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. 2021 Jul 6;11(1):13945.
doi: 10.1038/s41598-021-93345-y.

Gut microbiota signature of pathogen-dependent dysbiosis in viral gastroenteritis

Taketoshi Mizutani  1 , Samuel Yaw Aboagye  2 , Aya Ishizaka  3 , Theophillus Afum  2 , Gloria Ivy Mensah  2 , Adwoa Asante-Poku  2 , Diana Asema Asandem  2 , Prince Kofi Parbie  2   4   5 , Christopher Zaab-Yen Abana  2 , Dennis Kushitor  2 , Evelyn Yayra Bonney  2 , Motoi Adachi  6 , Hiroki Hori  6 , Koichi Ishikawa  5 , Tetsuro Matano  3   4   5 , Kiyosu Taniguchi  7 , David Opare  8 , Doris Arhin  8 , Franklin Asiedu-Bekoe  8 , William Kwabena Ampofo  2 , Dorothy Yeboah-Manu  2 , Kwadwo Ansah Koram  2 , Abraham Kwabena Anang  2 , Hiroshi Kiyono  3   9   10
Affiliations

Gut microbiota signature of pathogen-dependent dysbiosis in viral gastroenteritis

Taketoshi Mizutani et al. Sci Rep. .

Abstract

Acute gastroenteritis associated with diarrhea is considered a serious disease in Africa and South Asia. In this study, we examined the trends in the causative pathogens of diarrhea and the corresponding gut microbiota in Ghana using microbiome analysis performed on diarrheic stools via 16S rRNA sequencing. In total, 80 patients with diarrhea and 34 healthy adults as controls, from 2017 to 2018, were enrolled in the study. Among the patients with diarrhea, 39 were norovirus-positive and 18 were rotavirus-positive. The analysis of species richness (Chao1) was lower in patients with diarrhea than that in controls. Beta-diversity analysis revealed significant differences between the two groups. Several diarrhea-related pathogens (e.g., Escherichia-Shigella, Klebsiella and Campylobacter) were detected in patients with diarrhea. Furthermore, co-infection with these pathogens and enteroviruses (e.g., norovirus and rotavirus) was observed in several cases. Levels of both Erysipelotrichaceae and Staphylococcaceae family markedly differed between norovirus-positive and -negative diarrheic stools, and the 10 predicted metabolic pathways, including the carbohydrate metabolism pathway, showed significant differences between rotavirus-positive patients with diarrhea and controls. This comparative study of diarrheal pathogens in Ghana revealed specific trends in the gut microbiota signature associated with diarrhea and that pathogen-dependent dysbiosis occurred in viral gastroenteritis.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Beta diversities in fecal microbiome in adult patients with diarrhea and healthy adult cohorts. (A) Weighted Unifrac distances of fecal microbiome in individuals with diarrhea and healthy adult cohorts. Weighted unifrac distances to healthy controls indicates that individuals with diarrhea possess significantly distant fecal microbiome composition (PERMANOVA, q = 0.002). (B) Principal coordinate analysis (PCoA) plots based on Bray–Curtis diversity metric. (C) Comparing weighted Unifrac distances of fecal microbiome among individuals with diarrhea including viral none-detectable diarrhea (None), norovirus detected diarrhea (Norovirus), and rotavirus detected diarrhea (Rotavirus), to healthy controls. Fecal microbiome composition of individuals with Norovirus infection are significantly distant from healthy controls (PERMANOVA, q = 0.01). **, *** indicate PERMANOVA significant differences with q =  < 0.01, and < 0.005 respectively.
Figure 2
Figure 2
Fecal bacteria abundance at the phylum level by STAMP analysis. Comparison of gut microbiota between the healthy adult controls and adult patients with diarrhea by STAMP analysis at the phylum level (A) and genus level (B). HC healthy adult control, Diarrhea adult patient with diarrhea.
Figure 3
Figure 3
Taxonomic profiles (genus) of fecal bacteria in patients with diarrhea and healthy controls. Top 10 relative abundance of fecal taxa at the phylum level in healthy adult controls (A) and patients with diarrhea; adults (B), adolescents (C), and children (D).
Figure 4
Figure 4
Comparison of fecal microbiota between adult patients with diarrhea and healthy controls. Identification of difference of bacterial markers in gut microbiota between adult patients with diarrhea and healthy controls using LEfSe analysis (A) and LDA score > 3.0 (B). The cladogram was calculated and depicted by LEfSe, a major metagenomic analysis method. The effect size of each taxon or OUT with different quantities was evaluated by Wilcoxon sum-rank test followed by liner discriminant analysis.
Figure 5
Figure 5
Comparing fecal bacteria abundance between enterovirus positive and negative diarrhea patients. Comparison of gut microbiota between enterovirus positive or negative diarrhea patients by STAMP analysis. (A) The difference of gut microbiota between norovirus detected and non-viral detected diarrhea patients at the family level (A) and genus level (B). The difference of gut microbiota between rotavirus positive and non-viral detected diarrhea patients at the genus level (C).
Figure 6
Figure 6
Distribution of Kyoto Encyclopedia of Genes and Genomes (KEGG) functional categories. Comparison between healthy controls and rotavirus-positive patients with diarrhea on levels 2 (A) and 3 (B) of KEGG. Functional contributions of the gut microbiota were analyzed using PICRUSt software.
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