Capsaicin Modulates Hepatic and Intestinal Inflammation and Oxidative Stress by Regulating the Colon Microbiota

Area of Science:

• Gastroenterology
• Immunology
• Microbiology

Background:

• Lipopolysaccharide (LPS) is a potent inducer of inflammation and oxidative stress in the liver and intestines.
• Capsaicin (CAP), the active component of chili peppers, possesses known anti-inflammatory and antioxidant properties.
• The impact of CAP on LPS-induced gut dysbiosis and its specific effects on colonic microflora remain to be fully elucidated.

Purpose of the Study:

• To investigate the protective effects of capsaicin against lipopolysaccharide-induced hepatic and intestinal inflammation and oxidative stress in a mouse model.
• To analyze the modulation of colonic microflora by capsaicin in the context of LPS-induced inflammation.
• To explore the relationship between capsaicin's anti-inflammatory and antioxidant actions and its effects on gut microbiota composition.

Main Methods:

• Thirty male Kunming mice were divided into three groups: control, LPS-induced, and LPS + CAP.
• Mice received daily treatments of normal saline or capsaicin for 28 days, followed by LPS injection in the respective groups.
• Histological analysis, cytokine level measurements (IL-10, IL-6, IL-1β, TNF-α), oxidative stress markers (CAT, GSH-Px, SOD, MDA), and 16S rRNA gene sequencing for gut microbiota analysis were performed.

Main Results:

• CAP administration significantly ameliorated LPS-induced hepatic damage and improved duodenal villus morphology.
• CAP treatment increased anti-inflammatory cytokine IL-10 while decreasing pro-inflammatory cytokines IL-6, IL-1β, and TNF-α in the liver and colon.
• CAP enhanced antioxidant enzyme expression (CAT, GSH-Px, SOD) and reduced lipid peroxidation (MDA) in the liver. It also altered the relative abundance of specific gut bacteria, including an increase in *Mucispirillum* and *Helicobacter*.
• CAP decreased overall short-chain fatty acids, with the exception of propionic acid.

Conclusions:

• Capsaicin demonstrates significant anti-inflammatory and antioxidant effects in an LPS-induced mouse model, protecting hepatic and intestinal tissues.
• CAP modulates the colonic microflora, potentially contributing to its therapeutic effects, with notable increases in *Mucispirillum* and *Helicobacter* species.
• Further research is warranted to confirm the causal role of CAP-induced microbiota alterations, particularly *Mucispirillum* and *Helicobacter* spp., in mediating its anti-inflammatory and antioxidant benefits.