# Early-Life Diarrhea Disrupts Antioxidant–Immune Homeostasis and Gut Microbiota in Suckling Calves

## TL;DR

Early-life diarrhea in calves disrupts gut health by causing oxidative stress, immune imbalance, and changes in gut microbes, which could lead to new strategies for improving calf health.

## Contribution

This study reveals how gut microbiota dysbiosis contributes to calf diarrhea and related physiological disruptions.

## Key findings

- Diarrhea in calves is linked to increased oxidative stress, immune imbalance, and disrupted intestinal barrier function.
- Diarrheic calves show reduced microbial diversity and enrichment of opportunistic pathogens.
- Microbial shifts favor carbohydrate metabolism over antioxidant and amino acid metabolism during diarrhea.

## Abstract

Calf diarrhea is one of the most common diseases affecting young calves and can lead to growth retardation, increased treatment costs, and even mortality. However, the biological mechanisms underlying diarrhea, particularly the role of gut microbiota, are not fully understood. In this study, we compared healthy calves and calves with diarrhea to investigate changes in fecal characteristics, antioxidant status, immune function, and gut microbial composition and function. We found that diarrhea was associated with increased fecal water content, oxidative stress, immune imbalance, and disruption of intestinal barrier function. At the microbial level, diarrheic calves showed reduced microbial diversity, enrichment of opportunistic pathogens, and alterations in metabolic functions. These findings suggest that gut microbiota imbalance plays a key role in the development of diarrhea and its related physiological disorders. Our study provides new insights into the microbial mechanisms of calf diarrhea and may contribute to the development of nutritional or microbiome-based strategies to improve calf health.

Calf diarrhea is a common early-life disorder that adversely affects growth, oxidative balance, immune function, and intestinal microbiota, thereby compromising health and production performance. This study systematically investigates the effects of naturally occurring diarrhea in 7-day-old suckling calves on oxidative stress, immune responses, intestinal barrier integrity, and gut microbiota structure and function. Fecal scores, serum antioxidant and immune indices, and intestinal permeability markers were measured, and fecal samples were subjected to metagenomic sequencing. Diarrhea-affected calves exhibited higher fecal scores, increased oxidative stress indicated by reduced total antioxidant capacity, elevated lipid peroxidation, and altered antioxidant enzyme activities. Humoral immunity was impaired, inflammatory responses were dysregulated, and intestinal barrier function was disrupted. Gut microbial diversity declined, showing a depletion in health-associated taxa and the enrichment of opportunistic pathogens. Correlation analyses revealed that pathogenic bacteria abundance positively associated with diarrhea severity, oxidative stress, inflammation, and barrier disruption, while beneficial genera correlated with antioxidant and immune function. Functional profiling indicated a microbial shift from amino acid metabolism and antioxidant homeostasis toward carbohydrate and energy metabolism under diarrheic conditions. These findings highlight the pivotal role of gut microbiota dysbiosis in diarrhea pathogenesis and provide a foundation for developing microbiome-targeted interventions to improve calf health.