Intest Res.  2023 Jan;21(1):148-160. 10.5217/ir.2021.00168.

Compositional changes in fecal microbiota associated with clinical phenotypes and prognosis in Korean patients with inflammatory bowel disease

• Shin SY
• Kim Y
• Kim WS
• Moon JM
• Lee KM
• Jung SA
• Park H
• Huh EY
• Kim BC
• Lee SC
• Choi CH
• on behalf of the IBD Research Group of the Korean Association for the Study of Intestinal Diseases

• KMID: 2539013
• DOI: http://doi.org/10.5217/ir.2021.00168

Abstract

Background/Aims
The fecal microbiota of Korean patients with inflammatory bowel disease (IBD) was investigated with respect to disease phenotypes and taxonomic biomarkers for diagnosis and prognosis of IBD.
Methods
Fecal samples from 70 ulcerative colitis (UC) patients, 39 Crohn’s disease (CD) patients, and 100 healthy control individuals (HC) were collected. The fecal samples were amplified via polymerase chain reaction and sequenced using Illumina MiSeq. The relationships between fecal bacteria and clinical phenotypes were analyzed using the EzBioCloud database and 16S microbiome pipeline.
Results
The alpha-diversity of fecal bacteria was significantly lower in UC and CD (P<0.05) compared to that in HC. Bacterial community compositions in UC and CD were significantly different from that of HC according to Bray-Curtis dissimilarities, and there was also a difference between community composition in UC and CD (P=0.01). In UC, alpha-diversity was further decreased when the disease was more severe and the extent of disease was greater, and community composition significantly differed depending on the extent of the disease. We identified 9 biomarkers of severity and 6 biomarkers of the extent of UC. We also identified 5 biomarkers of active disease and 3 biomarkers of ileocolonic involvement in CD. Lachnospiraceae and Ruminococcus gnavus were biomarkers for better prognosis in CD.
Conclusions
The fecal microbiota profiles of IBD patients were different from those of HC, and several bacterial taxa may be used as biomarkers to determine disease phenotypes and prognosis. These data may also help discover new therapeutic targets for IBD.

Keyword

Inflammatory bowel disease; Microbiota; Biomarkers; Phenotype; Prognosis

Figure

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  Fig. 1. Diversity of fecal microbiota in a HC, UC patients, and CD patients. (A) Chao 1 index, (B) Shannon index, and (C) beta diversity based on Bray-Curtis dissimilarities. Both richness and diversity were significantly lower in inflammatory bowel disease patients compared with HC, and Shannon diversity index was significantly lower in CD compared with UC. Post hoc analyses using pair-wise comparisons showed that 3 groups were significantly different from each other (HC vs. UC, P=0.001; HC vs. CD, P=0.001; UC vs. CD, P=0.001). HC, healthy control individuals; UC, ulcerative colitis; CD, Crohn’s disease.

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  Fig. 2. Diversity of fecal microbiota in ulcerative colitis (UC) patients according to disease severity (A) and disease extent (B). Alpha diversity decreased as the disease severity and extent deteriorated.

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  Fig. 3. Composition of fecal microbiota in HC, UC patients, and CD patients at the phylum (A), genus (B), and species (C) level. Compared to HC and UC patients, CD patients had significantly higher abundances of the phylum Proteobacteria, the genus Escherichia, and the species Escherichia coli. HC, healthy control individuals; UC, ulcerative colitis; CD, Crohn’s disease.

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  Fig. 4. Taxa list according to linear discriminate analysis values determined from comparisons between HC and UC patients (A), and between HC and CD patients (B). Effect size estimation analysis identified 9 bacterial taxa that were significantly more abundant in UC patients than HC (A), and 14 bacterial taxa that were significantly more abundant in CD patients than HC. HC, healthy control individuals; UC, ulcerative colitis; CD, Crohn’s disease.

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  Fig. 5. Taxa list according to linear discriminate analysis values determined from comparisons according to disease severity and extent in ulcerative colitis (UC) patients. Comparisons between moderate to severe and mild UC (A), between moderate to severe UC and remission (B), and between left sided or extensive UC and proctitis (C). Some bacterial taxa (red color) were identified as potential biomarkers for moderate to severe UC compared to mild UC (A), and remission status (B). Several bacterial taxa (red color) were found to be associated with left sided or extensive UC (C).

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  Fig. 6. Taxa list according to linear discriminate analysis values determined from comparisons according to disease severity and extent in Crohn’s disease (CD) patients. Comparisons between remission and active CD (A) and between ileocolonic and small bowel CD (B). Some bacterial taxa (red color) were identified as possible biomarkers for active disease status, compared to remission status (A). Several bacterial taxa (red color) were identified as possible biomarkers for ileocolonic involvement, compared to small bowel involvement only (B).

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  Fig. 7. Relative abundance of particular taxa in Crohn’s disease (CD) patients based on prognosis. (A) Lachnospiraceae and (B) Ruminococcus gnavus. Better prognosis is defined as patients who did not consume biologic agents including anti-tumor necrosis factor (TNF)-α agents or surgical treatment after fecal sampling and worse prognosis is defined as patients who either were administered biologic agents including anti-TNF-α agents or required surgical treatment after fecal sampling (n=9). Lachnospiraceae and R. gnavus were significantly more abundant in the better prognosis group compared to the worse prognosis group.

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