Depletion of dietary aryl hydrocarbon receptor ligands alters microbiota composition and function

Brawner, Kyle M.; Yeramilli, Venkata A.; Duck, L. Wayne; Pol, William Van Der; Smythies, Lesley E.; Morrow, Casey D.; Elson, Charles O.; Martin, Colin

doi:10.1038/s41598-019-51194-w

Cited by 43 publications

(37 citation statements)

References 57 publications

(67 reference statements)

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“…33 Our results suggest that indole or its derivatives are, in some measure, responsible for the rescue of the anxiety-like behavior in our model. We observed previously reported indole negative associations in taxa such as Erysipelotrichaceae 24 in IBS+A mice that were restored by S. bou. Moreover, predicted metabolomic profile indicated that IBS+A mice treated with S. bou had indeed higher number of bacterial genes implicated in indole alkaloid biosynthesis compared with IBS+A mice receiving water ( Figure 5A), also suggesting higher indole levels.…”

Section: Discussionmentioning

confidence: 63%

“…Taxa expanded in IBS+A mice and decreased by S. bou, such as Erysipelotrichaceae, have been shown to be affected by dietary indole levels. 24 PICRUSt analysis indicated that IBS+A mice treated with S. bou had over 20-fold (p = 0.01) higher number of bacterial genes implicated in indole alkaloid biosynthesis compared with IBS+A mice receiving water ( Figure 5A), suggesting higher levels of indole.…”

Section: S Bou Increases Microbial Indole Production In Vitromentioning

confidence: 99%

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Saccharomyces boulardii CNCM I‐745 modulates the microbiota–gut–brain axis in a humanized mouse model of Irritable Bowel Syndrome

Constante

Palma

Lü

et al. 2020

Neurogastroenterology Motil

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Background: Gnotobiotic mice colonized with microbiota from patients with irritable bowel syndrome (IBS) and comorbid anxiety (IBS+A) display gut dysfunction and anxiety-like behavior compared to mice colonized with microbiota from healthy volunteers. Using this model, we tested the therapeutic potential of the probiotic yeast Saccharomyces boulardii strain CNCM I-745 (S. bou) and investigated underlying mechanisms. Methods: Germ-free Swiss Webster mice were colonized with fecal microbiota from an IBS+A patient or a healthy control (HC). Three weeks later, mice were gavaged daily with S. boulardii or placebo for two weeks. Anxiety-like behavior (light preference and step-down tests), gastrointestinal transit, and permeability were assessed. After sacrifice, samples were taken for gene expression by NanoString and qRT-PCR, microbiota 16S rRNA profiling, and indole quantification. Key Results: Mice colonized with IBS+A microbiota developed faster gastrointestinal transit and anxiety-like behavior (longer step-down latency) compared to mice with HC microbiota. S. bou administration normalized gastrointestinal transit and anxiety-like behavior in mice with IBS+A microbiota. Step-down latency correlated with colonic Trpv1 expression and was associated with altered microbiota profile and increased Indole-3-acetic acid (IAA) levels. Conclusions & Inferences: Treatment with S. bou improves gastrointestinal motility and anxiety-like behavior in mice with IBS+A microbiota. Putative mechanisms include effects on pain pathways, direct modulation of the microbiota, and indole production by commensal bacteria.

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Section: Discussionmentioning

confidence: 63%

Section: S Bou Increases Microbial Indole Production In Vitromentioning

confidence: 99%

Saccharomyces boulardii CNCM I‐745 modulates the microbiota–gut–brain axis in a humanized mouse model of Irritable Bowel Syndrome

Constante

Palma

Lü

et al. 2020

Neurogastroenterology Motil

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“…AHR ligands include tryptophan metabolites derived from microbiota and dietary macronutrients. The activation of the AHR signaling pathway is important for maintaining gut health including a direct effect on mucosal immunity [74]. For example, intestinal AHR signaling is important for intestinal crypt stem cell differentiation [75].…”

Section: Polyamines Ahr Ligands and Gut Homeostasismentioning

confidence: 99%

The Role of the Microbiome in Food Allergy: A Review

et al. 2020

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Food allergies are common and estimated to affect 8% of children and 11% of adults in the United States. They pose a significant burden—physical, economic and social—to those affected. There is currently no available cure for food allergies. Emerging evidence suggests that the microbiome contributes to the development and manifestations of atopic disease. According to the hygiene hypothesis, children growing up with older siblings have a lower incidence of allergic disease compared with children from smaller families, due to their early exposure to microbes in the home. Research has also demonstrated that certain environmental exposures, such as a farming environment, during early life are associated with a diverse bacterial experience and reduced risk of allergic sensitization. Dysregulation in the homeostatic interaction between the host and the microbiome or gut dysbiosis appears to precede the development of food allergy, and the timing of such dysbiosis is critical. The microbiome affects food tolerance via the secretion of microbial metabolites (e.g., short chain fatty acids) and the expression of microbial cellular components. Understanding the biology of the microbiome and how it interacts with the host to maintain gut homeostasis is helpful in developing smarter therapeutic approaches. There are ongoing trials evaluating the benefits of probiotics and prebiotics, for the prevention and treatment of atopic diseases to correct the dysbiosis. However, the routine use of probiotics as an intervention for preventing allergic disease is not currently recommended. A new approach in microbial intervention is to attempt a more general modification of the gut microbiome, such as with fecal microbiota transplantation. Developing targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy. Similarly, fecal microbiota transplantation is being explored as a potentially beneficial interventional approach. Overall, targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy.

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“…In comparison to the diverse microbiota of mice reared on conventional grain-based chow, the immune phenotype of the microbiome of mice fed purified, phytochemical-free diets (often termed AHR ligand-free diets) is changed in a manner similar to that seen in AHR-deficient animals [ 28 , 112 , 113 ]. Like the AHR-deficient mice, animals fed purified, phytochemical-free diets exhibit enhanced susceptibility to severe colitis [ 113 , 114 , 115 ].…”

Section: The Mechanism(s) By Which Ficz Il-22 and Butyrate Promotmentioning

confidence: 99%

How the AHR Became Important in Intestinal Homeostasis—A Diurnal FICZ/AHR/CYP1A1 Feedback Controls Both Immunity and Immunopathology

Rannug

2020

IJMS

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Ever since the 1970s, when profound immunosuppression caused by exogenous dioxin-like compounds was first observed, the involvement of the aryl hydrocarbon receptor (AHR) in immunomodulation has been the focus of considerable research interest. Today it is established that activation of this receptor by its high-affinity endogenous ligand, 6-formylindolo[3,2-b]carbazole (FICZ), plays important physiological roles in maintaining epithelial barriers. In the gut lumen, the small amounts of FICZ that are produced from L-tryptophan by microbes are normally degraded rapidly by the inducible cytochrome P4501A1 (CYP1A1) enzyme. This review describes how when the metabolic clearance of FICZ is attenuated by inhibition of CYP1A1, this compound passes through the intestinal epithelium to immune cells in the lamina propria. FICZ, the level of which is thus modulated by this autoregulatory loop involving FICZ itself, the AHR and CYP1A1, plays a central role in maintaining gut homeostasis by potently up-regulating the expression of interleukin 22 (IL-22) by group 3 innate lymphoid cells (ILC3s). IL-22 stimulates various epithelial cells to produce antimicrobial peptides and mucus, thereby both strengthening the epithelial barrier against pathogenic microbes and promoting colonization by beneficial bacteria. Dietary phytochemicals stimulate this process by inhibiting CYP1A1 and causing changes in the composition of the intestinal microbiota. The activity of CYP1A1 can be increased by other microbial products, including the short-chain fatty acids, thereby accelerating clearance of FICZ. In particular, butyrate enhances both the level of the AHR and CYP1A1 activity by stimulating histone acetylation, a process involved in the daily cycle of the FICZ/AHR/CYP1A1 feedback loop. It is now of key interest to examine the potential involvement of FICZ, a major physiological activator of the AHR, in inflammatory disorders and autoimmunity.

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Depletion of dietary aryl hydrocarbon receptor ligands alters microbiota composition and function

Cited by 43 publications

References 57 publications

Saccharomyces boulardii CNCM I‐745 modulates the microbiota–gut–brain axis in a humanized mouse model of Irritable Bowel Syndrome

Saccharomyces boulardii CNCM I‐745 modulates the microbiota–gut–brain axis in a humanized mouse model of Irritable Bowel Syndrome

The Role of the Microbiome in Food Allergy: A Review

How the AHR Became Important in Intestinal Homeostasis—A Diurnal FICZ/AHR/CYP1A1 Feedback Controls Both Immunity and Immunopathology

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