scholarly journals Physical Activity Shapes the Intestinal Microbiome and Immunity of Healthy Mice but Has No Protective Effects against Colitis in MUC2−/− Mice

mSystems ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Mehrbod Estaki ◽  
Douglas W. Morck ◽  
Sanjoy Ghosh ◽  
Candice Quin ◽  
Jason Pither ◽  
...  
Keyword(s):  
Physical Activity ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Intestinal Microbiome ◽  
Protective Effects ◽  
Immune Markers ◽  
Murine Colitis ◽  
Intestinal Mucus ◽  
Chemically Induced ◽  
Inflammatory Bowel

Perturbation in the gut microbial ecosystem has been associated with various diseases, including inflammatory bowel disease. Habitual physical activity, through its ability to modulate the gut microbiome, has recently been shown to prophylactically protect against chemically induced models of murine colitis. Here, we (i) confirm previous reports that physical activity has limited but significant effects on the gut microbiome of mice and (ii) show that such changes are associated with anti-inflammatory states in the gut, such as increased production of beneficial short-chain fatty acids and lower levels of proinflammatory immune markers implicated in human colitis; however, we also show that (iii) these physical activity-derived benefits are completely lost in the absence of a healthy intestinal mucus layer, a hallmark phenotype of human colitis.

scholarly journals Physical activity shapes the intestinal microbiome and immunity of healthy mice but has no protective effects against colitis in MUC2-/- mice

2020 ◽  
Author(s):  
Mehrbod Estaki ◽  
Douglas W. Morck ◽  
Candice Quin ◽  
Jason Pither ◽  
Jacqueline A. Barnett ◽  
...  
Keyword(s):  
Physical Activity ◽  
Wheel Running ◽  
Disease Onset ◽  
Clinical Signs ◽  
Intestinal Microbiome ◽  
Protective Effects ◽  
Chemically Induced ◽  
Mucosal Layer ◽  
Mucin 2 ◽  
Inflammatory State

AbstractThe interactions among humans, their environment, and the trillions of microbes residing within the human intestinal tract form a tripartite relationship that is fundamental to the overall health of the host. Disruptions in the delicate balance between the intestinal microbiota and their host immunity are implicated in various chronic diseases including inflammatory bowel disease (IBD). There is no known cure for IBD, therefore, novel therapeutics targeting prevention and symptoms management are of great interest. Recently, physical activity in healthy mice was shown to be protective against chemically-induced colitis, however the benefits of physical activity during or following disease onset is not known. In this study, we examine whether voluntary wheel running is protective against primary disease symptoms in a mucin 2 deficient (Muc2-/-) life-long model of murine colitis. We show that 6 weeks of wheel running in healthy C57BL/6 mice leads to distinct changes in fecal bacteriome, increased butyrate production, and modulation in colonic gene expression of various cytokines, suggesting an overall primed anti-inflammatory state. However, these physical activity-derived benefits are not present in Muc2-/- mice harboring a dysfunctional mucosal layer from birth, ultimately showing no improvements in clinical signs. We extrapolate from our findings that while physical activity in healthy individuals may be an important preventative measure against IBD, for those with a compromised intestinal mucosa, a commonality in IBD patients, these benefits are lost.

scholarly journals Bugs, genes, fatty acids, and serotonin: Unraveling inflammatory bowel disease?

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1146 ◽  
Author(s):  
Jonathan D. Kaunitz ◽  
Piyush Nayyar
Keyword(s):  
Fatty Acids ◽  
Short Chain Fatty Acids ◽  
Intestinal Microbiome ◽  
Mucosal Barrier ◽  
Neural Systems ◽  
Integrative Approach ◽  
Mucosal Barrier Function ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Glucagon Like Peptide

The annual incidence of the inflammatory bowel diseases (IBDs) ulcerative colitis and Crohn’s disease has increased at an alarming rate. Although the specific pathophysiology underlying IBD continues to be elusive, it is hypothesized that IBD results from an aberrant and persistent immune response directed against microbes or their products in the gut, facilitated by the genetic susceptibility of the host and intrinsic alterations in mucosal barrier function. In this review, we will describe advances in the understanding of how the interaction of host genetics and the intestinal microbiome contribute to the pathogenesis of IBD, with a focus on bacterial metabolites such as short chain fatty acids (SCFAs) as possible key signaling molecules.  In particular, we will describe alterations of the intestinal microbiota in IBD, focusing on how genetic loci affect the gut microbial phylogenetic distribution and the production of their major microbial metabolic product, SCFAs. We then describe how enteroendocrine cells and myenteric nerves express SCFA receptors that integrate networks such as the cholinergic and serotonergic neural systems and the glucagon-like peptide hormonal pathway, to modulate gut inflammation, permeability, and growth as part of an integrated model of IBD pathogenesis.  Through this integrative approach, we hope that novel hypotheses will emerge that will be tested in reductionist, hypothesis-driven studies in order to examine the interrelationship of these systems in the hope of better understanding IBD pathogenesis and to inform novel therapies.

scholarly journals Implication of Porphyromonas gingivalis in colitis and homeostasis of intestinal epithelium

2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Yoojin Seo ◽  
Su-Jeong Oh ◽  
Ji-Su Ahn ◽  
Ye Young Shin ◽  
Ji Won Yang ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Protective Effects ◽  
Intestinal Epithelial ◽  
Disease Symptoms ◽  
E Coli ◽  
Murine Colitis ◽  
Chemically Induced ◽  
Mouse Small Intestine ◽  
Colitis Model

AbstractEmerging evidences have reported that periodontitis can be a risk factor for the pathogenesis of various systemic diseases. Porphyromonas gingivalis (Pg), one of the crucial pathogens in chronic periodontitis, has been spotlighted as a potential cause for the promotion and acceleration of periodontitis-associated systemic disorders. To investigate the association between Pg and intestinal disease or homeostasis, we treated Pg-derived lipopolysaccharide (LPS) in murine colitis model or intestinal organoid, respectively. Pg-derived LPS (Pg LPS) was administrated into chemically induced murine colitis model and disease symptoms were monitored compared with the infusion of LPS derived from E. coli (Ec LPS). Organoids isolated and cultured from mouse small intestine were treated with Pg or Ec LPS and further analyzed for the generation and composition of organoids. In vivo observations demonstrated that both Pg and Ec LPS exerted slight protective effects against murine colitis. Pg LPS did not affect the generation and growth of intestinal epithelial organoids. Among subtypes of epithelial cells, markers for stem cells, goblet cells or Paneth cells were changed in response to Pg LPS. Taken together, these results indicate that Pg LPS leads to partial improvement in colitis and that its treatment does not significantly affect the self-organization of intestinal organoids but may regulate the epithelial composition.

scholarly journals Neutralization of IL-1α ameliorates Crohn’s disease-like ileitis by functional alterations of the gut microbiome

2019 ◽  
Vol 116 (52) ◽  
pp. 26717-26726 ◽  
Author(s):  
Paola Menghini ◽  
Daniele Corridoni ◽  
Ludovica F. Buttó ◽  
Abdullah Osme ◽  
Sushma Shivaswamy ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Intestinal Microbiome ◽  
Lactobacillus Salivarius ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Antiinflammatory Effects

Crohn’s disease and ulcerative colitis are chronic and progressive inflammatory bowel diseases (IBDs) that are attributed to dysregulated interactions between the gut microbiome and the intestinal mucosa-associated immune system. There are limited studies investigating the role of either IL-1α or IL-1β in mouse models of colitis, and no clinical trials blocking either IL-1 have yet to be performed. In the present study, we show that neutralization of IL-1α by a specific monoclonal antibody against murine IL-1α was highly effective in reducing inflammation and damage in SAMP mice, mice that spontaneously develop a Crohn’s-like ileitis. Anti-mouse IL-1α significantly ameliorated the established, chronic ileitis and also protected mice from developing acute DSS-induced colitis. Both were associated with taxonomic divergence of the fecal gut microbiome, which was treatment-specific and not dependent on inflammation. Anti–IL-1α administration led to a decreased ratio ofProteobacteriatoBacteroidetes, decreased presence ofHelicobacterspecies, and elevated representation ofMucispirillum schaedleriandLactobacillus salivarius. Such modification in flora was functionally linked to the antiinflammatory effects of IL-1α neutralization, as blockade of IL-1α was not effective in germfree SAMP mice. Furthermore, preemptive dexamethasone treatment of DSS-challenged SAMP mice led to changes in flora composition without preventing the development of colitis. Thus, neutralization of IL-1α changes specific bacterial species of the intestinal microbiome, which is linked to its antiinflammatory effects. These functional findings may be of significant value for patients with IBD, who may benefit from targeted IL-1α–based therapies.

scholarly journals Nutritional Therapies and Their Influence on the Intestinal Microbiome in Pediatric Inflammatory Bowel Disease

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 4
Author(s):  
Lara Hart ◽  
Charlotte M. Verburgt ◽  
Eytan Wine ◽  
Mary Zachos ◽  
Alisha Poppen ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Gut Microbiome ◽  
Low Cost ◽  
Autoimmune Disorder ◽  
Nutritional Therapy ◽  
Intestinal Microbiome ◽  
Microbial Composition ◽  
Inflammatory Bowel ◽  
And Function

Inflammatory bowel disease (IBD) is a chronic, autoimmune disorder of the gastrointestinal tract with numerous genetic and environmental risk factors. Patients with Crohn’s disease (CD) or ulcerative colitis (UC) often demonstrate marked disruptions of their gut microbiome. The intestinal microbiota is strongly influenced by diet. The association between the increasing incidence of IBD worldwide and increased consumption of a westernized diet suggests host nutrition may influence the progression or treatment of IBD via the microbiome. Several nutritional therapies have been studied for the treatment of CD and UC. While their mechanisms of action are only partially understood, existing studies do suggest that diet-driven changes in microbial composition and function underlie the diverse mechanisms of nutritional therapy. Despite existing therapies for IBD focusing heavily on immune suppression, nutrition is an important treatment option due to its superior safety profile, potentially low cost, and benefits for growth and development. These benefits are increasingly important to patients. In this review, we will describe the clinical efficacy of the different nutritional therapies that have been described for the treatment of CD and UC. We will also describe the effects of each nutritional therapy on the gut microbiome and summarize the strength of the literature with recommendations for the practicing clinician.

scholarly journals Propionate Fermentative Genes of the Gut Microbiome Decrease in Inflammatory Bowel Disease

2021 ◽  
Vol 10 (10) ◽  
pp. 2176
Author(s):  
Juan Manuel Medina ◽  
Raúl Fernández-López ◽  
Javier Crespo ◽  
Fernando de la Cruz
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Species Abundance ◽  
Short Chain Fatty Acids ◽  
Protective Role ◽  
Genomic Diversity ◽  
Causal Mechanism ◽  
Inflammatory Bowel

Changes in the gut microbiome have been associated with inflammatory bowel disease. A protective role of short chain fatty acids produced by the gut microbiota has been suggested as a causal mechanism. Nevertheless, multi-omic analyses have failed to identify a clear link between changes in specific taxa and disease states. Recently, metagenomic analyses unveiled that gut bacterial species have a previously unappreciated genomic diversity, implying that a geno-centric approach may be better suited to identifying the mechanisms involved. Here, we quantify the abundance of terminal genes in propionate-producing fermentative pathways in the microbiome of a large cohort of healthy subjects and patients with inflammatory bowel disease. The results show that propionate kinases responsible for propionate production in the gut are depleted in patients with Crohn’s disease. Our results also indicate that changes in overall species abundances do not necessarily correlate with changes in the abundances of metabolic genes, suggesting that these genes are not part of the core genome. This, in turn, suggests that changes in strain composition may be as important as changes in species abundance in alterations of the gut microbiome associated with pathological conditions.

scholarly journals Systematic Review: The Gut Microbiome and Its Potential Clinical Application in Inflammatory Bowel Disease

2021 ◽  
Vol 9 (5) ◽  
pp. 977
Author(s):  
Laila Aldars-García ◽  
María Chaparro ◽  
Javier P. Gisbert
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Gut Microbiome ◽  
Pathogenic Bacteria ◽  
Intestinal Inflammation ◽  
Systemic Disease ◽  
Microbial Community Composition ◽  
Temporal Stability ◽  
Intestinal Microbiome ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic relapsing–remitting systemic disease of the gastrointestinal tract. It is well established that the gut microbiome has a profound impact on IBD pathogenesis. Our aim was to systematically review the literature on the IBD gut microbiome and its usefulness to provide microbiome-based biomarkers. A systematic search of the online bibliographic database PubMed from inception to August 2020 with screening in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. One-hundred and forty-four papers were eligible for inclusion. There was a wide heterogeneity in microbiome analysis methods or experimental design. The IBD intestinal microbiome was generally characterized by reduced species richness and diversity, and lower temporal stability, while changes in the gut microbiome seemed to play a pivotal role in determining the onset of IBD. Multiple studies have identified certain microbial taxa that are enriched or depleted in IBD, including bacteria, fungi, viruses, and archaea. The two main features in this sense are the decrease in beneficial bacteria and the increase in pathogenic bacteria. Significant differences were also present between remission and relapse IBD status. Shifts in gut microbial community composition and abundance have proven to be valuable as diagnostic biomarkers. The gut microbiome plays a major role in IBD, yet studies need to go from casualty to causality. Longitudinal designs including newly diagnosed treatment-naïve patients are needed to provide insights into the role of microbes in the onset of intestinal inflammation. A better understanding of the human gut microbiome could provide innovative targets for diagnosis, prognosis, treatment and even cure of this relevant disease.

scholarly journals Antibacterial Monoclonal Antibodies Do Not Disrupt the Intestinal Microbiome or Its Function

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Omari Jones-Nelson ◽  
Andrey Tovchigrechko ◽  
Matthew S. Glover ◽  
Fiona Fernandes ◽  
Udaya Rangaswamy ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Broad Spectrum ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Intestinal Microbiome ◽  
Bacterial Metabolites ◽  
Minimal Impact ◽  
Fecal Microbiome ◽  
Alpha And Beta Diversity ◽  
Broad Spectrum Antibiotics

ABSTRACT Antibiotics revolutionized the treatment of infectious diseases; however, it is now clear that broad-spectrum antibiotics alter the composition and function of the host’s microbiome. The microbiome plays a key role in human health, and its perturbation is increasingly recognized as contributing to many human diseases. Widespread broad-spectrum antibiotic use has also resulted in the emergence of multidrug-resistant pathogens, spurring the development of pathogen-specific strategies such as monoclonal antibodies (MAbs) to combat bacterial infection. Not only are pathogen-specific approaches not expected to induce resistance in nontargeted bacteria, but they are hypothesized to have minimal impact on the gut microbiome. Here, we compare the effects of antibiotics, pathogen-specific MAbs, and their controls (saline or control IgG [c-IgG]) on the gut microbiome of 7-week-old, female, C57BL/6 mice. The magnitude of change in taxonomic abundance, bacterial diversity, and bacterial metabolites, including short-chain fatty acids (SCFA) and bile acids in the fecal pellets from mice treated with pathogen-specific MAbs, was no different from that with animals treated with saline or an IgG control. Conversely, dramatic changes were observed in the relative abundance, as well as alpha and beta diversity, of the fecal microbiome and bacterial metabolites in the feces of all antibiotic-treated mice. Taken together, these results indicate that pathogen-specific MAbs do not alter the fecal microbiome like broad-spectrum antibiotics and may represent a safer, more-targeted approach to antibacterial therapy.

scholarly journals Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment: a randomized trial of preterm infants

2020 ◽  
Author(s):  
Jordan T. Russell ◽  
J. Lauren Ruoss ◽  
Diomel de la Cruz ◽  
Nan Li ◽  
Catalina Bazacliu ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Antibiotic Use ◽  
Intestinal Microbiome ◽  
Preterm Neonates ◽  
Gamma Aminobutyric Acid ◽  
Immune Markers ◽  
Microbiome Diversity ◽  
Infant Gut Microbiome ◽  
Stool Samples ◽  
To Receive

AbstractAntibiotic use in neonates can have detrimental effects on the developing gut microbiome, increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice. Here microbiome, metabolomic, and immune marker results from the Routine Early Antibiotic use in SymptOmatic preterm Neonates (REASON) study are presented. The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 hours after birth. Using 16S rRNA sequencing of stool samples collected longitudinally for 91 neonates, the effect of such antibiotic use on microbiome diversity is assessed. The results illustrate that type of nutrition shapes the early infant gut microbiome. By integrating data for the gut microbiome, stool metabolites, stool immune markers, and inferred metabolic pathways, an association was discovered between Veillonella and the neurotransmitter gamma-aminobutyric acid (GABA). These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development, a finding that needs to be validated in a larger cohort.

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