Fecal microbiota transplantation attenuates Escherichia coli infected outgrowth by modulating the intestinal microbiome

Abstract

Background: Given the crucial role of gut microbiota in animal and human health, studies on modulating the intestinal microbiome for therapeutic purposes have grasped a significant attention, of which the role of fecal microbiota transplantation (FMT) has been emphasized.

Methods: In the current study, we evaluated the effect of FMT on gut functions in Escherichia coli (E. coli) infection by using mice model. Moreover, we also investigated the subsequently dependent variables of infection, i.e., body weight, mortality, intestinal histopathology, and the expression changes in tight junction proteins (TJPs).

Results: The FMT effectively decreased weight loss and mortality to a certain extent with the restoration of intestinal villi that resulted in high histological scores for jejunum tissue damage (p < 0.05). The effect of FMT on alleviating the reduction of intestinal TJPs was also proved by immunohistochemistry analysis and mRNA expression levels. Moreover, the abundance of health-threatening bacteria, belonging to phylum Proteobacteria, family Enterobacteriaceae and Tannerellaceae, genus Escherichia-Shigella, Sphingomonas, Collinsella, etc., were significantly increased, whereas beneficial bacteria, belonging to phylum Firmicutes, family Lactobacillaceae, genus Lactobacillus were decreased in the gut of infected mice. Furthermore, we sought to investigate the association of clinical symptoms with FMT treatment with modulation in gut microbiota. According to beta diversity, the microbial community of gut microbiota results reflected the similarities between non-infected and FMT groups. The improvement of the intestinal microbiota in FMT group was characterized by the significant high level of beneficial microorganisms with the synergistic decrease of Escherichia-Shigella, Acinetobacter, and other taxa.

Conclusion: The findings suggest a beneficial host-microbiome correlation following fecal microbiota transplanatation for controlling gut infections and pathogens-associated diseases.

Keywords: Escherichia coli; Fecal microbiota transplantation; Intestinal injury; Intestinal microbiome.

Fig. 1

The flowchart of experiment

Fig. 2

Evaluation of body weight loss, survival rate and gut damage after E. coli infection. A, body weight. B, survival rate. C, histological score. D, the mRNA expression levels of TJPs in the jejunum. * p < 0.05, ** p < 0.01

Fig. 3

Jejunum histopathological and immunohistochemical changes in different groups. Bar = 50 µm

Fig. 4

Structural changes of jejunum microbiota. A–C represent the number of OTUs in groups, i.e., Con, Eco, and FMT. D represent the number of common and core OTUs among the groups. E, F represent Histograms and Cladogram of enriched taxa based on LEfSe determinations, respectively. Microbial classification with an LDA score ≤ 5 was selected as biomarker microorganisms (p phylum, c class, o order, f family, g genus). G represented the genus-level phylogenetic tree

Fig. 5

Analysis of sequencing quality, gut microbial alpha, and beta diversities. A, Alpha diversity; B, Rarefaction curve; C, Shannon curve; D, Species accumulation curve; E, NMDS, The closer samples on the coordinate map, shows higher similarity between samples; F, UPGMA, The closer samples are more similar in composition; G, Clustering heatmap, The color gradient from blue to red indicated the distance between samples from near to far. * p < 0.05, ** p < 0.01

Fig. 6

Relative abundances of jejunum microbiota at multiple levels. A–C The phylum, family, and genus level among groups. D–F The phylum, family, and genus levels between individual samples

Fig. 7

The correlation of microbial species and the significant changes in microbial composition between groups. A, Correlation network diagram based on spearman analysis; B, Significantly changes in microbial composition between groups. * p < 0.05, ** p < 0.01