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Roseburia intestinalis supernatant ameliorates colitis induced in mice by regulating the immune response.

ABSTRACT: Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), has a complex etiology that may be associated with dysbiosis of the microbiota. Previously, our study revealed significant loss of Roseburia intestinalis from the gut of untreated patients with CD, and that R. intestinalis exerted anti‑inflammatory functions in TNBS‑induced colitis; however, the function of R. intestinalis supernatant is unknown. Therefore, LPS‑induced macrophages, including RAW264.7 macrophages and bone marrow‑derived macrophages were treated with R. intestinalis supernatant. The results indicated that R. intestinalis supernatant suppressed expression of interleukin (IL)‑6 and signal transducer and activator of transcription 3 (STAT3) by macrophages. Additionally, these findings were further verified in vivo in DSS‑ and TNBS‑induced mouse models of colitis. It was observed that R. intestinalis supernatant ameliorated IBD colitis by reducing the number of inflammatory macrophages and Th17 cells in the colon, and by downregulating the expression of IL‑6 and STAT3. Finally, the non‑protein components of R. intestinalis supernatant were examined using gas chromatography‑mass spectrometry analysis and identified the presence of short‑chain fatty acids. In conclusion, the results of the present study indicated that R. intestinalis supernatant may regulate immune responses and ameliorate colitis.

SUBMITTER: Luo W

PROVIDER: S-EPMC6625378 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Roseburia intestinalis supernatant ameliorates colitis induced in mice by regulating the immune response.

Luo Weiwei W Shen Zhaohua Z Deng Minzi M Li Xiayu X Tan Bei B Xiao Mengwei M Wu Shuai S Yang Zhenyu Z Zhu Changxin C Tian Li L Wu Xing X Meng Xiangrui X Quan Yongsheng Y Wang Xiaoyan X

Molecular medicine reports 20190604 2

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), has a complex etiology that may be associated with dysbiosis of the microbiota. Previously, our study revealed significant loss of Roseburia intestinalis from the gut of untreated patients with CD, and that R. intestinalis exerted anti‑inflammatory functions in TNBS‑induced colitis; however, the function of R. intestinalis supernatant is unknown. Therefore, LPS‑induced macrophages, including RAW264 ...[more]

PMID: 31173202

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Project description:Some biologically active compounds isolated from sea cucumbers stimulate the body's immune response by activating immune cells. Immune function is closely related to the integrity intestinal barrier and balanced gut microbiota. However, it is unknown whether the daily administration of holothurian wall hydrolysate (HWH) ameliorated intestinal dysbiosis and barrier injury induced by immunodeficiency. This study aimed to investigate the immunomodulatory effect and the underlying mechanism of HWH in cyclophosphamide (CTX)-induced immunocompromised mice. BALB/c mice received CTX (80 mg/kg, intraperitoneally) once a day for 3 days to induce immunodeficiency, and then they received the oral administration of HWH (80 or 240 mg/kg) or levamisole hydrochloride (LH, 40 mg/kg, positive control), respectively, once a day for 7 days. We utilized 16S rRNA sequencing for microbial composition alterations, histopathological analysis for splenic and colonic morphology, Western blotting for expressions of tight junction proteins (TJs), and quantitative real-time (qRT)-PCR for measurements of pro-inflammatory cytokines. HWH attenuated the immune organ damage induced by CTX, increased the secretions of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, and promoted the recovery of goblet cells and the production of TJs (claudin-1, occludin, and ZO-1) in the colon of the immunocompromised mice. Moreover, HWH promoted the growth of beneficial microorganisms such as Lactobacillus, Lachnospiraceae, Christensenellaceae, and Bifidobacterium, while it suppressed the populations of Ruminococcus, Staphylococcus, and Streptococcus. These results demonstrate that HWH elicits intestinal mucosal immunity, repairs the damage to intestinal mucosal integrity, and normalizes the imbalanced intestinal microbial profiles in immunocompromised mice. It may be helpful to identify the biological activities of HWH to support its potential use in new prebiotics, immunomodulatory agents, and medical additives for intestinal repair.

Project description:BackgroundThe community of gut microbes is a key factor controlling the intestinal barrier that communicates with the nervous system through the gut-brain axis. Based on our clinical data showing that populations of Roseburia intestinalis are dramatically decreased in the gut of patients with ulcerative colitis, we studied the efficacy of a strain belonging to this species in the context of colitis and stress using animal models.MethodsDextran sulfate sodium was used to induce colitis in rats, which then underwent an enema with R. intestinalis as a treatment. The disease activity index, fecal changes and body weight of rats were recorded to evaluate colitis, while histological and immunohistochemical analyses were carried out to examine colon function, and 16S rRNA sequencing was performed to evaluate the gut microbiota change. Behavioral assays and immunohistochemical staining of brain were performed to assess the effect of R. intestinalis on the gut-brain axis.ResultsColitis-related symptoms in rats were significantly relieved after R. intestinalis enema, and the stool traits and colon length of rats were significantly recovered after treatment. The gut epithelial integrity and intestinal barrier were restored in treated rats, as evidenced by the higher expression of Zo-1 in colon tissues, accompanied by the restoration of gut microbiota. Meanwhile, depressive-like behaviors of rats were reduced after treatment, and laboratory experiments on neuronal cells also showed that IL-6, IL-7 and 5-HT were downregulated by R. intestinalis treatment in both serum and brain tissue, while Iba-1 expression was reduced in treated rats.ConclusionsThe administration of R. intestinalis contributes to restoration of the gut microbiota, promoting colon repair and the recovery of gastrointestinal function. These alterations are accompanied by the relief of depressive-like behaviors through a process modulated by the neuronal network and the regulation of inflammation by the gut-brain axis.

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Roseburia intestinalis supernatant ameliorates colitis induced in mice by regulating the immune response.

Publications

Roseburia intestinalis supernatant ameliorates colitis induced in mice by regulating the immune response.

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