# Microcin C7 Prevents Cyclophosphamide-Induced Immunosuppression and Intestinal Injury by Modulating T-Cell Differentiation and Gut Microbiota Composition in Mice

## TL;DR

Microcin C7 helps prevent intestinal and immune damage caused by cyclophosphamide in mice by improving gut health and T-cell balance.

## Contribution

This study shows that McC7 can modulate gut microbiota and T-cell differentiation to counteract cyclophosphamide-induced immunosuppression.

## Key findings

- McC7 reduced body weight loss and organ damage caused by cyclophosphamide.
- McC7 improved the gut microbiota by increasing beneficial bacteria and reducing harmful ones.
- McC7 restored the CD4+/CD8+ T-cell ratio and supported intestinal barrier integrity.

## Abstract

Microcin C7 (McC7) is a ribosomally synthesized antimicrobial peptide that has emerged as a promising candidate due to its dual antibacterial and immunomodulatory activities. This study evaluated the preventive effect of McC7 against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. An immunosuppression model was established by intraperitoneal CTX injection in mice, which were randomly allocated into five groups (n = 15): a negative control, a CTX model group, and three McC7 treatment groups receiving dietary McC7 at 100, 200, or 400 mg/kg both before and during CTX exposure. Body weight and feed intake were monitored throughout the study. Organ indices, serum biochemical parameters, immune and antioxidant markers, and intestinal morphology were assessed. Splenic T-cell subsets were analyzed by flow cytometry, and gut microbiota composition was evaluated by 16S rRNA sequencing. McC7 supplementation significantly attenuated the CTX-induced reduction in body weight, feed intake, and organ indices, ameliorated markers of hepatic and renal injury, and restored the splenic CD4+/CD8+ T-cell ratio. McC7 enhanced intestinal mucosal barrier integrity, increased the abundance of beneficial bacteria such as Candidatus Arthromitus and ASF356, and reduced the abundance of the potentially pathogenic genus Bilophila. In conclusion, our results demonstrate that McC7 alleviates CTX-induced immunosuppression by regulating T-cell differentiation, maintaining cytokine homeostasis, and modulating gut microbial composition to support intestinal health.