is mainly reflected in basic biological processes, including the regulation of metabolic process, epithelial development, and immune influence. The pathway is mainly related to signal transduction, immune regulation, and physiological metabolism. The TNF signaling pathway, AGE-RAGE signaling pathway in diabetic activity, and NF-Kappa B signaling pathways are important pathways for intestinal flora to interfere with NAFLD. According to the analysis results, there is a certain correlation between intestinal flora disorder and NAFLD. Conclusion: It is speculated that the mechanism by which intestinal flora may interfere with the occurrence and development of NAFLD is mainly related to inflammatory response and insulin resistance. Nevertheless, further research is needed to explore the specific molecular mechanisms.
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Gut microbiota is a microecosystem composed of various microorganisms. It plays an important role in human metabolism, and its metabolites affect different tissues and organs. Intestinal flora maintains the intestinal mucosal barrier and interacts with the immune system. The liver is closely linked to the intestine by the gut-liver axis. As the first organ that comes into contact with blood from the intestine, the liver will be deeply influenced by the gut microbiota and its metabolites, and the intestinal leakage and the imbalance of the flora are the trigger of the pathological reaction of the liver. In this paper, we discuss the role of gut microbiota and its metabolites in the pathogenesis and development of autoimmune liver diseases((including autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), metabolic liver disease such as non-alcoholic fatty liver disease, cirrhosisits and its complications, and liver cancer from the perspective of immune mechanism. And the recent progress in the treatment of these diseases was reviewed from the perspective of gut microbiota.
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Gut microbiota (GM) is a micro-ecosystem composed of all microorganisms in the human intestine. The interaction between GM and the host plays an important role in maintaining normal physiological functions in the host. Dysbiosis of the GM may cause various diseases. GM has been demonstrated to be associated with human health and disease, and changes during individual development and disease. Pregnancy is a complicated physiological process. Hormones, the immune system, metabolism, and GM undergo drastic changes during pregnancy. Gastrointestinal diseases during pregnancy, such as hepatitis, intrahepatic cholestasis of pregnancy, and pre-eclampsia, can affect both maternal and fetal health. The dysregulation of GM during pregnancy may lead to a variety of diseases, including gastrointestinal diseases. Herein, we review recent research articles on GM in pregnancy-related gastrointestinal diseases, discuss the interaction of the GM with the host under normal physiological conditions, gastrointestinal diseases, and pregnancy-specific disorders. As more attention is paid to reproductive health, the pathogenic mechanism of GM in gastrointestinal diseases during pregnancy will be further studied to provide a theoretical basis for the use of probiotics to treat these diseases.
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Type 2 diabetes mellitus (T2DM) may lead to abnormally elevated blood glucose, lipid metabolism disorder, and low-grade inflammation. Besides, the development of T2DM is always accompanied by gut microbiota dysbiosis and metabolic dysfunction. In this study, the T2DM mice model was established by feeding a high-fat/sucrose diet combined with injecting a low dose of streptozotocin. Additionally, the effects of oral administration of ethanol extract from Sanghuangporous vaninii (SVE) on T2DM and its complications (including hypoglycemia, hyperlipidemia, inflammation, and gut microbiota dysbiosis) were investigated. The results showed SVE could improve body weight, glycolipid metabolism, and inflammation-related parameters. Besides, SVE intervention effectively ameliorated the diabetes-induced pancreas and jejunum injury. Furthermore, SVE intervention significantly increased the relative abundances of Akkermansia, Dubosiella, Bacteroides, and Parabacteroides, and decreased the levels of Lactobacillus, Flavonifractor, Odoribacter, and Desulfovibrio compared to the model group (LDA > 3.0, p < 0.05). Metabolic function prediction of the intestinal microbiota by PICRUSt revealed that glycerolipid metabolism, insulin signaling pathway, PI3K-Akt signaling pathway, and fatty acid degradation were enriched in the diabetic mice treated with SVE. Moreover, the integrative analysis indicated that the key intestinal microbial phylotypes in response to SVE intervention were strongly correlated with glucose and lipid metabolism-associated biochemical parameters. These findings demonstrated that SVE has the potential to alleviate T2DM and its complications by modulating the gut microbiota imbalance.
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Malnutrition continues to threaten the lives of millions across the world, with children being hardest hit. Although inadequate access to food and infectious disease are the primary causes of childhood malnutrition, the gut microbiota may also contribute. This review considers the evidence on the role of diet in modifying the gut microbiota, and how the microbiota impacts childhood malnutrition. It is widely understood that the gut microbiota of children is influenced by diet, which, in turn, can impact child nutritional status. Additionally, diarrhoea, a major contributor to malnutrition, is induced by pathogenic elements of the gut microbiota. Diarrhoea leads to malabsorption of essential nutrients and reduced energy availability resulting in weight loss, which can lead to malnutrition. Alterations in gut microbiota of severe acute malnourished (SAM) children include increased Proteobacteria and decreased Bacteroides levels. Additionally, the gut microbiota of SAM children exhibits lower relative diversity compared with healthy children. Thus, the data indicate a link between gut microbiota and malnutrition in children, suggesting that treatment of childhood malnutrition should include measures that support a healthy gut microbiota. This could be of particular relevance in sub-Saharan Africa and Asia where prevalence of malnutrition remains a major threat to the lives of millions.
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Along with the brief outline of the definition evolution of dietary fibers, this chapter focuses on how the physical and chemical structures of fibers are related to the health effects. The role of fiber in the human digestive tract including oral, gastric, small intestinal, and large intestinal phases is also discussed. Our further emphasis is on the colonic microbial fermentation performance and health implications of dietary fibers. Fibers with higher water holding capacity or viscosity are desirable for slowing down the metabolic response (e.g., post prandial blood glucose level), whereas the fibers with slow fermentation throughout the colon and higher level of butyrate/propionate production are considered ideal for colonic health. Thus foods that have the balance of viscous and slowly fermentable fibers are considered beneficial in terms of overall nutrition and health. Although role of fibers in small intestine is well studied and known, how the fiber specificity can modulate the gut microbial ecology for desired health benefits still needs further research investigation.
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The study aimed to evaluate the metabolism and resistance to the gastrointestinal tract conditions of Bacillus pumilus UAMX (BP-UAMX) isolated from overweight individuals using genomic tools. Specifically, we assessed its ability to metabolize various carbon sources, its resistance to low pH exposure, and its growth in the presence of bile salts. The genomic and bioinformatic analyses included the prediction of gene and protein metabolic functions, a pan-genome and phylogenomic analysis. BP-UAMX survived at pH 3, while bile salts (0.2–0.3% w/v) increased its growth rate. Moreover, it showed the ability to metabolize simple and complex carbon sources (glucose, starch, carboxymethyl-cellulose, inulin, and tributyrin), showing a differentiated electrophoretic profile. Genome was assembled into a single contig, with a high percentage of genes and proteins associated with the metabolism of amino acids, carbohydrates, and lipids. Antibiotic resistance genes were detected, but only one beta-Lactam resistance protein related to the inhibition of peptidoglycan biosynthesis was identified. The pan-genome of BP-UAMX is still open with phylogenetic similarities with other Bacillus of human origin. Therefore, BP-UAMX seems to be adapted to the intestinal environment, with physiological and genomic analyses demonstrating the ability to metabolize complex carbon sources, the strain has an open pan-genome with continuous evolution and adaptation.
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Growing evidence highlights the crucial role of gut microbiota in affecting different aspects of obesity. Considering the ability of deep transcranial magnetic stimulation (dTMS) to modulate the cortical excitability, the reward system, and, indirectly, the autonomic nervous system (ANS), we hypothesized a potential role of dTMS in affecting the brain-gut communication pathways, and the gut microbiota composition in obesity. In a hospital setting, 22 subjects with obesity (5 M, 17 F; 44.9 ± 2.2 years; BMI 37.5 ± 1.0 kg/m2) were randomized into three groups receiving 15 sessions (3 per week for 5 weeks) of high frequency (HF), low frequency (LF) dTMS, or sham stimulation. Fecal samples were collected at baseline and after 5 weeks of treatment. Total bacterial DNA was extracted from fecal samples using the QIAamp DNA Stool Mini Kit (Qiagen, Italy) and analyzed by a metagenomics approach (Ion Torrent Personal Genome Machine). After 5 weeks, a significant weight loss was found in HF (HF: −4.1 ± 0.8%, LF: −1.9 ± 0.8%, sham: −1.3 ± 0.6%, p = 0.042) compared to LF and sham groups, associated with a decrease in norepinephrine compared to baseline (HF: −61.5 ± 15.2%, p < 0.01; LF: −31.8 ± 17.1%, p < 0.05; sham: −35.8 ± 21.0%, p > 0.05). Furthermore, an increase in Faecalibacterium (+154.3% vs. baseline, p < 0.05) and Alistipes (+153.4% vs. baseline, p < 0.05) genera, and a significant decrease in Lactobacillus (−77.1% vs. baseline, p < 0.05) were found in HF. Faecalibacterium variations were not significant compared to baseline in the other two groups (LF: +106.6%, sham: +27.6%; p > 0.05) as well as Alistipes (LF: −54.9%, sham: −15.1%; p > 0.05) and Lactobacillus (LF: −26.0%, sham: +228.3%; p > 0.05) variations. Norepinephrine change significantly correlated with Bacteroides (r2 = 0.734; p < 0.05), Eubacterium (r2 = 0.734; p < 0.05), and Parasutterella (r2 = 0.618; p < 0.05) abundance variations in HF. In conclusion, HF dTMS treatment revealed to be effective in modulating gut microbiota composition in subjects with obesity, reversing obesity-associated microbiota variations, and promoting bacterial species representative of healthy subjects with anti-inflammatory properties.
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Epigallocatechin-3-gallate (EGCG) and caffeine constitute the most effective ingredients of weight loss in tea. However, whether combination of EGCG and caffeine exhibits anti-obesity synergy remains unclear. Here, we showed low-doses of EGCG and caffeine used in combination led to synergistic anti-obesity effects equivalent to those of high-dose EGCG. Furthermore, combination treatment exhibited a synergistic effect on altering gut microbiota, including decreased Firmicutes level and increased Bifidobacterium level. Other notable effects of combination treatment included synergistic effects on: increasing fecal acetic acid, propionic acid, and total SCFAs; decreasing expression of GPR43; and increasing microbial bile salt hydrolase gene copies in the gut, facilitating generation of unconjugated BAs and enhancing fecal BA loss. Additionally, combination treatment demonstrated synergistic effects toward increasing the expression of hepatic TGR5 and decreasing the expression of intestinal FXR-FGF15, resulting in increased expression of hepatic CYP7A1. Thus, the synergistic effect may be attributed to regulation of gut microbiota and BA metabolism.
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Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, respectively, on a nutritional basis and that a 4-week high-fat diet chronically increased plasma LPS concentration two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly , a high-fat diet increased the proportion of an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat–fed mice. In addition, adipose tissue F4/80-positive cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet–induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.
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Unlabelled: The intestines of obese humans and mice are enriched with Erysipelotrichi, a class within the Firmicutes. Clostridium ramosum, a member of the Erysipelotrichi, is associated with symptoms of the metabolic syndrome in humans. To clarify the possible obesogenic potential of this bacterial species and to unravel the underlying mechanism, we investigated the role of C. ramosum in obesity development in gnotobiotic mice. Mice were associated with a simplified human intestinal (SIHUMI) microbiota of eight bacterial species, including C. ramosum, with the SIHUMI microbiota except C. ramosum (SIHUMIw/oCra), or with C. ramosum only (Cra) and fed a high-fat diet (HFD) or a low-fat diet (LFD). Parameters related to the development of obesity and metabolic diseases were compared. After 4 weeks of HFD feeding, the mouse groups did not differ in energy intake, diet digestibility, gut permeability, and parameters of low-grade inflammation. However, SIHUMI and Cra mice fed the HFD gained significantly more body weight and body fat and displayed higher food efficiency than SIHUMIw/oCra mice fed the HFD. Gene expression of glucose transporter 2 (Glut2) in jejunal mucosa and of fatty acid translocase (CD36) in ileal mucosa was significantly increased in the obese SIHUMI and Cra mice compared with the less obese SIHUMIw/oCra mice. The data demonstrate that the presence of C. ramosum in SIHUMI and Cra mice enhanced diet-induced obesity. Upregulation of small intestinal glucose and fat transporters in these animals may contribute to their increased body fat deposition. Importance: Obesity is a growing health problem worldwide. Changes in the proportions of Bacteroidetes and Firmicutes, the two dominant phyla in the human and the murine intestinal tract, link the intestinal microbiota to obesity. Erysipelotrichi, a class within the Firmicutes, increase in response to high-fat feeding in mice. Clostridium ramosum, a member of the Erysipelotrichi, has been linked to symptoms of the metabolic syndrome. We hypothesized that C. ramosum promotes obesity development and related pathologies. Our experiments in gnotobiotic mice show that C. ramosum promoted diet-induced obesity, probably by enhancing nutrient absorption. Identification of obesogenic bacteria and understanding their mode of action enable the development of novel strategies for the treatment of this epidemic disease. Pharmaceuticals that target obesogenic bacteria or their metabolism could help to prevent and treat obesity and related disorders in the future.
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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.
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Mutations in the WNT/beta-catenin pathway are responsible for initiating the majority of colorectal cancers (CRCs). We have previously shown that hyperactivation of this signaling by histone deacetylase inhibitors (HDACis) such as butyrate, a fermentation product of dietary fiber, promotes CRC cell apoptosis. The extent of association between beta-catenin and the transcriptional coactivator CREB-binding protein (CBP) influences WNT/catenin signaling and, therefore, colonic cell physiology. CBP functions as a histone acetylase (HAT); therefore, we hypothesized that the modulation of WNT/catenin activity by CBP modifies the ability of the HDACi butyrate to hyperinduce WNT signaling and apoptosis in CRC cells. Our findings indicate that CBP affects the hyperinduction of WNT activity by butyrate. ICG-001, which specifically blocks association between CBP and beta-catenin, abrogates the butyrate-triggered increase in the number of CRC cells with high levels of WNT/catenin signaling. Combination treatment of CRC cells with ICG-001 and butyrate results in cell type-specific effects on apoptosis. Further, both butyrate and ICG-001 repress CRC cell proliferation, with additive effects in suppressing cell growth. Our study strongly suggests that ICG-001-like agents would be effective against butyrate/HDACi-resistant CRC cells. Therefore, ICG-001-like agents may represent an important therapeutic option for CRCs that exhibit low-fold hyperactivation of WNT activity and apoptosis in the presence of HDACis. The findings generated from this study may lead to approaches that utilize modulation of CBP activity to facilitate CRC therapeutic or chemopreventive strategies.
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The distal human intestine harbors trillions of microbes that allow us to extract calories from otherwise indigestible dietary polysaccharides. The products of polysaccharide fermentation include short-chain fatty acids that are ligands for Gpr41, a G protein-coupled receptor expressed by a subset of enteroendocrine cells in the gut epithelium. To examine the contribution of Gpr41 to energy balance, we compared Gpr41−/− and Gpr41+/+ mice that were either conventionally-raised with a complete gut microbiota or were reared germ-free and then cocolonized as young adults with two prominent members of the human distal gut microbial community: the saccharolytic bacterium, Bacteroides thetaiotaomicron and the methanogenic archaeon, Methanobrevibacter smithii. Both conventionally-raised and gnotobiotic Gpr41−/− mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (+/+) littermates, despite similar levels of chow consumption. These differences are not evident when germ-free WT and germ-free Gpr41 knockout animals are compared. Functional genomic, biochemical, and physiologic studies of germ-free and cocolonized Gpr41−/− and +/+ littermates disclosed that Gpr41-deficiency is associated with reduced expression of PYY, an enteroendocrine cell-derived hormone that normally inhibits gut motility, increased intestinal transit rate, and reduced harvest of energy (short-chain fatty acids) from the diet. These results reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota. • host-microbial interactions • energy balance • enteroendocrine cells • nutrient sensing • polysaccharide fermentation
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Evidence for the occurrence of microbial breakdown of carbohydrate in the human colon has been sought by measuring short chain fatty acid (SCFA) concentrations in the contents of all regions of the large intestine and in portal, hepatic and peripheral venous blood obtained at autopsy of sudden death victims within four hours of death. Total SCFA concentration (mmol/kg) was low in the terminal ileum at 13 +/- 6 but high in all regions of the colon ranging from 131 +/- 9 in the caecum to 80 +/- 11 in the descending colon. The presence of branched chain fatty acids was also noted. A significant trend from high to low concentrations was found on passing distally from caecum to descending colon. pH also changed with region from 5.6 +/- 0.2 in the caecum to 6.6 +/- 0.1 in the descending colon. pH and SCFA concentrations were inversely related. Total SCFA (mumol/l) in blood was, portal 375 +/- 70, hepatic 148 +/- 42 and peripheral 79 +/- 22. In all samples acetate was the principal anion but molar ratios of the three principal SCFA changed on going from colonic contents to portal blood to hepatic vein indicating greater uptake of butyrate by the colonic epithelium and propionate by the liver. These data indicate that substantial carbohydrate, and possibly protein, fermentation is occurring in the human large intestine, principally in the caecum and ascending colon and that the large bowel may have a greater role to play in digestion than has previously been ascribed to it.
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There are close parallels between the fermentative processes which go on in the rumen, caecum, and colon of herbivorous animals and colonic metabolism in man. Short chain fatty acids, which are the main end-product of carbohydrate breakdown in these organs, exert a controlling influence on intraluminal events, absorption, mucosal metabolism, and are accepted as such by animal physiologists. Such recognition has yet to be given to this aspect of colonic function in man, and many studies of colonic metabolism have failed to take account of the possible effect of short chain fatty acids. A great deal still needs to be learnt about these acids in the human colon - in particular, the overall amount produced each day, the main substrates for fermentation, the effect of diet, the molecular form in which they are absorbed, their contribution to energy metabolism, and their interaction with a wide range of other colonic events. Such knowledge should yield important information which may be relevant to the aetiology of colonic disorders which are so prevalent in the human species.
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Although dietary recommendations for diabetics stress the need for increased carbohydrate and dietary fiber, the effectiveness of dietary fiber in improving insulin sensitivity remains controversial. The aim of this study was to compare the effects of a soluble fiber (guar gum) and an insoluble fiber (wheat bran) on insulin sensitivity in streptozotocin-induced (STZ) diabetic rats. Consequently, the rats were divided into two groups and one half were rendered diabetic with streptozotocin. The STZ diabetic and nondiabetic rats were further randomized and fed a diet containing dietary fiber (7 g/100 g diet) from either guar gum or wheat bran. The hyperinsulinemic clamp technique, combined with infusion of the glucose analog, 2-deoxyglucose (2DG), was utilized to examine insulin sensitivity. Bran-fed STZ diabetic rats were significantly (P < 0.001) hyperglycemic, which was ameliorated by guar gum. Insulin-mediated glucose disposal was increased by the guar diet compared with the bran diet in both the STZ diabetic rats [17.7 +/- 2.2 vs. 11.8 +/- 2.4 mL/(kg x min), P < 0.05] and the nondiabetic rats [20.5 +/- 2.8 vs. 15.5 +/- 1.5 mL/(kg x min), P < 0.05]. The accumulation of 2DG in peripheral muscles reflected the changes in insulin sensitivity with a trend for increased 2DG uptake in the majority of analyzed tissues in rats fed the guar diet, both nondiabetic and STZ diabetic, compared with the bran-fed rats. Accompanying these alterations in insulin sensitivity, guar gum suppressed food intake in the hyperphagic diabetic rats by 20% (P < 0.001). The present results demonstrate the effectiveness of guar gum in improving insulin sensitivity in STZ diabetic rats and suggest that reduced food intake may be an important mechanism of action of guar in hyperphagic diabetic rats.
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Resistant starch (RS) is starch and products of its small intestinal digestion that enter the large bowel. It occurs for various reasons including chemical structure, cooking of food, chemical modification, and food mastication. Human colonic bacteria ferment RS and nonstarch polysaccharides (NSP; major components of dietary fiber) to short-chain fatty acids (SCFA), mainly acetate, propionate, and butyrate. SCFA stimulate colonic blood flow and fluid and electrolyte uptake. Butyrate is a preferred substrate for colonocytes and appears to promote a normal phenotype in these cells. Fermentation of some RS types favors butyrate production. Measurement of colonic fermentation in humans is difficult, and indirect measures (e.g., fecal samples) or animal models have been used. Of the latter, rodents appear to be of limited value, and pigs or dogs are preferable. RS is less effective than NSP in stool bulking, but epidemiological data suggest that it is more protective against colorectal cancer, possibly via butyrate. RS is a prebiotic, but knowledge of its other interactions with the microflora is limited. The contribution of RS to fermentation and colonic physiology seems to be greater than that of NSP. However, the lack of a generally accepted analytical procedure that accommodates the major influences on RS means this is yet to be established.
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Leptin is an adipose-derived hormone that regulates a wide variety of physiological processes, including feeding behavior, metabolic rate, sympathetic nerve activity, reproduction, and immune response. Circulating leptin levels are tightly regulated according to energy homeostasis in vivo. Although mechanisms for the regulation of leptin production in adipocytes are not well understood, G protein-coupled receptors may play an important role in this adipocyte function. Here we report that C2-C6 short-chain fatty acids, ligands of an orphan G protein-coupled receptor GPR41, stimulate leptin expression in both a mouse adipocyte cell line and mouse adipose tissue in primary culture. Acute oral administration of propionate increases circulating leptin levels in mice. The concentrations of short-chain fatty acids required to stimulate leptin production are within physiological ranges, suggesting the relevance of this pathway in vivo.
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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
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Germ-free mice were maintained on polysaccharide-rich or simple-sugar diets and colonized for 10 days with an organism also found in human guts, Bacteroides thetaiotaomicron, followed by whole-genome transcriptional profiling of bacteria and mass spectrometry of cecal glycans. We found that these bacteria assembled on food particles and mucus, selectively induced outer-membrane polysaccharide-binding proteins and glycoside hydrolases, prioritized the consumption of liberated hexose sugars, and revealed a capacity to turn to host mucus glycans when polysaccharides were absent from the diet. This flexible foraging behavior should contribute to ecosystem stability and functional diversity.
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The constellation of metabolic abnormalities including centrally distributed obesity, decreased high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, elevated blood pressure (BP), and hyperglycaemia is known as the metabolic syndrome. Associated with a 3 fold and 2 fold increase in type 2 diabetes and cardiovascular disease (CVD), respectively, it is thought to be a driver of the modern day epidemics of diabetes and CVD and has become a major public health challenge around the world. Since its initial description, several definitions of the syndrome have emerged. Each of these definitions used differing sets of criteria, which reflected contrasting views on pathogenic mechanisms and the need for clinical usefulness. The use of these definitions to conduct research into the metabolic syndrome in diverse populations resulted in wide ranging prevalence rates, inconsistencies and confusion, and spurred on the vigorous debate regarding how the metabolic syndrome should be defined. In response to this controversy, the International Diabetes Federation (IDF) has recently proposed a new definition, which is applicable to populations around the world. It is envisaged that the development of the new definition for the metabolic syndrome will help resolve the confusion caused by the number of earlier attempts to define this important entity.