Prebiotic Supplementation During Pregnancy Modifies the Gut Microbiota and Increases Metabolites in Amniotic Fluid, Driving a Tolerogenic Environment In Utero

The gut microbiota is influenced by environmental factors such as food. Maternal diet during pregnancy modifies the gut microbiota composition and function, leading to the production of specific compounds that are transferred to the fetus and enhance the ontogeny and maturation of the immune system. Prebiotics are fermented by gut bacteria, leading to the release of short-chain fatty acids that can specifically interact with the immune system, inducing a switch toward tolerogenic populations and therefore conferring health benefits. In this study, pregnant BALB/cJRj mice were fed either a control diet or a diet enriched in prebiotics (Galacto-oligosaccharides/Inulin). We hypothesized that galacto-oligosaccharides/inulin supplementation during gestation could modify the maternal microbiota, favoring healthy immune imprinting in the fetus. Galacto-oligosaccharides/inulin supplementation during gestation increases the abundance of Bacteroidetes and decreases that of Firmicutes in the gut microbiota, leading to increased production of fecal acetate, which was found for the first time in amniotic fluid. Prebiotic supplementation increased the abundance of regulatory B and T cells in gestational tissues and in the fetus. Interestingly, these regulatory cells remained later in life. In conclusion, prebiotic supplementation during pregnancy leads to the transmission of specific microbial and immune factors from mother to child, allowing the establishment of tolerogenic immune imprinting in the fetus that may be beneficial for infant health outcomes.

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Gastrointestinal Interaction between Dietary Amino Acids and Gut Microbiota: With Special Emphasis on Host Nutrition

Current Protein and Peptide Science ◽

10.2174/1389203721666200212095503 ◽

2020 ◽

Vol 21 (8) ◽

pp. 785-798 ◽

Cited By ~ 1

Author(s):

Abedin Abdallah ◽

Evera Elemba ◽

Qingzhen Zhong ◽

Zewei Sun

Keyword(s):

Amino Acids ◽

Fatty Acids ◽

Immune System ◽

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Nutrition And Health ◽

Nitrogenous Compounds ◽

Dietary Amino Acids ◽

Host Nutrition ◽

Chain Fatty Acids

The gastrointestinal tract (GIT) of humans and animals is host to a complex community of different microorganisms whose activities significantly influence host nutrition and health through enhanced metabolic capabilities, protection against pathogens, and regulation of the gastrointestinal development and immune system. New molecular technologies and concepts have revealed distinct interactions between the gut microbiota and dietary amino acids (AAs) especially in relation to AA metabolism and utilization in resident bacteria in the digestive tract, and these interactions may play significant roles in host nutrition and health as well as the efficiency of dietary AA supplementation. After the protein is digested and AAs and peptides are absorbed in the small intestine, significant levels of endogenous and exogenous nitrogenous compounds enter the large intestine through the ileocaecal junction. Once they move in the colonic lumen, these compounds are not markedly absorbed by the large intestinal mucosa, but undergo intense proteolysis by colonic microbiota leading to the release of peptides and AAs and result in the production of numerous bacterial metabolites such as ammonia, amines, short-chain fatty acids (SCFAs), branched-chain fatty acids (BCFAs), hydrogen sulfide, organic acids, and phenols. These metabolites influence various signaling pathways in epithelial cells, regulate the mucosal immune system in the host, and modulate gene expression of bacteria which results in the synthesis of enzymes associated with AA metabolism. This review aims to summarize the current literature relating to how the interactions between dietary amino acids and gut microbiota may promote host nutrition and health.

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The Influence of Diet and Sex on the Gut Microbiota of Lean and Obese JCR:LA-cp Rats

Microorganisms ◽

10.3390/microorganisms9051037 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1037

Author(s):

Craig Resch ◽

Mihir Parikh ◽

J. Alejandro Austria ◽

Spencer D. Proctor ◽

Thomas Netticadan ◽

...

Keyword(s):

Gut Microbiota ◽

Control Diet ◽

Bacterial Species ◽

Alpha Diversity ◽

Short Chain Fatty Acids ◽

Female Rats ◽

Dependent Manner ◽

Male And Female ◽

Ground Flaxseed ◽

The Impact

There is an increased interest in the gut microbiota as it relates to health and obesity. The impact of diet and sex on the gut microbiota in conjunction with obesity also demands extensive systemic investigation. Thus, the influence of sex, diet, and flaxseed supplementation on the gut microbiota was examined in the JCR:LA-cp rat model of genetic obesity. Male and female obese rats were randomized into four groups (n = 8) to receive, for 12 weeks, either (a) control diet (Con), (b) control diet supplemented with 10% ground flaxseed (CFlax), (c) a high-fat, high sucrose (HFHS) diet, or (d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. Illumine MiSeq sequencing revealed a richer microbiota in rats fed control diets rather than HFHS diets. Obese female rats had lower alpha-diversity than lean female; however, both sexes of obese and lean JCR rats differed significantly in β-diversity, as their gut microbiota was composed of different abundances of bacterial types. The feeding of an HFHS diet affected the diversity by increasing the phylum Bacteroidetes and reducing bacterial species from phylum Firmicutes. Fecal short-chain fatty acids such as acetate, propionate, and butyrate-producing bacterial species were correspondingly impacted by the HFHS diet. Flax supplementation improved the gut microbiota by decreasing the abundance of Blautia and Eubacterium dolichum. Collectively, our data show that an HFHS diet results in gut microbiota dysbiosis in a sex-dependent manner. Flaxseed supplementation to the diet had a significant impact on gut microbiota diversity under both flax control and HFHS dietary conditions.

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The Microbiotic Highway to Health—New Perspective on Food Structure, Gut Microbiota, and Host Inflammation

Nutrients ◽

10.3390/nu10111590 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1590 ◽

Cited By ~ 13

Author(s):

Nina Hansen ◽

Anette Sams

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Dietary Habits ◽

Gut Hormones ◽

Host Immune System ◽

Inflammatory Conditions ◽

Food Structure ◽

New Perspective ◽

And Function ◽

The Impact

This review provides evidence that not only the content of nutrients but indeed the structural organization of nutrients is a major determinant of human health. The gut microbiota provides nutrients for the host by digesting food structures otherwise indigestible by human enzymes, thereby simultaneously harvesting energy and delivering nutrients and metabolites for the nutritional and biological benefit of the host. Microbiota-derived nutrients, metabolites, and antigens promote the development and function of the host immune system both directly by activating cells of the adaptive and innate immune system and indirectly by sustaining release of monosaccharides, stimulating intestinal receptors and secreting gut hormones. Multiple indirect microbiota-dependent biological responses contribute to glucose homeostasis, which prevents hyperglycemia-induced inflammatory conditions. The composition and function of the gut microbiota vary between individuals and whereas dietary habits influence the gut microbiota, the gut microbiota influences both the nutritional and biological homeostasis of the host. A healthy gut microbiota requires the presence of beneficial microbiotic species as well as vital food structures to ensure appropriate feeding of the microbiota. This review focuses on the impact of plant-based food structures, the “fiber-encapsulated nutrient formulation”, and on the direct and indirect mechanisms by which the gut microbiota participate in host immune function.

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Dietary lipids, gut microbiota and lipid metabolism

Reviews in Endocrine and Metabolic Disorders ◽

10.1007/s11154-019-09512-0 ◽

2019 ◽

Vol 20 (4) ◽

pp. 461-472 ◽

Cited By ~ 40

Author(s):

Marc Schoeler ◽

Robert Caesar

Keyword(s):

Fatty Acids ◽

Lipid Metabolism ◽

Liver Disease ◽

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Dietary Lipids ◽

Lipid Levels ◽

And Function ◽

Host Metabolism ◽

Secondary Bile Acids

Abstract The gut microbiota is a central regulator of host metabolism. The composition and function of the gut microbiota is dynamic and affected by diet properties such as the amount and composition of lipids. Hence, dietary lipids may influence host physiology through interaction with the gut microbiota. Lipids affect the gut microbiota both as substrates for bacterial metabolic processes, and by inhibiting bacterial growth by toxic influence. The gut microbiota has been shown to affect lipid metabolism and lipid levels in blood and tissues, both in mice and humans. Furthermore, diseases linked to dyslipidemia, such as non-alcoholic liver disease and atherosclerosis, are associated with changes in gut microbiota profile. The influence of the gut microbiota on host lipid metabolism may be mediated through metabolites produced by the gut microbiota such as short-chain fatty acids, secondary bile acids and trimethylamine and by pro-inflammatory bacterially derived factors such as lipopolysaccharide. Here we will review the association between gut microbiota, dietary lipids and lipid metabolism

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The gut microbiota influences skeletal muscle mass and function in mice

Science Translational Medicine ◽

10.1126/scitranslmed.aan5662 ◽

2019 ◽

Vol 11 (502) ◽

pp. eaan5662 ◽

Cited By ~ 37

Author(s):

Shawon Lahiri ◽

Hyejin Kim ◽

Isabel Garcia-Perez ◽

Musarrat Maisha Reza ◽

Katherine A. Martin ◽

...

Keyword(s):

Skeletal Muscle ◽

Neuromuscular Junction ◽

Gut Microbiota ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Neuromuscular Junctions ◽

Short Chain Fatty Acids ◽

Germ Free ◽

Mouse Skeletal Muscle ◽

And Function

The functional interactions between the gut microbiota and the host are important for host physiology, homeostasis, and sustained health. We compared the skeletal muscle of germ-free mice that lacked a gut microbiota to the skeletal muscle of pathogen-free mice that had a gut microbiota. Compared to pathogen-free mouse skeletal muscle, germ-free mouse skeletal muscle showed atrophy, decreased expression of insulin-like growth factor 1, and reduced transcription of genes associated with skeletal muscle growth and mitochondrial function. Nuclear magnetic resonance spectrometry analysis of skeletal muscle, liver, and serum from germ-free mice revealed multiple changes in the amounts of amino acids, including glycine and alanine, compared to pathogen-free mice. Germ-free mice also showed reduced serum choline, the precursor of acetylcholine, the key neurotransmitter that signals between muscle and nerve at neuromuscular junctions. Reduced expression of genes encoding Rapsyn and Lrp4, two proteins important for neuromuscular junction assembly and function, was also observed in skeletal muscle from germ-free mice compared to pathogen-free mice. Transplanting the gut microbiota from pathogen-free mice into germ-free mice resulted in an increase in skeletal muscle mass, a reduction in muscle atrophy markers, improved oxidative metabolic capacity of the muscle, and elevated expression of the neuromuscular junction assembly genes Rapsyn and Lrp4. Treating germ-free mice with short-chain fatty acids (microbial metabolites) partly reversed skeletal muscle impairments. Our results suggest a role for the gut microbiota in regulating skeletal muscle mass and function in mice.

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Immunomodulation by Gut Microbiota: Role of Toll-Like Receptor Expressed by T Cells

Journal of Immunology Research ◽

10.1155/2014/586939 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 23

Author(s):

Mariagrazia Valentini ◽

Alessia Piermattei ◽

Gabriele Di Sante ◽

Giuseppe Migliara ◽

Giovanni Delogu ◽

...

Keyword(s):

T Cells ◽

Immune System ◽

Gut Microbiota ◽

Cell Types ◽

Mutual Regulation ◽

Close Relationship ◽

Numerous Cell ◽

Specific Receptors ◽

And Function

A close relationship exists between gut microbiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gut microbiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs), pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota.

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Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier

Frontiers in Nutrition ◽

10.3389/fnut.2021.718356 ◽

2021 ◽

Vol 8 ◽

Author(s):

Giovanni Barbara ◽

Maria Raffaella Barbaro ◽

Daniele Fuschi ◽

Marta Palombo ◽

Francesca Falangone ◽

...

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Cell Damage ◽

Short Chain Fatty Acids ◽

The Body ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Inflammatory Bowel ◽

Irritable Bowel

The intestinal epithelial barrier (IEB) is one of the largest interfaces between the environment and the internal milieu of the body. It is essential to limit the passage of harmful antigens and microorganisms and, on the other side, to assure the absorption of nutrients and water. The maintenance of this delicate equilibrium is tightly regulated as it is essential for human homeostasis. Luminal solutes and ions can pass across the IEB via two main routes: the transcellular pathway or the paracellular pathway. Tight junctions (TJs) are a multi-protein complex responsible for the regulation of paracellular permeability. TJs control the passage of antigens through the IEB and have a key role in maintaining barrier integrity. Several factors, including cytokines, gut microbiota, and dietary components are known to regulate intestinal TJs. Gut microbiota participates in several human functions including the modulation of epithelial cells and immune system through the release of several metabolites, such as short-chain fatty acids (SCFAs). Mediators released by immune cells can induce epithelial cell damage and TJs dysfunction. The subsequent disruption of the IEB allows the passage of antigens into the mucosa leading to further inflammation. Growing evidence indicates that dysbiosis, immune activation, and IEB dysfunction have a role in several diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gluten-related conditions. Here we summarize the interplay between the IEB and gut microbiota and mucosal immune system and their involvement in IBS, IBD, and gluten-related disorders.

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Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial

10.2337/figshare.14340419 ◽

2021 ◽

Author(s):

Noel T. Mueller ◽

Moira K. Differding ◽

Mingyu Zhang ◽

Nisa Maruthar ◽

Stephen P Juraschek ◽

...

Keyword(s):

Weight Loss ◽

Gut Microbiota ◽

Randomized Trial ◽

Short Chain Fatty Acids ◽

Metagenomic Sequencing ◽

Microbiota Composition ◽

Behavioral Weight Loss ◽

Microbiome Composition ◽

Weight Loss Group ◽

And Function

Objective: To determine the longer-term effects of metformin and behavioral weight loss on gut microbiota and SCFAs. Methods: We conducted a parallel-arm, randomized trial. We enrolled overweight/obese adults who had been treated for solid tumors but had no ongoing cancer treatment and randomized them (n=121) to: 1) metformin (up to 2000mg), 2) coach-directed behavioral weight loss, or 3) self-directed care (control) for 12 months. We collected stool and serum at baseline (n=114), 6 months (n=109) and 12 months (n=105). From stool, we extracted microbial DNA and conducted amplicon and metagenomic sequencing. We measured SCFAs and other biochemical parameters from fasting serum. Results: Of the 121 participants, 79% were female, 46% were black, and the mean age was 60y. Only metformin intervention significantly altered microbiota composition. Compared to control, metformin increased E. Coli and Ruminococcus torques and decreased Intestinibacter Bartletti at both 6 and 12 months, and decreased the genus Roseburia (genus), including R. faecis and R. intestinalis, at 12 months. Effects were similar when comparing metformin to the behavioral weight loss group. Metformin also altered 62 metagenomic functional pathways and increased butyrate, acetate, and valerate at 6 months. Behavioral weight loss vs. control did not significantly alter microbiota composition, but did increase acetate at 6 months. Increases in acetate were associated with decreases in fasting insulin. Conclusions: Metformin, but not behavioral weight loss, impacted gut microbiota composition and function at 6 months and 12 months. Both metformin and behavioral weight loss altered 6-month SCFAs, including increasing acetate which correlated with improved insulin sensitivity.

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Effects of Altered Dietary Fiber on the Gut Microbiota, Short-Chain Fatty Acids and Cecum of Chickens during Different Growth Periods

10.20944/preprints202002.0109.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Baosheng Sun ◽

Linyue Hou ◽

Yu Yang

Keyword(s):

Gut Microbiota ◽

Dietary Fiber ◽

Total Content ◽

Short Chain Fatty Acids ◽

Gut Health ◽

High Fiber ◽

High Feed ◽

Long Term Observation ◽

And Function

Increasing numbers of researchers are interested in the importance of dietary fiber for the gut microbiota, microbiotal metabolite SCFA, energy metabolism and gut health of the host. However, studies have demonstrated that long-term and longitudinal observation may be needed to evaluate the effect of dietary fiber better, and few such works have been made in chickens. Therefore, we successively fed low-fiber, high--fiber and low-fiber diets to two breeds of chickens during different growth periods (1—8, 9—20 and 21—50 weeks), aiming to longitudinally observe the long-term effect of altered dietary fiber on the gut microbiota, SCFA and development of cecum of chickens with age. The results showed that the composition and function of the gut microbiota, SCFA and the development of the cecum were different during different periods, which was largly affected by dietary fiber. However, the causes of some effects were different during the different periods. For example, compared with that in low-fiber chickens at 8 weeks, dominant fiber-degradation bacteria such as Bacteroidetes, Alloprevotella and SCFA-producing bacteria such as Faecalibacterium increased due to a high-fiber diet at 20 weeks, while due to a high feed intake in 50 weeks. Moreover, the concentration of SCFA in 20 weeks was significantly higher than in 8 weeks and 50 weeks, but the causes of this difference were also distinct. It was proposed that a long-term observation was needed to evaluate the effect of dietary fiber better on chickens. The metabolite pathways of ATP-binding cassette (ABC) transporters encoded by Firmicutes were enriched in 8 weeks, while a two-component system and β–glucosidase encoded by Bacteroidetes were enriched in 20 and 50 weeks. The trend was the same in two breeds of chickens except for Alloprevotella. In addition, the total content of SCFA in the contents of cecum was also affected by the size of the cecum. Surprisingly, the length of the cecum shortened from 20—50 weeks, maybe due to reduced dietary fiber.

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Modulation of the Gut Microbiota by Olive Oil Phenolic Compounds: Implications for Lipid Metabolism, Immune System, and Obesity

Nutrients ◽

10.3390/nu12082200 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2200

Author(s):

Marta Farràs ◽

Laura Martinez-Gili ◽

Kevin Portune ◽

Sara Arranz ◽

Gary Frost ◽

...

Keyword(s):

Clinical Trials ◽

Immune System ◽

Lipid Metabolism ◽

Phenolic Compounds ◽

Gut Microbiota ◽

Olive Oil ◽

Cholesterol Metabolism ◽

Virgin Olive Oil ◽

Short Chain Fatty Acids ◽

Beneficial Effects

There is extensive information of the beneficial effects of virgin olive oil (VOO), especially on cardiovascular diseases. Some VOO healthy properties have been attributed to their phenolic-compounds (PCs). The aim of this review is to present updated data on the effects of olive oil (OO) PCs on the gut microbiota, lipid metabolism, immune system, and obesity, as well as on the crosstalk among them. We summarize experiments and clinical trials which assessed the specific effects of the olive oil phenolic-compounds (OOPCs) without the synergy with OO-fats. Several studies have demonstrated that OOPC consumption increases Bacteroidetes and/or reduces the Firmicutes/Bacteroidetes ratio, which have both been related to atheroprotection. OOPCs also increase certain beneficial bacteria and gut-bacteria diversity which can be therapeutic for lipid-immune disorders and obesity. Furthermore, some of the mechanisms implicated in the crosstalk between OOPCs and these disorders include antimicrobial-activity, cholesterol microbial metabolism, and metabolites produced by bacteria. Specifically, OOPCs modulate short-chain fatty-acids produced by gut-microbiota, which can affect cholesterol metabolism and the immune system, and may play a role in weight gain through promoting satiety. Since data in humans are scarce, there is a necessity for more clinical trials designed to assess the specific role of the OOPCs in this crosstalk.

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