# Oral pretreatment with Escherichia coli Nissle 1917 enhances the host's defense against influenza A virus infection

## TL;DR

Oral administration of Escherichia coli Nissle 1917 helps protect mice against influenza virus infection by altering gut bacteria and boosting pipecolic acid levels.

## Contribution

This study identifies E. coli Nissle 1917 and pipecolic acid as potential agents for preventing influenza by modulating gut microbiota.

## Key findings

- Oral E. coli Nissle 1917 reduced influenza symptoms and weight loss in infected mice.
- The protective effects are linked to increased Bacteroides and Akkermansia bacteria and elevated pipecolic acid levels.
- Modulation of gut microbiota and metabolism contributes to defense against influenza virus infection.

## Abstract

Influenza A viruses (IAVs) pose a significant threat to global health, causing annual epidemics and occasional pandemics with substantial morbidity and mortality. Despite the availability of vaccines and antiviral therapies, the development of novel preventive and therapeutic strategies remains a critical research focus. In this study, we evaluated the protective effects of orally administering Escherichia coli Nissle 1917 in IAV‐infected mice and elucidated its mechanisms of action by analyzing cecal microbiota and plasm metabolome profiles. Oral administration of E. coli Nissle 1917 alleviated respiratory symptoms, reduced weight loss, and mitigated pathological injury in mice infected with H9N2 or H1N1 IAV. These protective effects were mediated through the modulation of gut microbiota diversity, which increased the abundance of Bacteroides and Akkermansia, correlating with elevated pipecolic acid levels and ultimately aiding in defense against IAV infection in mice. Notably, we identified that the circulating metabolic molecule pipecolic acid plays a significant role in fighting IAV infection. Our findings suggest the potential usefulness of E. coli Nissle 1917 or pipecolic acid in influenza prevention.

In our pursuit of novel or universal antiviral strategies against influenza, we found vigorous anti‐influenza activity of orally administered Escherichia coli Nissle 1917 in a mouse model. The protective effects are associated with alterations in the host's gut microbiota and metabolism, as well as the modulation of cytokine expression induced by E. coli Nissle 1917 administration. Elevated levels of specific bacteria, including Bacteroides and Akkermansia, may enhance the secretion of pipecolic acid, thereby contributing to the defense against influenza virus infection. Importantly, our study underscores the potential of E. coli Nissle 1917 and pipecolic acid as promising agents for influenza prevention.