scholarly journals Intestinal Microbiota Shapes Gut Physiology and Regulates Enteric Neurons and Glia

2020 ◽  
Author(s):  
Fernando Vicentini ◽  
Catherine Keenan ◽  
Laurie Wallace ◽  
Crystal Woods ◽  
Jean-Baptiste Cavin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Neuronal Survival ◽  
Neuronal Loss ◽  
Structure And Function ◽  
Enteric Neurons ◽  
Intestinal Function ◽  
Gi Tract ◽  
Enteric Glia ◽  
And Function

Abstract Background: The intestinal microbiota plays an important role in regulating gastrointestinal (GI) physiology in part through interactions with the enteric nervous system (ENS). Alterations in the gut microbiome frequently occur together with disturbances in enteric neural control in pathophysiological conditions. However, the mechanisms by which the microbiota regulates GI function and the structure of the ENS are incompletely understood. Using a mouse model of antibiotic (Abx)-induced bacterial depletion, we sought to determine the molecular mechanisms of microbial regulation of intestinal function and the integrity of the ENS. Spontaneous reconstitution of the Abx-depleted microbiota was used to assess the plasticity of structure and function of the GI tract and neuronal survival and neurogenesis in the ENS. Results: Adult male and female Abx-treated mice exhibited alterations in GI structure and function, including a longer small intestine, slower transit time, increased carbachol-stimulated ion transport and increased intestinal permeability. These alterations were accompanied by the loss of enteric neurons in the ileum and proximal colon in both submucosal and myenteric plexuses. A reduction in the number of enteric glia were only observed in the ileal myenteric plexus. Recovery of the microbiota restored intestinal function and stimulated enteric neurogenesis leading to increases in the number of enteric glia and neurons. Lipopolysaccharide (LPS) supplementation enhanced neuronal survival alongside bacterial depletion but had no effect on neuronal recovery once the Abx-induced neuronal loss was established. In contrast, SCFA were able to restore neuronal numbers after Abx-induced neuronal loss, demonstrating that SCFA stimulate enteric neurogenesis in vivo. Conclusions: Our results demonstrate a role for the gut microbiota in regulating the structure function of the GI tract in a sex-independent manner. Moreover, the microbiota is essential for the maintenance of ENS integrity, by regulating enteric neuronal survival and promoting neurogenesis. Molecular determinants of the microbiota, LPS and SCFA, regulate enteric neuronal survival, while SCFA also stimulates neurogenesis. Our data reveal new insights into the role of the gut microbiota that could lead to therapeutic developments for the treatment of enteric neuropathies.

scholarly journals Intestinal microbiota shapes gut physiology and regulates enteric neurons and glia

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Fernando A. Vicentini ◽  
Catherine M. Keenan ◽  
Laurie E. Wallace ◽  
Crystal Woods ◽  
Jean-Baptiste Cavin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Neuronal Survival ◽  
Neuronal Loss ◽  
Structure And Function ◽  
Enteric Neurons ◽  
Intestinal Function ◽  
Gi Tract ◽  
Enteric Glia ◽  
And Function

Abstract Background The intestinal microbiota plays an important role in regulating gastrointestinal (GI) physiology in part through interactions with the enteric nervous system (ENS). Alterations in the gut microbiome frequently occur together with disturbances in enteric neural control in pathophysiological conditions. However, the mechanisms by which the microbiota regulates GI function and the structure of the ENS are incompletely understood. Using a mouse model of antibiotic (Abx)-induced bacterial depletion, we sought to determine the molecular mechanisms of microbial regulation of intestinal function and the integrity of the ENS. Spontaneous reconstitution of the Abx-depleted microbiota was used to assess the plasticity of structure and function of the GI tract and ENS. Microbiota-dependent molecular mechanisms of ENS neuronal survival and neurogenesis were also assessed. Results Adult male and female Abx-treated mice exhibited alterations in GI structure and function, including a longer small intestine, slower transit time, increased carbachol-stimulated ion secretion, and increased intestinal permeability. These alterations were accompanied by the loss of enteric neurons in the ileum and proximal colon in both submucosal and myenteric plexuses. A reduction in the number of enteric glia was only observed in the ileal myenteric plexus. Recovery of the microbiota restored intestinal function and stimulated enteric neurogenesis leading to increases in the number of enteric glia and neurons. Lipopolysaccharide (LPS) supplementation enhanced neuronal survival alongside bacterial depletion, but had no effect on neuronal recovery once the Abx-induced neuronal loss was established. In contrast, short-chain fatty acids (SCFA) were able to restore neuronal numbers after Abx-induced neuronal loss, demonstrating that SCFA stimulate enteric neurogenesis in vivo. Conclusions Our results demonstrate a role for the gut microbiota in regulating the structure and function of the GI tract in a sex-independent manner. Moreover, the microbiota is essential for the maintenance of ENS integrity, by regulating enteric neuronal survival and promoting neurogenesis. Molecular determinants of the microbiota, LPS and SCFA, regulate enteric neuronal survival, while SCFA also stimulates neurogenesis. Our data reveal new insights into the role of the gut microbiota that could lead to therapeutic developments for the treatment of enteric neuropathies.

scholarly journals Intestinal Microbiota Shapes Gut Physiology and Regulates Enteric Neurons and Glia

2021 ◽  
Author(s):  
Fernando A. Vicentini ◽  
Catherine M. Keenan ◽  
Laurie Wallace ◽  
Crystal Woods ◽  
Jean-Baptiste Cavin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Neuronal Survival ◽  
Neuronal Loss ◽  
Structure And Function ◽  
Enteric Neurons ◽  
Intestinal Function ◽  
Gi Tract ◽  
Enteric Glia ◽  
And Function

Abstract Background: The intestinal microbiota plays an important role in regulating gastrointestinal (GI) physiology in part through interactions with the enteric nervous system (ENS). Alterations in the gut microbiome frequently occur together with disturbances in enteric neural control in pathophysiological conditions. However, the mechanisms by which the microbiota regulates GI function and the structure of the ENS are incompletely understood. Using a mouse model of antibiotic (Abx)-induced bacterial depletion, we sought to determine the molecular mechanisms of microbial regulation of intestinal function and the integrity of the ENS. Spontaneous reconstitution of the Abx-depleted microbiota was used to assess the plasticity of structure and function of the GI tract and ENS. Microbiota-dependent molecular mechanisms of ENS neuronal survival and neurogenesis were also assessed. Results: Adult male and female Abx-treated mice exhibited alterations in GI structure and function, including a longer small intestine, slower transit time, increased carbachol-stimulated ion secretion and increased intestinal permeability. These alterations were accompanied by the loss of enteric neurons in the ileum and proximal colon in both submucosal and myenteric plexuses. A reduction in the number of enteric glia were only observed in the ileal myenteric plexus. Recovery of the microbiota restored intestinal function and stimulated enteric neurogenesis leading to increases in the number of enteric glia and neurons. Lipopolysaccharide (LPS) supplementation enhanced neuronal survival alongside bacterial depletion, but had no effect on neuronal recovery once the Abx-induced neuronal loss was established. In contrast, short-chain fatty acids (SCFA) were able to restore neuronal numbers after Abx-induced neuronal loss, demonstrating that SCFA stimulate enteric neurogenesis in vivo.Conclusions: Our results demonstrate a role for the gut microbiota in regulating the structure and function of the GI tract in a sex-independent manner. Moreover, the microbiota is essential for the maintenance of ENS integrity, by regulating enteric neuronal survival and promoting neurogenesis. Molecular determinants of the microbiota, LPS and SCFA, regulate enteric neuronal survival, while SCFA also stimulates neurogenesis. Our data reveal new insights into the role of the gut microbiota that could lead to therapeutic developments for the treatment of enteric neuropathies.

scholarly journals Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity

mSystems ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Jingwei Cai ◽  
Robert G. Nichols ◽  
Imhoi Koo ◽  
Zachary A. Kalikow ◽  
Limin Zhang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Flow Cytometry ◽  
Free Radical ◽  
Gut Microbiota ◽  
Structure And Function ◽  
Metabolic Phenotyping ◽  
And Function

ABSTRACTThe gut microbiota is susceptible to modulation by environmental stimuli and therefore can serve as a biological sensor. Recent evidence suggests that xenobiotics can disrupt the interaction between the microbiota and host. Here, we describe an approach that combinesin vitromicrobial incubation (isolated cecal contents from mice), flow cytometry, and mass spectrometry- and1H nuclear magnetic resonance (NMR)-based metabolomics to evaluate xenobiotic-induced microbial toxicity. Tempol, a stabilized free radical scavenger known to remodel the microbial community structure and functionin vivo, was studied to assess its direct effect on the gut microbiota. The microbiota was isolated from mouse cecum and was exposed to tempol for 4 h under strict anaerobic conditions. The flow cytometry data suggested that short-term tempol exposure to the microbiota is associated with disrupted membrane physiology as well as compromised metabolic activity. Mass spectrometry and NMR metabolomics revealed that tempol exposure significantly disrupted microbial metabolic activity, specifically indicated by changes in short-chain fatty acids, branched-chain amino acids, amino acids, nucleotides, glucose, and oligosaccharides. In addition, a mouse study with tempol (5 days gavage) showed similar microbial physiologic and metabolic changes, indicating that thein vitroapproach reflectedin vivoconditions. Our results, through evaluation of microbial viability, physiology, and metabolism and a comparison ofin vitroandin vivoexposures with tempol, suggest that physiologic and metabolic phenotyping can provide unique insight into gut microbiota toxicity.IMPORTANCEThe gut microbiota is modulated physiologically, compositionally, and metabolically by xenobiotics, potentially causing metabolic consequences to the host. We recently reported that tempol, a stabilized free radical nitroxide, can exert beneficial effects on the host through modulation of the microbiome community structure and function. Here, we investigated a multiplatform phenotyping approach that combines high-throughput global metabolomics with flow cytometry to evaluate the direct effect of tempol on the microbiota. This approach may be useful in deciphering how other xenobiotics directly influence the microbiota.

Ongoing Supplementation of Probiotics to Cesarean-Born Neonates during the First Month of Life may Impact the Gut Microbial

2020 ◽  
Author(s):  
Wenqing Yang ◽  
Liang Tian ◽  
Jiao Luo ◽  
Jialin Yu
Keyword(s):  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Influencing Factor ◽  
Delivery Mode ◽  
Next Generation Sequencing Technology ◽  
Operational Taxonomic Units ◽  
Β Diversity ◽  
Α Diversity ◽  
Clusters Of Orthologous Groups ◽  
And Function

Objective The delivery mode is considered to be a significant influencing factor in the early gut microbiota composition, which is associated with the long-term health of the host. In this study, we tried to explore the effects of probiotics on the intestinal microbiota of C-section neonates. Study Design Twenty-six Chinese neonates were enrolled in this study. The neonates were divided into four groups: VD (natural delivery neonates, n = 3), CD (cesarean-born neonates, n = 9), CDL (cesarean-born neonates supplemented with probiotic at a lower dosage, n = 7), and CDH (cesarean-born neonates supplemented with probiotic at a higher dosage, n = 7). Fecal samples were collected on the 3rd, 7th, and 28th day since birth. The V3–V4 region of the 16S ribosomal ribonucleic acid gene was sequenced by next-generation sequencing technology. Results The α-diversity of the intestinal microbiota of cesarean delivery neonates was significantly lower than that of the naturally delivered neonates on the 28th day (p = 0.005). After supplementation with probiotics for 28 days, the α-diversity and the β-diversity of the gut flora in the cesarean-born infants (CDL28 and CDH28) was similar to that in the vaginally delivery infants. Meanwhile, the abundances of Lactobacillus and Bifidobacterium were significantly increased since the 3rd day of probiotic supplementation. Besides, the sustained supplementation of probiotics to neonates would help improve the abundance of the operational taxonomic units in several different Clusters of Orthologous Groups of proteins. Conclusion This study showed that probiotics supplementation to cesarean-born neonates since birth might impact the diversity and function of gut microbiota. Key Points

scholarly journals Dietary Gluten as a Conditioning Factor of the Gut Microbiota in Celiac Disease

2019 ◽  
Author(s):  
Karla A Bascuñán ◽  
Magdalena Araya ◽  
Leda Roncoroni ◽  
Luisa Doneda ◽  
Luca Elli
Keyword(s):  
Celiac Disease ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Current Knowledge ◽  
Current Treatment ◽  
Current Evidence ◽  
Environmental Trigger ◽  
Relevant Role ◽  
Intimate Relation ◽  
And Function

ABSTRACT The gut microbiota plays a relevant role in determining an individual's health status, and the diet is a major factor in modulating the composition and function of gut microbiota. Gluten constitutes an essential dietary component in Western societies and is the environmental trigger of celiac disease. The presence/absence of gluten in the diet can change the diversity and proportions of the microbial communities constituting the gut microbiota. There is an intimate relation between gluten metabolism and celiac disease pathophysiology and gut microbiota; their interrelation defines intestinal health and homeostasis. Environmental factors modify the intestinal microbiota and, in turn, its changes modulate the mucosal and immune responses. Current evidence from studies of young and adult patients with celiac disease increasingly supports that dysbiosis (i.e., compositional and functional alterations of the gut microbiome) is present in celiac disease, but to what extent this is a cause or consequence of the disease and whether the different intestinal diseases (celiac disease, ulcerative colitis, Crohn disease) have specific change patterns is not yet clear. The use of bacterial-origin enzymes that help completion of gluten digestion is of interest because of the potential application as coadjuvant in the current treatment of celiac disease. In this narrative review, we address the current knowledge on the complex interaction between gluten digestion and metabolism, celiac disease, and the intestinal microbiota.

scholarly journals Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Kymberleigh A. Romano ◽  
Eugenio I. Vivas ◽  
Daniel Amador-Noguez ◽  
Federico E. Rey
Keyword(s):  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Human Life ◽  
Water Soluble ◽  
Human Gut ◽  
Choline Intake ◽  
Low Levels ◽  
And Function ◽  
Dietary Choline

ABSTRACT Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine-N-oxide (TMAO). Recent studies revealed that TMAO exacerbates atherosclerosis in mice and positively correlates with the severity of this disease in humans. However, which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., genotype) and diet affect TMA production and colonization of these microbes, and the effects TMA-producing microbes have on the bioavailability of dietary choline remain largely unknown. We screened a collection of 79 sequenced human intestinal isolates encompassing the major phyla found in the human gut and identified nine strains capable of producing TMA from choline in vitro. Gnotobiotic mouse studies showed that TMAO accumulates in the serum of animals colonized with TMA-producing species, but not in the serum of animals colonized with intestinal isolates that do not generate TMA from choline in vitro. Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host. This effect was more pronounced as the abundance of TMA-producing bacteria increased. Our findings provide a framework for designing strategies aimed at changing the representation or activity of TMA-producing bacteria in the human gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for humans. IMPORTANCE Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and increased trimethylamine N-oxide (TMAO) levels have been causally linked with CVD development. This work identifies members of the human gut microbiota responsible for both the accumulation of trimethylamine (TMA), the precursor of the proatherogenic compound TMAO, and subsequent decreased choline bioavailability to the host. Understanding how to manipulate the representation and function of choline-consuming, TMA-producing species in the intestinal microbiota could potentially lead to novel means for preventing or treating atherosclerosis and choline deficiency-associated diseases.

scholarly journals Differential Effects of Antibiotic Therapy on the Structure and Function of Human Gut Microbiota

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80201 ◽  
Author(s):  
Ana Elena Pérez-Cobas ◽  
Alejandro Artacho ◽  
Henrik Knecht ◽  
María Loreto Ferrús ◽  
Anette Friedrichs ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Antibiotic Therapy ◽  
Structure And Function ◽  
Human Gut ◽  
Differential Effects ◽  
Human Gut Microbiota ◽  
And Function

scholarly journals Harnessing the gut microbiota to promote metabolic health

2020 ◽  
Vol 78 (Supplement_3) ◽  
pp. 75-78
Author(s):  
Niv Zmora
Keyword(s):  
Gut Microbiota ◽  
Structure And Function ◽  
Metabolic Phenotype ◽  
Metabolic Responses ◽  
Neoplastic Disease ◽  
Compelling Evidence ◽  
Sequencing Technologies ◽  
And Function ◽  
Generation Sequencing

Abstract Precision medicine has become the mainstay of modern therapeutics, especially for neoplastic disease, but this paradigm does not commonly prevail in dietary planning. Compelling evidence suggests that individual features, including the structure and function of the gut microbiota, contribute to harvesting and metabolizing energy from food, and thereby modulate the host metabolic phenotype and glucose homeostasis. Here, the concept of precision to dietary planning is highlighted by demonstrating the role of the microbiota in glucose intolerance in response to noncaloric artificial sweeteners, and by linking the microbiota and other host features to postprandial increases in blood glucose. These findings highlight the heterogeneity that exists among humans, which translates into divergent metabolic responses to similar food and warrants the adoption of next-generation sequencing technologies and advanced bioinformatics to revolutionize nutrition studies, laying the groundwork for an individually focused tailor-made practice.

Anatomy and physiology of the gastrointestinal tract

2021 ◽  
pp. 1-16
Author(s):  
Jennie Burch ◽  
Brigitte Collins
Keyword(s):  
Gastrointestinal Tract ◽  
Gall Bladder ◽  
Abdominal Cavity ◽  
Structure And Function ◽  
Pelvic Cavity ◽  
Gi Tract ◽  
Waste Products ◽  
Anatomy And Physiology ◽  
And Function

The anatomy and physiology of the gastrointestinal (GI) tract chapter provides information on the parts, structure, and function of the gut. The hollow tube of the gastrointestinal tract begins at the mouth and ends at the anus. The GI tract in part lies within the abdominal cavity and the pelvic cavity. There are also the accessory organs of the liver, pancreas, and gall bladder. The nerves, hormones, secretions, and blood supply to the gut are also explored. The role of the GI tract is to ingest food and fluids. These are digested through mechanical and chemical means such as chewing. The nutrients are then absorbed, predominantly in the ileum. Waste products are finally eliminated via the anus.

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