The Functional Role of Fecal Microbiota Transplantation on Dextran Sulfate Sodium-Induced Colitis in Mice

He, Yan; Li, Xueting; Yu, Hengyuan; Ge, Yixuan; Liu, Yuanli; Qin, Xiaofa; Jiang, Meng; Wang, Xiuhong

doi:10.3389/fcimb.2019.00393

Cited by 26 publications

(17 citation statements)

References 46 publications

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“…mice before and at the onset of colitis. 32 At variance with transfer of feces from untreated mice, the transplantation of feces from 3-IAld-treated mice prevented weight loss (figure 6A), and ameliorated colon histopathology (figure 6B-D) in DSS-treated mice and similarly in DSS +anti-CTLA-4-treated mice (figure 6E). The reduced colonic inflammation was accompanied by the induction of IL-10-producing regulatory T cells (Treg) (figure 6F), as revealed by the reversal of DNA hypermethylation of Foxp3 promoter, likely occurring via butyrate (figure 6F), as already shown.…”

Section: Open Accessmentioning

confidence: 94%

Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite

Renga

Nunzi

Pariano

et al. 2022

J Immunother Cancer

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BackgroundDespite the great success, the therapeutic benefits of immune checkpoint inhibitors (ICIs) in cancer immunotherapy are limited by either various resistance mechanisms or ICI-associated toxic effects including gastrointestinal toxicity. Thus, novel therapeutic strategies that provide manageable side effects to existing ICIs would enhance and expand their therapeutic efficacy and application. Due to its proven role in cancer development and immune regulation, gut microbiome has gained increasing expectation as a potential armamentarium to optimize immunotherapy with ICI. However, much has to be learned to fully harness gut microbiome for clinical applicability. Here we have assessed whether microbial metabolites working at the interface between microbes and the host immune system may optimize ICI therapy.MethodsTo this purpose, we have tested indole-3-carboxaldehyde (3-IAld), a microbial tryptophan catabolite known to contribute to epithelial barrier function and immune homeostasis in the gut via the aryl hydrocarbon receptor (AhR), in different murine models of ICI-induced colitis. Epithelial barrier integrity, inflammation and changes in gut microbiome composition and function were analyzed. AhR, indoleamine 2,3-dioxygenase 1, interleukin (IL)-10 and IL-22 knockout mice were used to investigate the mechanism of 3-IAld activity. The function of the microbiome changes induced by 3-IAld was evaluated on fecal microbiome transplantation (FMT). Finally, murine tumor models were used to assess the effect of 3-IAld treatment on the antitumor activity of ICI.ResultsOn administration to mice with ICI-induced colitis, 3-IAld protected mice from intestinal damage via a dual action on both the host and the microbes. Indeed, paralleling the activation of the host AhR/IL-22-dependent pathway, 3-IAld also affected the composition and function of the microbiota such that FMT from 3-IAld-treated mice protected against ICI-induced colitis with the contribution of butyrate-producing bacteria. Importantly, while preventing intestinal damage, 3-IAld did not impair the antitumor activity of ICI.ConclusionsThis study provides a proof-of-concept demonstration that moving past bacterial phylogeny and focusing on bacterial metabolome may lead to a new class of discrete molecules, and that working at the interface between microbes and the host immune system may optimize ICI therapy.

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Section: Open Accessmentioning

confidence: 94%

Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite

Renga

Nunzi

Pariano

et al. 2022

J Immunother Cancer

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“…Fecal microbial transplantation (FMT) was achieved as described previously (18)(19)(20). Briefly, C57BL/6J female mice (n = 40; weight, 20 ± 2g) were randomly divided into four groups: F-NC, F-Kae, F-DSS, and F-DSS-Kae, and each group was designated to receive daily fresh fecal supernatant from NC, Kae, DSS, and DSS-Kae group donors, respectively.…”

Section: Fecal Microbial Transplantation and Co-housing Experimentsmentioning

confidence: 99%

Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis

Yan

et al. 2021

Front. Immunol.

141

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Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)–dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.

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“…Therefore, FMT can be used to alleviate, treat, or prevent the occurrence and development of UC. The ability to improve intestinal barrier integrity may be an important factor for effective FMT treatment [71] . In the future, detecting and analyzing a suitable treatment time and frequency of FMT or exploring more targeted treatments for dysbiosis may help to better guide the treatment of UC.…”

Section: Intestinal Bacteria Are Important Factors For the Development Of Uc And Dysbiosis Further Increases Susceptibility To Ucmentioning

confidence: 99%

MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis

et al. 2021

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The mucin2 (MUC2) mucus barrier acts as the first barrier that prevents direct contact between intestinal bacteria and colonic epithelial cells. Bacterial factors related to the MUC2 mucus barrier play important roles in the response to changes in dietary patterns, MUC2 mucus barrier dysfunction, contact stimulation with colonic epithelial cells, and mucosal and submucosal inflammation during the occurrence and development of ulcerative colitis (UC). In this review, these underlying mechanisms are summarized and updated, and related interventions for treating UC, such as dietary adjustment, exogenous repair of the mucus barrier, microbiota transplantation and targeted elimination of pathogenic bacteria, are suggested. Such interventions are likely to induce and maintain a long and stable remission period and reduce or even avoid the recurrence of UC. A better mechanistic understanding of the MUC2 mucus barrier and its related bacterial factors may help researchers and clinicians to develop novel approaches for treating UC.

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The Functional Role of Fecal Microbiota Transplantation on Dextran Sulfate Sodium-Induced Colitis in Mice

Cited by 26 publications

References 46 publications

Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite

Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite

Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis

MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis

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