Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages

Krishnan, Smitha; Ding, Yufang; Saedi, Nima; Choi, Maria; Sridharan, Gautham; Sherr, David H.; Yarmush, Martin L.; Alaniz, Robert C.; Jayaraman, Arul; Lee, Kyongbum

doi:10.1016/j.celrep.2018.03.109

Cited by 426 publications

(371 citation statements)

References 53 publications

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“…In the case of indole acetate production, the result shows that when such pathways score "High" in activity, the glycemic response to the given food is lower. This is consistent with known anti-inflammatory properties of IAA [Krishnan 2018]. Inflammatory activities in the gut and their consequential potential to cause systemic low-grade inflammation are implicated in the development of Type 2 Diabetes and other metabolic disorders [Gonzalez 2018;Tuomainen 2018].…”

Section: Relationships Between Iauc and Microbiome Featuressupporting

confidence: 85%

Gut microbiome activity contributes to individual variation in glycemic response in adults

Tily¹,

Perlina²,

Patridge³

et al. 2019

Preprint

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Limiting post-meal glycemic response is an important factor in reducing the risk of chronic metabolic diseases, and contributes to significant health benefits in people with elevated levels of blood sugar. In this study, we collected gut microbiome activity (i.e., metatranscriptomic) data and measured the glycemic responses of 550 adults who consumed more than 27,000 meals from omnivore or vegetarian/gluten-free diets. We demonstrate that gut microbiome activity makes a statistically significant contribution to individual variation in glycemic response, in addition to anthropometric factors and the nutritional composition of foods. We describe a predictive model (multilevel mixed-effects regression) of variation in glycemic response among individuals ingesting the same foods. We introduce functional features aggregated from microbial activity data as candidates for association with mechanisms of glycemic control. In summary, we demonstrate for the first time that metatranscriptomic activity of the gut microbiome is correlated with glycemic response among adults. Figure 1, we recruited 550 adults (~66% female), and tracked their food intake, sleep, activity, and glycemic response for up to 2 weeks. 400 participants were Caucasian, and of the remaining 150 participants, 37% were Asian, 33% were Hispanic, and 30% were *This study was performed while all authors were at Viome Inc. METHODS As described in

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Section: Relationships Between Iauc and Microbiome Featuressupporting

confidence: 85%

Gut microbiome activity contributes to individual variation in glycemic response in adults

Tily¹,

Perlina²,

Patridge³

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…(66,(73)(74)(75)(76)(77)(78)(109)(110)(111) The liver is exposed to commensal gut microbiota-derived ligands/metabolites through the portal venous circulation. (112)(113)(114) DCs are critical in presenting antigens to promote T-cell activation in liver-draining lymph nodes. (91) Our findings of elevated pDCs, T H 17 cells, and T H 1 cells in the LLNs of MPF mice suggest that SFB colonization drives hepatic innate immune responses leading to increased proinflammatory T H 17 cells and T H 1 cells in liver-draining lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

et al. 2020

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The commensal gut microbiota critically regulates immunomodulatory processes that influence normal skeletal growth and maturation. However, the influence of specific microbes on commensal gut microbiota osteoimmunoregulatory actions is unknown. We have shown previously that the commensal gut microbiota enhances TH17/IL17A immune response effects in marrow and liver that have procatabolic/antianabolic actions in the skeleton. Segmented filamentous bacteria (SFB), a specific commensal gut bacterium within phylum Firmicutes, potently induces TH17/IL17A‐mediated immunity. The study purpose was to delineate the influence of SFB on commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal development. Two murine models were utilized: SFB‐monoassociated mice versus germ‐free (GF) mice and specific‐pathogen‐free (SPF) mice +/− SFB. SFB colonization was validated by 16S rDNA analysis, and SFB‐induced TH17/IL17A immunity was confirmed by upregulation of Il17a in ileum and IL17A in serum. SFB‐colonized mice had an osteopenic trabecular bone phenotype, which was attributed to SFB actions suppressing osteoblastogenesis and enhancing osteoclastogenesis. Intriguingly, SFB‐colonized mice had increased expression of proinflammatory chemokines and acute‐phase reactants in the liver. Lipocalin‐2 (LCN2), an acute‐phase reactant and antimicrobial peptide, was substantially elevated in the liver and serum of SFB‐colonized mice, which supports the notion that SFB regulation of commensal gut microbiota osteoimmunomodulatory actions are mediated in part through a gut–liver–bone axis. Proinflammatory TH17 and TH1 cells were increased in liver‐draining lymph nodes of SFB‐colonized mice, which further substantiates that SFB osteoimmune‐response effects may be mediated through the liver. SFB‐induction of Il17a in the gut and Lcn2 in the liver resulted in increased circulating levels of IL17A and LCN2. Recognizing that IL17A and LCN2 support osteoclastogenesis/suppress osteoblastogenesis, SFB actions impairing postpubertal skeletal development appear to be mediated through immunomodulatory effects in both the gut and liver. This research reveals that specific microbes critically impact commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal growth and maturation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…[ 180 ] It is also possible that the reduced energy availability in the elderly favors an enrichment of tryptophan metabolizing gut microbes, since indole production is inversely proportional to host energy status. [ 181–183 ] This speculation, however, calls for further examination.…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

“…In rats, for instance, cecal indole concentration is elevated during fasting. Moreover, glucose inhibits indole production, and high‐fat diet depletes the microbial metabolites indole‐3‐acetate and tryptamine, [ 181–183 ] suggesting a reverse correlation between indole production and energy availability. Last, intestinal stem cell proliferation is linked to the host's energy state.…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

2020

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Microorganisms that colonize the gastrointestinal tract, collectively known as the gut microbiota, are known to produce small molecules and metabolites that significantly contribute to host intestinal development, functions, and homeostasis. Emerging insights from microbiome research reveal that gut microbiota‐derived signals and molecules influence another key player maintaining intestinal homeostasis—the intestinal stem cell niche, which regulates epithelial self‐renewal. In this review, the literature on gut microbiota‐host crosstalk is surveyed, highlighting the effects of gut microbial metabolites on intestinal stem cells. The production of various classes of metabolites, their actions on intestinal stem cells are discussed and, finally, how the production and function of metabolites are modulated by aging and dietary intake is commented upon.

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Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages

Cited by 426 publications

References 53 publications

Gut microbiome activity contributes to individual variation in glycemic response in adults

Gut microbiome activity contributes to individual variation in glycemic response in adults

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

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