# Distinct actions of the humid heat environment on host gut microbiota, intestinal mucosal immunity, neuroendocrinology in influenza A virus-infected mouse

## TL;DR

Exposure to a humid heat environment worsens influenza symptoms in mice by disrupting gut health and reducing neurotransmitters, leading to anxiety and depression-like behaviors.

## Contribution

This study reveals how environmental stress, like humid heat, exacerbates influenza through gut microbiota disruption and neuroendocrine changes.

## Key findings

- Humid heat exposure worsened intestinal inflammation and gut microbiota dysbiosis in influenza-infected mice.
- Neurotransmitter levels were reduced, correlating with anxiety- and depression-like behaviors in infected mice.
- Environmental stress disrupted intestinal homeostasis and worsened influenza severity.

## Abstract

Climate factors exert a profound influence on human emotional well-being and physical health. Exposure to a humid heat environment is known to precipitate anxiety-like behaviors and exacerbate the clinical manifestations of influenza; concurrently, mounting evidence has demonstrated a bidirectional regulation between the gut microbiota and human health, suggesting a potential link between environmental stress and microbial homeostasis.

In this study, C57BL/6J male mice were subjected to a humid heat environment for 3 weeks prior to infection with the influenza A virus. Microbiota composition, metabolites, and intestinal mucosal immunity were comprehensively measured. Furthermore, behavioral phenotypes and neurotransmitter levels were assessed to explore their potential correlations with gut dysbiosis.

Exposure to a humid heat environment aggravated pulmonary and intestinal tissue damage while reshaping the gut microbiota composition and metabolome. This environmental stress precipitated severe pathological injury and robust inflammatory in the intestinal mucosa, characterized by a multifold upregulation of Th1/Th2-related cytokines and the suppressed expression of Ocln, ZO-1, pIgR, and SIgA. Further experiments revealed that the humid heat environment exacerbated neurological deficits in influenza A virus-infected mice, accompanied by a significant reduction in neurotransmitter levels. Conclusions: These data demonstrate that exposure to a humid heat environment exacerbates influenza infection severity through the dysregulation of the intestinal homeostasis and the neuroendocrine system, revealing the potential mechanisms underlying the digestive and nervous system symptoms observed in influenza patients.

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•Exposure to a humid heat environment exacerbated gut microecological dysbiosis in IAV-infected mice.•Humid-heat exposure resulted in more severe intestinal inflammatory responses.•Reduced key neurotransmitters were observed in IAV-infected mice under humid heat conditions.•These changes were associated with aggravated anxiety- and depression-like behaviors in the IAV mouse model.

Exposure to a humid heat environment exacerbated gut microecological dysbiosis in IAV-infected mice.

Humid-heat exposure resulted in more severe intestinal inflammatory responses.

Reduced key neurotransmitters were observed in IAV-infected mice under humid heat conditions.

These changes were associated with aggravated anxiety- and depression-like behaviors in the IAV mouse model.