Microbiota‐derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo

Jennis, Matthew; Cavanaugh, Cassandre R.; Leo, Gregory C.; Mabus, John R.; Lenhard, James M.; Hornby, Pamela J.

doi:10.1111/nmo.13178

Cited by 131 publications

(114 citation statements)

References 42 publications

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“…This metabolite and related bacterial compounds (indole-3-aldehyde, indole-3-lactate, and indole-3-propionate) were previously shown to reduce intestinal inflammation and to prevent gut barrier dysfunction (19, 25, 26, 35–38). In the present study, we show for the first time that indole alleviates inflammation in the liver, away from the gut.…”

Section: Discussionmentioning

confidence: 99%

The gut microbiota metabolite indole alleviates liver inflammation in mice

et al. 2018

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The gut microbiota regulates key hepatic functions, notably through the production of bacterial metabolites that are transported via the portal circulation. We evaluated the effects of metabolites produced by the gut microbiota from aromatic amino acids (phenylacetate, benzoate, p-cresol, and indole) on liver inflammation induced by bacterial endotoxin. Precision-cut liver slices prepared from control mice, Kupffer cell (KC)-depleted mice, and obese mice (ob/ob) were treated with or without LPS and bacterial metabolites. We observed beneficial effects of indole that dose-dependently reduced the LPS-induced up-regulation of proinflammatory mediators at both mRNA and protein levels in precision-cut liver slices prepared from control or ob/ob mice. KC depletion partly prevented the antiinflammatory effects of indole, notably through a reduction of nucleotide-binding domain and leucine-rich repeat containing (NLR) family pyrin domain-containing 3 (NLRP3) pathway activation. In vivo, the oral administration of indole before an LPS injection reduced the expression of key proteins of the NF-κB pathway and downstream proinflammatory gene up-regulation. Indole also prevented LPS-induced alterations of cholesterol metabolism through a transcriptional regulation associated with increased 4β-hydroxycholesterol hepatic levels. In summary, indole appears as a bacterial metabolite produced from tryptophan that is able to counteract the detrimental effects of LPS in the liver. Indole could be a new target to develop innovative strategies to decrease hepatic inflammation.—Beaumont, M., Neyrinck, A. M., Olivares, M., Rodriguez, J., de Rocca Serra, A., Roumain, M., Bindels, L. B., Cani, P. D., Evenepoel, P., Muccioli, G. G., Demoulin, J.-B., Delzenne, N. M. The gut microbiota metabolite indole alleviates liver inflammation in mice.

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Section: Discussionmentioning

confidence: 99%

The gut microbiota metabolite indole alleviates liver inflammation in mice

et al. 2018

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“…Plasma IPA amounts were also reported to increase in the same obese model 3 months after Roux-en-Y gastric bypass (RYGB) surgery 64 , indicating, once again, the direct involvement of gut microbiota in the maintenance of the intestinal barrier functions. Furthermore, results from in vitro assays reported by the same authors showed that IPA could reduce the permeability of T84 cell monolayer compromised by pro-inflammatory cytokines 64 .…”

Section: The Role Of Microbiota and Microbiota-derived Dietary Metabomentioning

confidence: 89%

Exploring the Molecular Pathways Behind the Effects of Nutrients and Dietary Polyphenols on Gut Microbiota and Intestinal Permeability: A Perspective on the Potential of Metabolomics and Future Clinical Applications

Peron

Hidalgo‐Liberona

González‐Domínguez

et al. 2019

J. Agric. Food Chem.

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The gastrointestinal tract hosts the largest microbial population of the human body, which works in symbiosis with the host to provide several important functions and contributes to the maintenance of host health. The diet is one of the factors that can most affect the gut microbiota, with subsequent consequences on host health. One consequence of changes in microbiota is changes in intestinal permeability (IP); disruption of this latter is related to the development of several diseases and is a frequent condition in older people. Nevertheless, the molecular pathways regulating these effects are still unclear, and a comprehensive understanding of the dietary components that can affect IP is lacking. Metabolomics, that has been widely used to study the transformation of nutrients by intestinal microbiota, could be a suitable approach for this purpose. However, up to now, the research has focused mainly on dietary fibers and tryptophan, while the activity of dietary polyphenols remains almost completely unexplored. Hence, the aim here was to review the most recent literature concerning the application of metabolomics in the study of the correlation between diet-induced alterations of gut microbiota and the effects on intestinal permeability, with a particular focus on the discovery of the molecular pathways involved. An additional aim was to give a perspective on the future research involving dietary polyphenols, given that despite their potential implication for the prevention and treatment of several diseases related to increased intestinal permeability, few studies have been reported to date.

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“…Jennis et al . have identified an important role for gut microbiome‐derived tryptophan metabolites, especially IPA, for gut health.…”

Section: Discussionmentioning

confidence: 99%

“…Jennis et al ,. in this issue tested the hypothesis that tryptophan metabolites produced by gut bacteria could reduce intestinal inflammation in high fat diet (HFD) fed mice, in lean human and in obese T2D human patients undergoing Roux‐en‐Y gastric by‐pass surgery for weight loss.…”

Section: Obesity the Gut Microbiome And Tryptophan Metabolismmentioning

confidence: 99%

“…While host metabolism is the main pathway for tryptophan metabolism, the microbiota also produces benefical metabolites. IDO1 is a host enzyme that metabolizes tryptophan to kynurenine . The role of IDO1 and tryptophan metabolism by the host and the microbiota in maintaining gut mucosal homeostasis was studied in wild type and in IDO −/− mice .…”

Section: Host Genetics Obesity Microbiome and Gut Healthmentioning

confidence: 99%

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Beneficial actions of microbiota‐derived tryptophan metabolites

Galligan

2018

Neurogastroenterology Motil

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Tryptophan is an important dietary amino acid and it is the precursor for 5-hydroxytryptamine synthesis in the nervous system and by enterochromaffin cells in the gut mucosa. Tryptophan is also metabolized by enzymes in the gut mucosa and also by enzymes produced by the gut microbiome. Diet and the microbiome can contribute to metabolic disease in part by causing intestinal inflammation and increased permeability. In this issue of Neurogastroenterology and Motility, Jennis et al. test the hypothesis that indole tryptophan metabolites produced by gut bacteria might be responsible for the anti-inflammatory and beneficial metabolic effects of the gut microbiome and Roux-en-Y gastric bypass surgery for weight loss by obese patients. The authors identified indole-3-propionic acid as the beneficial metabolite. A review of the literature also revealed the beneficial effects of tryptophan metabolites on diabetes and metabolic disease and on inflammatory bowel disease. Taken together, these data highlight another health benefit of the intestinal microbiome, which produces beneficial products from dietary amino acids especially tryptophan.

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Microbiota‐derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo

Cited by 131 publications

References 42 publications

The gut microbiota metabolite indole alleviates liver inflammation in mice

The gut microbiota metabolite indole alleviates liver inflammation in mice

Exploring the Molecular Pathways Behind the Effects of Nutrients and Dietary Polyphenols on Gut Microbiota and Intestinal Permeability: A Perspective on the Potential of Metabolomics and Future Clinical Applications

Beneficial actions of microbiota‐derived tryptophan metabolites

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