Role of TRPV1 in colonic mucin production and gut microbiota profile

Kumar, Vijay; Mahajan, Neha; Khare, Pragyanshu; Kondepudi, Kanthi Kiran; Bishnoi, Mahendra

doi:10.1101/2020.04.17.046011

Cited by 4 publications

(5 citation statements)

References 66 publications

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“…A reduced α-diversity was reported in KO mice, when compared to wild-type (WT) counterparts, as well as a β-diversity change by clustering several gut microbiota populations. At the phylum level, the Firmicutes/Bacteroidetes ratio diminished in KO mice, by reducing Firmicutes and enhancing Bacteroidetes abundance [100,101]. Moreover, ablation of TRPV1 neurons by the potent agonist resiniferatoxin induced a severe mucus level reduction, caused by the downregulation of multiple associated genes, and a reduction in the abundance of lactic acid-producing bacteria [101].…”

Section: Modulation Of the Gut Microbiota By Capsaicinmentioning

confidence: 99%

“…At the phylum level, the Firmicutes/Bacteroidetes ratio diminished in KO mice, by reducing Firmicutes and enhancing Bacteroidetes abundance [100,101]. Moreover, ablation of TRPV1 neurons by the potent agonist resiniferatoxin induced a severe mucus level reduction, caused by the downregulation of multiple associated genes, and a reduction in the abundance of lactic acid-producing bacteria [101]. Thus, TRPV1 may be essential for proper mucin production and for the preservation of a healthy gut bacterial population.…”

Section: Modulation Of the Gut Microbiota By Capsaicinmentioning

confidence: 99%

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Capsaicin and Gut Microbiota in Health and Disease

et al. 2020

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Capsaicin is a widespread spice known for its analgesic qualities. Although a comprehensive body of evidence suggests pleiotropic benefits of capsaicin, including anti-inflammatory, antioxidant, anti-proliferative, metabolic, or cardioprotective effects, it is frequently avoided due to reported digestive side-effects. As the gut bacterial profile is strongly linked to diet and capsaicin displays modulatory effects on gut microbiota, a new hypothesis has recently emerged about its possible applicability against widespread pathologies, such as metabolic and inflammatory diseases. The present review explores the capsaicin–microbiota crosstalk and capsaicin effect on dysbiosis, and illustrates the intimate mechanisms that underlie its action in preventing the onset or development of pathologies like obesity, diabetes, or inflammatory bowel diseases. A possible antimicrobial property of capsaicin, mediated by the beneficial alteration of microbiota, is also discussed. However, as data are coming mostly from experimental models, caution is needed in translating these findings to humans.

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Section: Modulation Of the Gut Microbiota By Capsaicinmentioning

confidence: 99%

Section: Modulation Of the Gut Microbiota By Capsaicinmentioning

confidence: 99%

Capsaicin and Gut Microbiota in Health and Disease

et al. 2020

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“…In one case, these beneficial and gut-microbiota-mediated effects of capsaicin were shown to be due to counteracting the CB1 overactivation by endocannabinoids in obesity [ 39 ]. However, in only a few of these experimental studies, the role of TRPV1, which is the major target for capsaicin, was investigated and demonstrated [ 41 ], despite the fact that also this ligand-activated channel is known to be strongly implicated in several aspects of energy metabolism control, ranging from food intake and satiety mechanisms to adipogenesis, white adipocyte browning and brown adipocyte activation [ 25 , 61 , 62 , 63 , 64 ]. In the present study, we assessed the effects of a 12 weeks dietary supplementation of CAE (equivalent to 4 mg capsaicinoids/day, of which 2.4 mg were capsaicin, 1.4 mg were dihydrocapsaicin and 0.2 mg were nordihydrocapsaicin) in reproductive-aged women with overweight and obesity undergoing a calorie-reduced diet (−500 kcal/day) on the gut microbiota and the expanded endocannabinoid system known as the eCBome.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, capsaicin modulates the gut microbiota population, which represents a critical factor for the anti-obesity effects that are exerted by this natural compound, contributing to improving glucose homeostasis through increasing short-chain fatty acids, regulating gastrointestinal hormones and inhibiting pro-inflammatory cytokines [ 39 , 40 ]. A very recent study suggested that such effects might be at least in part mediated by the activation of TRPV1 since the ablation of this ligand-activated channel from the rat intestine was found to cause gut dysbiosis, as evidenced by the decreased abundance of beneficial taxa and production of short-chain fatty acids, and by the impairment of colonic mucus secretion [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

Oral Capsaicinoid Administration Alters the Plasma Endocannabinoidome and Fecal Microbiota of Reproductive-Aged Women Living with Overweight and Obesity

et al. 2021

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Capsaicinoids, the pungent principles of chili peppers and prototypical activators of the transient receptor potential of the vanilloid type-1 (TRPV1) channel, which is a member of the expanded endocannabinoid system known as the endocannabinoidome (eCBome), counteract food intake and obesity. In this exploratory study, we examined the blood and stools from a subset of the participants in a cohort of reproductive-aged women with overweight/obesity who underwent a 12-week caloric restriction of 500 kcal/day with the administration of capsaicinoids (two capsules containing 100 mg of a capsicum annuum extract (CAE) each for a daily dose of 4 mg of capsaicinoids) or a placebo. Samples were collected immediately before and after the intervention, and plasma eCBome mediator levels (from 23 participants in total, 13 placebo and 10 CAE) and fecal microbiota taxa (from 15 participants in total, 9 placebo and 6 CAE) were profiled using LC–MS/MS and 16S metagenomic sequencing, respectively. CAE prevented the reduced caloric-intake-induced decrease in beneficial eCBome mediators, i.e., the TRPV1, GPR119 and/or PPARα agonists, N-oleoyl-ethanolamine, N-linoleoyl-ethanolamine and 2-oleoyl-glycerol, as well as the anti-inflammatory N-acyl-ethanolamines N-docosapentaenyl-ethanolamine and N-docosahexaenoyl-ethanolamine. CAE produced few but important alterations in the fecal microbiota, such as an increased relative abundance of the genus Flavonifractor, which is known to be inversely associated with obesity. Correlations between eCBome mediators and other potentially beneficial taxa were also observed, thus reinforcing the hypothesis of the existence of a link between the eCBome and the gut microbiome in obesity.

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“…A recent study revealed that TRPA1 agonist cinnamaldehyde induced HCO 3-secretion in colon, which is essential for mucus release 11 . Recently published work from our laboratory demonstrated that systemic TRPV1 ablation leads to impaired mucus secretion and causes dysbiosis in the gut 12 . Given the importance of TRPA1 and TRPV1 in gut mucin-immune axis, we hypothesize that the strategies of blocking (with antagonists) or desensitizing sensory nociceptive neuronal TRPV1 and TRPA1 for the treatment of IBD might impair colonic mucin homeostasis, leading to increased gut permeability and dysbiosis.…”

Section: Introductionmentioning

confidence: 99%

Colon Innervating TRPA1 Positive Nociceptors Influence Mucosal Health In Mice

Bishnoi¹,

Kumar²,

Devi³

et al. 2021

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Introduction: Transient receptor potential ankyrin-1 positive (TRPA1+ve) nociceptors, primarily present as peptidergic neuronal afferents in the colon are sensors of disturbance in lower gastrointestinal tract including pain induced by different pathologies. Their therapeutic role in the alleviation of chronic pain (receptor antagonism and receptor desensitization) associated with inflammatory bowel diseases (IBD) is reported. However, there is limited literature available about their role in formation and sustenance of the mucosal layer, and its interaction with host physiology as well as luminal microbial community. The aim of this study focuses on the effects of nociceptive TRPA1 channel desensitization on colonic mucus production and gut health. Methods: TRPA1+ve nociceptors were desensitized by rectal administration of capsazepine. Ileum, colon was harvested and cecum content was collected. We performed morphological/histological analysis, gut permeability alteration, gene expression changes, colon metabolite profiling, and gut microbial abundance in these animals. Results: We found that presence of TRPA1-positive nociceptors is required for mucus layer integrity, using an intra-rectal capsazepine-induced TRPA1 desensitization model. Desensitization of TRPA1 positive nociceptors resulted in damaged mucosal lining, resultant increase in gut permeability and altered transcriptional profile of genes for goblet cell markers, mucus regulation, immune response and tight junction proteins. The damage to mucosal lining prevented its role in enterosyne (short chain fatty acids) actions. Conclusion: These results suggest that caution may need to be exercised before employing TRPA1 desensitization as a therapeutic option to alleviate pain caused due to IBD.

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Role of TRPV1 in colonic mucin production and gut microbiota profile

Cited by 4 publications

References 66 publications

Capsaicin and Gut Microbiota in Health and Disease

Capsaicin and Gut Microbiota in Health and Disease

Oral Capsaicinoid Administration Alters the Plasma Endocannabinoidome and Fecal Microbiota of Reproductive-Aged Women Living with Overweight and Obesity

Colon Innervating TRPA1 Positive Nociceptors Influence Mucosal Health In Mice

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