Intestinal microbiota has important effect on severity of hand foot and mouth disease in children

Hui Wang,Yi Xu,Rongrong Zou,Huanwei Huang ,Yujin Jiang,Chenguang Shen,Jianmin Li,Jinli Wei,Fengxia Yang,Fansen Zeng,Xianfeng Wang,Xinfa Wang,Jing Yuan,Jingkai Ji,Yang Yang,Mei Yang ,Huimin Xia,Chunxiao Fang,Yingxia Liu,Sitang Gong,Huanming Yang,Jinmin Ma

doi:10.1186/s12879-021-06748-7

Abstract

BackgroundThe incidence of hand foot and mouth disease (HFMD) has increased in recent years, making it a very common childhood illness worldwide. The relationship between different enterovirus genotypes and disease severity is not clearly understood. Given that enteroviruses are transmitted through the gastrointestinal tract, we hypothesized that variation in intestinal microorganisms of the host might play a role in the prognosis of HFMD.MethodsWe carried out a meta-transcriptomic-wide association study of fecal samples obtained from a cohort of children (254 patients, 227 tested positive for enterovirus, including 16 patients co-infectied with 2 kinds of enterovirus) with mild and severe HFMD and healthy controls.ResultsWe found there was no significant difference in the amount of each virus type between the mild and severe cases. Genes of enterovirus 71 (EV71) and coxsackievirus A (CV-A) from the severe and mild cases did not show significant clustering. Clostridium sp. L2-50 and Bacteroides stercoris ATCC 43183 were enriched in the guts of children with severe HFMD and KEGG enrichment was found between mild and severe cases.ConclusionsIntestinal microorganisms appear to interact with enterovirus to determine the progression of HFMD. Genes of Bacteroides and Clostridium may be used as predictive markers for a more efficient prognosis and intervention. The enrichment of intestinal bacteria genes with functions may facilitate the development of severe symptoms for HFMD patients.

Highlights

The incidence of hand foot and mouth disease (HFMD) has increased in recent years, making it a very common childhood illness worldwide
enterovirus 71 (EV71) was detected at a higher rate in the severe cases, whereas coxsackievirus A4 (CV-A4) was detected at a higher rate among the mild cases (Fisher’s exact test, p < 0.05)
EV71 plus CAV16 infection when compared to quantitative real-time polymerase chain reaction (RT-PCR); overall, 10 kinds of co-infection were identified in this study, and 4 virus types showed co-infection with EV71

Summary

Introduction

The incidence of hand foot and mouth disease (HFMD) has increased in recent years, making it a very common childhood illness worldwide. Enterovirus 71 and coxsackievirus A16 (CV-A16) were the most common HFMD-causing pathogens reported; since 2010, coxsackievirus A6 (CVA6) emerged as the most common serotype in Shenzhen, China [1, 2], and was found in an outbreak of CV-A6-associated HFMD in China since 2013 [3]. It even became a lethal strain in northeast China [4]. Coxsackievirus A4 (CV-A4) and A10 (CVA10) have become increasingly common in recent years, which has coincided with the emergence of more severe cases of HFMD. There is no useful clinical indicator for predicting the severity of disease upon diagnosis

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Discussion

Conclusion