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Investigating the Alleviating Effects of Bacillus cereus Administration on Colitis through Gut Microbiota Modulation
Published on: July 27, 2022
Real-world of Limosilactobacillus reuteri in mitigation of acute experimental colitis
Ningning Yue1, Hailan Zhao1,2, Peng Hu3
1Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, 518020, China.
Abstract:
Probiotics have been proposed as a potential strategy for managing ulcerative colitis (UC). However, the underlying mechanisms mediating microbiota-host crosstalk remain largely elusive. Here, we report that Limosilactobacillus reuteri (L. reuteri), as a probiotic, secretes cytoplasmic membrane vesicles (CMVs) that communicate with host cells, alter host physiology, and alleviate dextran sulfate sodium (DSS)-induced colitis. First, L. reuteri-CMVs selectively promoted the proliferation of the beneficial bacterium Akkermansia muciniphila (AKK) by upregulating the expression of glycosidases (beta-N-acetylhexosaminidase and alpha-N-acetylglucosaminidase) involved in glycan degradation and metabolic pathways and restored the disrupted gut microbiota balance. Second, L. reuteri-CMVs were taken up by intestinal epithelial cells (IECs), elevated the expression of ZO-1, E-cadherin (Cdh1), and Occludin (Ocln), decreased intestinal permeability, and exerted protective effects on epithelial tight junction functionality. RNA sequencing analysis demonstrated that L. reuteri-CMVs repaired intestinal barrier by activating the HIF-1 signaling pathway and upregulating HMOX1 expression. Third, L. reuteri-CMVs increased the population of double positive (DP) CD4+CD8+ T cells in the intestinal epithelial layer, suppressing gut inflammation and maintaining gut mucosal homeostasis. Finally, L. reuteri-CMVs exhibited satisfactory stability and safety in the gastrointestinal tract and specifically targeted the desired sites in colitis mice. Collectively, these findings shed light on how L. reuteri interact with the host in colitis, and provide new insights into potential strategies for alleviating colitis.
Insights
Limosilactobacillus reuteri cytoplasmic membrane vesicles (CMVs) alleviate ulcerative colitis (UC) by enhancing beneficial bacteria, strengthening the gut barrier, and modulating immune cells. These findings offer new therapeutic strategies for managing gut inflammation.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Ulcerative colitis (UC) management remains challenging, with limited understanding of probiotic mechanisms.
- Probiotics like Limosilactobacillus reuteri (L. reuteri) show potential, but their interaction with host cells requires elucidation.
Purpose of the Study:
- To investigate the mechanisms by which L. reuteri-derived cytoplasmic membrane vesicles (CMVs) alleviate dextran sulfate sodium (DSS)-induced colitis.
- To explore the effects of L. reuteri-CMVs on gut microbiota, intestinal epithelial cells, and immune responses.
Main Methods:
- Isolation and characterization of L. reuteri-CMVs.
- In vitro and in vivo studies using DSS-induced colitis models.
- Analysis of gut microbiota composition, intestinal permeability, epithelial barrier function, and immune cell populations.
- RNA sequencing to identify molecular pathways involved.
Main Results:
- L. reuteri-CMVs selectively promoted Akkermansia muciniphila (AKK) proliferation, restoring gut microbiota balance.
- CMVs were internalized by intestinal epithelial cells (IECs), enhancing tight junction proteins (ZO-1, Cdh1, Ocln) and reducing intestinal permeability.
- RNA sequencing revealed that CMVs activate the HIF-1 signaling pathway and upregulate HMOX1, repairing the intestinal barrier.
- CMVs increased CD4+CD8+ T cells in the intestinal epithelium, suppressing inflammation and maintaining mucosal homeostasis.
- L. reuteri-CMVs demonstrated stability, safety, and targeted delivery in colitis models.
Conclusions:
- L. reuteri-CMVs represent a novel therapeutic agent for ulcerative colitis.
- The study elucidates key mechanisms of microbiota-host crosstalk mediated by bacterial vesicles.
- These findings provide a foundation for developing vesicle-based probiotics for inflammatory bowel disease.
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