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The Probiotic VSL#3 Modulates Colonic Macrophages, Inflammation, and Microflora in Acute Trinitrobenzene Sulfonic
Raymond A Isidro1, Abdon Lopez2, Myrella L Cruz1
1Department of Basic Sciences, Medical School and Ponce Research Institute, Ponce Health Sciences University, Ponce, Puerto Rico (RAI, MLC, AAI, CBA).
Abstract:
The probiotic mixture VSL#3 attenuates colitis in patients with Inflammatory Bowel Disease (IBD) and in animal models of this condition, but the mechanisms involved are incompletely understood. VSL#3 alters macrophage morphology and secretory profile in vitro in a polarization-dependent manner. We examined the effect of VSL#3 on macrophages in acute trinitrobenzene sulfonic acid-induced colitis. Rats were randomized to normal, colitis, or colitis+VSL#3 groups. After sacrifice, the colons were evaluated for macroscopic and microscopic damage. Serum cytokine levels were measured, and microbiome analysis undertaken. Total and M1 colonic macrophages, and total and proliferating hepatic macrophages were assessed by double immunofluorescence staining. Colitis+VSL#3 rats had lower macroscopic damage, with less microscopic damage in the proximal colon, compared with colitis alone. Colitis significantly increased colonic macrophage infiltration, which was significantly reduced by VSL#3 treatment. VSL#3 did not decrease the colitis-induced surge of colonic M1 macrophages or hepatic macrophages. VSL#3 reduced colitis-induced serum cytokine levels, and induced restoration of colonic transcript levels for pro-inflammatory, anti-inflammatory, and barrier proteins to, or past, normal levels. Fecal bacteria distribution changed between groups. In summary, the probiotic VSL#3 reduces colitis severity, colonic macrophage infiltration, and serum cytokine levels, but does not dampen the pro-inflammatory phenotype of M1 macrophages.
Insights
The probiotic VSL#3 reduces Inflammatory Bowel Disease (IBD) severity and macrophage infiltration in the colon. While it lowers serum cytokine levels, VSL#3 does not alter the pro-inflammatory M1 macrophage phenotype in colitis models.
Area of Science:
- Gastroenterology
- Immunology
- Microbiology
Background:
- Inflammatory Bowel Disease (IBD) is a chronic condition characterized by gut inflammation.
- The probiotic VSL#3 has shown therapeutic potential in IBD patients and animal models.
- Mechanisms underlying VSL#3's effects on IBD, particularly involving macrophages, require further elucidation.
Purpose of the Study:
- To investigate the impact of VSL#3 on macrophage behavior during acute trinitrobenzene sulfonic acid-induced colitis in rats.
- To assess the effects of VSL#3 on colonic damage, immune cell infiltration, and systemic inflammation.
Main Methods:
- Rats were induced with colitis and treated with either VSL#3 or a placebo.
- Macroscopic and microscopic colonic damage were evaluated.
- Colonic and hepatic macrophage populations, serum cytokine levels, and colonic gene expression were analyzed.
Main Results:
- VSL#3 treatment significantly reduced macroscopic and microscopic colonic damage.
- VSL#3 decreased overall colonic macrophage infiltration but did not reduce M1 pro-inflammatory macrophages.
- Serum cytokine levels were reduced, and colonic gene expression for inflammatory and barrier proteins was restored by VSL#3.
Conclusions:
- VSL#3 ameliorates colitis severity and reduces colonic macrophage infiltration.
- The probiotic's therapeutic effect is not mediated by dampening the M1 macrophage pro-inflammatory phenotype.
- VSL#3 modulates systemic inflammation and restores intestinal barrier function during colitis.
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