Manipulation of epithelial integrity and mucosal immunity by host and microbiota‐derived metabolites

Kayama, Hisako

doi:10.1002/eji.201948478

Cited by 42 publications

(22 citation statements)

References 104 publications

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“…The difference in the gut microbiome is likely to be the major driving force behind therapeutic outcomes between oral and rectal deliveries of EGCG. Considering the modulation of epithelial integrity and mucosal immunity by the microbiota and microbiota-derived metabolites [58,59], and the correlation we have revealed here, we concluded that the gut microbiome induced by EGCG contributes to the homeostatic balance of colon. This conclusion is further supported by the fact that EGCG has a low bioavailability and is poorly absorbed by the GI tract and thus its direct impact on host physiology is believed to be rather limited [21].…”

Section: Discussionsupporting

confidence: 56%

Oral, but not rectal delivery of epigallocatechin-3-gallate alleviates colitis by regulating the gut microbiota, oxidative stress, inflammation, and barrier integrity

Huang

et al. 2020

Preprint

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Background: Alteration of the gut microbiota may contribute to the development of inflammatory bowel diseases (IBDs). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBDs alleviation. However, it is unclear whether EGCG attenuates IBDs through direct improvement of gastrointestinal function or indirect alteration of the structure and function of the gut microbiota.Results: We first investigated the therapeutic effects of EGCG on disease severity, oxidative stress, inflammation, barrier function, and gut microbiota in murine colitis model, and further demonstrate it via EGCG pre-supplementation. We revealed that, oral, but not rectal, delivery of EGCG alleviated the severity of colitis through attenuation of anti-oxidative and anti-inflammatory response. Mucin-secreting goblet cell number, barrier function gene expression levels, and the integrity of tight junctions in the colon were also enhanced by oral EGCG. Additionally, we observed distinct EGCG-mediated alternation in the gut microbiome, as highlighted by increased Akkermansia abundance and butyrate production. Furthermore, we revealed that prophylactic oral application of EGCG for 21 days prior to the onset of dextran sodium sulfate (DSS)-induced colitis also ameliorated colonic damage, oxidative stress, and inflammatory response. Prophylactic EGCG significantly enriched Akkermansia, Faecalibaculum, and Bifidobacterium and enhanced acetate, propionate and butyrate production in DSS-treated mice. Moreover, scores of differential microbes, in particular Akkermansia, showed a strong positive correlation with short-chain fatty acids (SCFAs) and antioxidant enzyme levels in both the plasma and colon, but a negative association with inflammatory cytokines and malondialdehyde.Conclusions: EGCG is capable of treating DSS-induced colitis both therapeutically and prophylactically by inducing a pronounced anti-oxidative and anti-inflammatory response. Attenuation of colitis by oral, but not rectal administration of, EGCG suggests an intimate involvement of the gut microbiota. Increased Akkermansia and subsequent protective SCFAs production may be largely responsible for the anti-inflammatory and anti-oxidative function of EGCG, leading to restoration of intestinal epithelial homeostasis of the host. These findings provide novel insights into EGCG-mediated remission of IBDs and the rationale for devising more effective therapeutic strategies for IBDs.

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Section: Discussionsupporting

confidence: 56%

Oral, but not rectal delivery of epigallocatechin-3-gallate alleviates colitis by regulating the gut microbiota, oxidative stress, inflammation, and barrier integrity

Huang

et al. 2020

Preprint

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“…Collectively, our results suggested that EGCG-mediated microbial community, especially the enrichment of Akkermansia played a key role in the alleviation of colitis, which could be the major driving force behind reversal outcomes between oral and rectal deliveries of EGCG. These increased populations of SCFAs-producing microbes and their metabolites induced by EGCG delivery might also be involved in maintaining the homeostatic balance in the colon by improving the colonic epithelial integrity and mucosal immunity [65,66]. These results are summarized in Fig.…”

Section: Discussionmentioning

confidence: 94%

Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis

et al. 2021

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Background Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD. Results We first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT. Conclusions This study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD.

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“…including Kyn, XA and CA, are the ligands at the aryl hydrocarbon receptor (AHR), a transcription factor that regulates the maturation of different immune cells, epithelial renewal, and barrier integrity, thereby contributing to mucosal homeostasis 21,42,[46][47][48] . However, the mechanism of the regulation of Per1 and mosquitoes might present novel strategies for mosquito control.…”

Section: Discussionmentioning

confidence: 99%

“…Serotonin that functions as a neurohormone in mosquitoes modulates insulin-like peptides expression 13 , ion transportation 14 , feeding behavior 15 , salivation 16 and heart rate 17 . In mammalians, tryptophan and its metabolites are also key mediators that regulate immune responses and gut barrier function, thereby affecting hosts' susceptibility to pathogen infections [18][19][20][21][22][23] . However, little is known about the influence of mosquito tryptophan metabolism on pathogen transmission.…”

Section: Introductionmentioning

confidence: 99%

“…Our finding is generally consistent with the mammalian models demonstrating that gut microbiota influences intestinal homeostasis by participating kynurenine pathway19,42 . A variety of kynurenine metabolites, including Kyn, XA and CA, are the ligands at the aryl hydrocarbon receptor (AHR), a transcription factor that regulates the maturation of different immune cells, epithelial renewal, and barrier integrity, thereby contributing to mucosal homeostasis21,42,[46][47][48] . However, the mechanism of the regulation of Per1 expression by 3-HK remains unclear.…”

mentioning

confidence: 99%

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Microbial tryptophan catabolism affects the vector competence ofAnopheles

Feng

Peng

Wen

et al. 2021

Preprint

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The influence of microbiota on mosquito physiology and vector competence is becoming increasingly clear but our understanding of interactions between microbiota and mosquitoes still remains incomplete. Here we show that gut microbiota of Anopheles stephensi, a competent malaria vector, participates mosquito tryptophan metabolism. Elimination of microbiota by antibiotics treatment leads to the accumulation of tryptophan (Trp) and its metabolites, kynurenine (Kyn), 3-hydroxykynurenine (3-HK) and xanthurenic acid (XA). Of these, 3-HK impairs the structure of peritrophic matrix (PM), thereby promoting Plasmodium berghei infection. Among the major gut microbiota in An. stephensi, Pseudomonas alcaligenes plays a role in catabolizing 3-HK as revealed by whole genome sequencing and LC-MS metabolic analysis. The genome of P. alcaligenes encodes kynureninase (KynU) that is responsible for the conversion of 3-HK to 3-Hydroxyanthranilic acid (3-HAA). Mutation of this gene abrogates the ability of P. alcaligenes to metabolize 3-HK, which in turn abolishes its role on PM protection. Colonization of An. stephensi with KynU mutated P. alcaligenes fails to protect mosquitoes against parasite infection as effectively as those with wild type bacterium. In summary, we identify an unexpected function of gut microbiota in controlling mosquito tryptophan metabolism with the major consequences on vector competence.

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Manipulation of epithelial integrity and mucosal immunity by host and microbiota‐derived metabolites

Cited by 42 publications

References 104 publications

Oral, but not rectal delivery of epigallocatechin-3-gallate alleviates colitis by regulating the gut microbiota, oxidative stress, inflammation, and barrier integrity

Oral, but not rectal delivery of epigallocatechin-3-gallate alleviates colitis by regulating the gut microbiota, oxidative stress, inflammation, and barrier integrity

Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis

Microbial tryptophan catabolism affects the vector competence ofAnopheles

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