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Published on: May 2, 2018
Probiotic Bacillus pumilus LV149 enhances gut repair, modulates microbiota, and alters transcriptome in DSS-induced
Xinyu Sun1, Long Yun2, Keming Xie3
1School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
Purpose:
Gut microbiota dysbiosis significantly impacts ulcerative colitis (UC) progression and exacerbation. Probiotics show promise in UC management. This study evaluated the effects of different doses of Bacillus pumilus LV149, an aquatic-derived probiotic, on gut injury repair in male C57BL/6 mice with dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and investigated the underlying mechanisms.
Methods:
UC was induced by allowing mice free access to a 3% DSS solution for 7 days, with concurrent daily oral gavage of either a low (LV149-L, 1 × 108 CFU/day/mouse) or high (LV149-H, 1 × 109 CFU/day/mouse) dose of LV149. The effects were assessed through physiological parameters, intestinal barrier integrity, inflammation, gut microbiota composition, and transcriptomic changes.
Results:
LV149 significantly improved pathological symptoms, including weight loss and disease activity index (DAI), and reduced colon shortening in a dose-dependent manner and inflammatory damage. The intervention also restored gut barrier function by upregulating mucins, goblet cell counts, and tight junction proteins (ZO-1, occludin, and claudin-1) in colonic tissue, along with reducing serum lipopolysaccharide (LPS) levels. Notably, only the LV149-H significantly decreased the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, while both doses increased the expression of the anti-inflammatory cytokine IL-10 in a dose-dependent in colonic tissue. LV149 further modulated the gut microbiota, increasing beneficial bacteria and reducing pathogenic populations. Transcriptomic analysis indicated that LV149-L may exert gut repair effects via the IL-17 signaling pathway, whereas LV149-H appears to act through the JAK-STAT signaling pathway.
Conclusion:
This study demonstrated that LV149, particularly at a higher dose, effectively mitigated DSS-induced colonic injury by modulating gut microbiota, enhancing gut barrier integrity, and reducing inflammation. The dose-dependent effects underscored LV149-H's potential as a therapeutic agent for UC due to its stronger anti-inflammatory properties and gut-protective effects.
Insights
Bacillus pumilus LV149, a probiotic, effectively repaired gut injury in ulcerative colitis (UC) mouse models. A higher dose (LV149-H) showed stronger anti-inflammatory and gut-protective effects, suggesting its therapeutic potential for UC.
Area of Science:
- Microbiology and Immunology
- Gastroenterology
- Probiotic Research
Background:
- Gut microbiota dysbiosis is a key factor in ulcerative colitis (UC) progression.
- Probiotics are being investigated as a potential therapeutic strategy for managing UC.
- Understanding the specific mechanisms of probiotic action in UC is crucial for effective treatment.
Purpose of the Study:
- To evaluate the efficacy of different doses of Bacillus pumilus LV149 in repairing gut injury in a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model.
- To investigate the underlying mechanisms, including effects on gut barrier integrity, inflammation, and gut microbiota composition.
- To determine if the effects are dose-dependent.
Main Methods:
- Ulcerative colitis was induced in male C57BL/6 mice using 3% DSS solution.
- Mice received daily oral gavage of either a low (1 × 10^8 CFU/day) or high (1 × 10^9 CFU/day) dose of Bacillus pumilus LV149.
- Assessment included physiological parameters, disease activity index (DAI), colon length, intestinal barrier integrity markers (mucins, tight junctions), inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IL-10), serum lipopolysaccharide (LPS), gut microbiota composition, and transcriptomic analysis.
Main Results:
- Bacillus pumilus LV149 significantly improved UC symptoms, including weight loss and DAI, and reduced colon shortening in a dose-dependent manner.
- LV149 restored gut barrier function by upregulating mucins and tight junction proteins and reducing serum LPS.
- The high dose (LV149-H) significantly reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and increased anti-inflammatory IL-10, while both doses increased IL-10 expression. Transcriptomic analysis suggested different pathways for low (IL-17) and high (JAK-STAT) dose effects.
Conclusions:
- Bacillus pumilus LV149, particularly at a higher dose, effectively mitigates DSS-induced colonic injury in mice.
- The probiotic enhances gut barrier integrity, reduces inflammation, and modulates gut microbiota composition.
- The dose-dependent anti-inflammatory and gut-protective effects of LV149-H highlight its potential as a therapeutic agent for ulcerative colitis.
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