Ochratoxin A induces liver inflammation: involvement of intestinal microbiota

Wence Wang,Hongfu Zhang,Shuangshuang Zhai,Yaoyao Xia,Lin Yang,Yongwen Zhu,Minhong Zhang,Ting Zhou,Hao Wang,Wenkai Ren,Dong Ruan,Hui Ye

doi:10.1186/s40168-019-0761-z

Abstract

BackgroundOchratoxin A (OTA) is a widespread mycotoxin and induces liver inflammation to human and various species of animals. The intestinal microbiota has critical importance in liver inflammation; however, it remains to know whether intestinal microbiota mediates the liver inflammation induced by OTA. Here, we treated ducklings with oral gavage of OTA (235 μg/kg body weight) for 2 weeks. Then, the microbiota in the cecum and liver were analyzed with 16S rRNA sequencing, and the inflammation in the liver was analyzed. To explore the role of intestinal microbiota in OTA-induced liver inflammation, intestinal microbiota was cleared with antibiotics and fecal microbiota transplantation was conducted.ResultsHere, we find that OTA treatment in ducks altered the intestinal microbiota composition and structure [e.g., increasing the relative abundance of lipopolysaccharides (LPS)-producing Bacteroides], and induced the accumulation of LPS and inflammation in the liver. Intriguingly, in antibiotic-treated ducks, OTA failed to induce these alterations in the liver. Notably, with the fecal microbiota transplantation (FMT) program, in which ducks were colonized with intestinal microbiota from control or OTA-treated ducks, we elucidated the involvement of intestinal microbiota, especially Bacteroides, in liver inflammation induced by OTA.ConclusionsThese results highlight the role of gut microbiota in OTA-induced liver inflammation and open a new window for novel preventative or therapeutic intervention for mycotoxicosis.

Highlights

Ochratoxin A (OTA) is a widespread mycotoxin and induces liver inflammation to human and various species of animals
Oral OTA gavage alters cecum microbiota composition and promotes cecum LPS biosynthesis in ducks To explore the effects of oral OTA gavage on 21-day ducks, OTA residue, feed intake, final weight, weight gain, and feed/gain ratio were monitored during the experiment
To explore the effect of OTA on intestinal microbiota, cecum microbiota of ducks was analyzed by sequencing the cecum bacterial 16S rRNA V3 + V4 region and metagenomics

Summary

Introduction

Ochratoxin A (OTA) is a widespread mycotoxin and induces liver inflammation to human and various species of animals. Mycotoxins are secondary metabolites produced by fungal genera (e.g., Aspergillus, Penicillium, and Fusarium) and are the most common natural food contaminants in human and animal diets, such as cereals and animal forages [1,2,3]. Ochratoxin A (OTA), the most prevalent and relevant fungal toxin produced by Aspergillus species and Penicillium species [4], is found to be one of the most common contaminants in cereals, coffee, wine, dried fruits and nuts, meat products [5], herbal medicines [6,7,8], food coloring agents [9], and even in bottled water [10]. Intestinal microbiota highly shapes the intestinal barrier function and the physiological function of

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