Effect of feeding Chinese herb medicine ageratum-liquid on intestinal bacterial translocations induced by H9N2 AIV in mice

Haoran Lu,Qingmei Xie,Hongxin Li,Yihu Chen,Huanmin Zhang,Junfang Xiao,Che Wu,Luxuan Zhang,Wencheng Lin,Zhengyong Hu

doi:10.1186/s12985-019-1131-y

Abstract

BackgroundAs a low pathogenic influenza virus, avian influenza virus subtype H9N2 (H9N2 AIV) often induces high morbidity in association with secondary bacterial infections in chickens or mammals. To explore this phenomenon, the relationship between intestinal microflora changes and bacterial translocations was studied post H9N2 AIV challenge and post AIV infection plus Ageratum-liquid treatment.MethodsIllumina sequencing, histological examination and Neongreen-tagged bacteria were used in this study to research the microbiota composition, intestinal barrier, and bacterial translocation in six weeks of BALB/c mice.ResultsH9N2 AIV infection caused intestinal dysbacteriosis and mucosal barrier damages. Notably, the villus length was significantly reduced (p < 0.01) at 12 dpi and the crypt depth was significantly increased (p < 0.01) at 5 dpi and 12 dpi with infection, resulting in the mucosal regular villus-length/crypt-depth (V/C) was significantly reduced (p < 0.01) at 5 dpi and 12 dpi. Moreover, degeneration and dissolution of the mucosal epithelial cells, loose of the connective tissue and partial glandular atrophy were found in infection group, indicating that intestinal barrier function was weakened. Eventually, intestinal microbiota (Staphylococcus, E. coli, etc.) overrun the intestinal barrier and migrated to liver and lung tissues of the mice at 5 and 12 dpi. Furthermore, the bacteria transferred in mesentery tissue sites from intestine at 36 h through tracking the Neongreen-tagged bacteria. Then the Neongreen-tagged bacteria were isolated from liver at 48 h post intragastrical administration. Simultaneously, Ageratum-liquid could inhibit the intestinal microbiota disorder post H9N2 AIV challenge via the respiratory tract. In addition, this study also illustrated that Ageratum-liquid could effectively prevent intestinal bacterial translocation post H9N2 AIV infection in mice.ConclusionIn this study, we report the discovery that H9N2 AIV infection could damage the ileal mucosal barrier and induce the disturbance of the intestinal flora in BALB/c mice resulting in translocation of intestinal bacteria. In addition, this study indicated that Ageratum-liquid can effectively prevent bacterial translocation following H9N2 infection. These findings are of important theoretical and practical significance in prevention and control of H9N2 AIV infection.

Highlights

As a low pathogenic influenza virus, avian influenza virus subtype H9N2 (H9N2 Avian influenza virus subtype H9N2 (AIV)) often induces high morbidity in association with secondary bacterial infections in chickens or mammals
H9N2 AIV infection damaged the intestinal structure and induced intestinal bacterial translocations in mice To evaluate whether intestinal injury is a common feature for chickens [7] and mice infected with H9N2 AIV strain, we firstly detected live virus in cloacal swabs
H9N2 AIV strain was detected in all mice and the peak of virus shedding was observed at 5 dpi

Summary

Introduction

As a low pathogenic influenza virus, avian influenza virus subtype H9N2 (H9N2 AIV) often induces high morbidity in association with secondary bacterial infections in chickens or mammals. To explore this phenomenon, the relationship between intestinal microflora changes and bacterial translocations was studied post H9N2 AIV challenge and post AIV infection plus Ageratum-liquid treatment. The problem of bacterial secondary infection has plagued many scholars and clinical practitioners, and brought great difficulties to the prevention and control of the bird flu This is a puzzle that animal infection with influenza virus would appear serious bacterial secondary infection and how do these bacteria break through the body’s mucosal barrier into vital organs? This is a puzzle that animal infection with influenza virus would appear serious bacterial secondary infection and how do these bacteria break through the body’s mucosal barrier into vital organs? All of those questions deserve further research

Methods

Results

Discussion

Conclusion