Abstract

BackgroundUlcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an intensively studied human microbiome-associated disease, research on Chinese populations remains relatively limited, particularly on the mucosal microbiome. The present study aimed to analyze the changes in the mucosal microbiome associated with UC from the perspectives of medical ecology and complex network analysis.ResultsIn total, 56 mucosal microbiome samples were collected from 28 Chinese UC patients and their healthy family partners, followed by amplicon sequencing. Based on sequencing data, we analyzed species diversity, shared species, and inter-species interactions at the whole community, main phyla, and core/periphery species levels. We identified four opportunistic “pathogens” (i.e., Clostridium tertium, Odoribacter splanchnicus, Ruminococcus gnavus, and Flavonifractor plautii) with potential significance for the diagnosis and treatment of UC, which were inhibited in healthy individuals, but unrestricted in the UC patients. In addition, we also discovered in this study: (i) The positive-to-negative links (P/N) ratio, which measures the balance of species interactions or inhibition effects in microbiome networks, was significantly higher in UC patients, indicating loss of inhibition against potentially opportunistic “pathogens” associated with dysbiosis. (ii) Previous studies have reported conflicting evidence regarding species diversity and composition between UC patients and healthy controls. Here, significant differences were found at the major phylum and core/periphery scales, but not at the whole community level. Thus, we argue that the paradoxical results found in existing studies are due to the scale effect.ConclusionsOur results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC. The four opportunistic pathogens that were identified in the present study deserve further investigation in future studies.

Highlights

  • Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide

  • Our results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC

  • Correcting the gut microbiome or its functions in patients has become a target for IBD therapy, and can be achieved through various strategies, such as antibiotics, probiotics, and fecal microbial transplantation (FMT) [11, 32, 56, 63, 64]

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Summary

Introduction

Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. The pathogenesis of IBD remains unclear, may be related to the dysregulation of the internal mucosal environment due to changes in host genes, environmental factors, gut microbes, and immune responses [1, 28, 31, 35, 42, 45]. Common gut microbiome changes in IBD patients, for example, include a lower abundance of obligate anaerobic bacteria of short-chain fatty acids (SCFAs) and an increase in abundance of facultative anaerobes [15, 30, 42, 51, 59]. The species and microbial metabolites associated with oxidative stress responses are significantly increased in the gastrointestinal tract of IBD patients [16]. Correcting the gut microbiome or its functions in patients has become a target for IBD therapy, and can be achieved through various strategies, such as antibiotics, probiotics, and fecal microbial transplantation (FMT) [11, 32, 56, 63, 64]

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