Gut microbiome signatures reflect different subtypes of irritable bowel syndrome

ABSTRACT

Irritable bowel syndrome (IBS) is a heterogeneous condition with multifactorial pathogenesis. We studied deeply phenotyped individuals with microbiota sequencing enrolled in the American Gut Project. The IBS subjects were matched by age, gender, body mass index, geography, and dietary patterns with non-IBS controls. A total of 942 subjects with IBS-Diarrhea (IBS-D), IBS-Constipation (IBS-C), unclassified IBS (IBS-U), and 942 non-IBS controls were included. We compared taxonomic and functional composition of gut microbiota based on 16S sequencing data and linked them with clinical characteristics and dietary factors. Subjects with IBS-D or IBS-U but not IBS-C showed significantly reduced bacterial diversity (Shannon; p < .01). Distinct bacterial signatures were associated with different IBS subtypes, and the related functional changes were related to IBS pathogenesis, such as the increased hydrogen sulfide production pathway in IBS-D and the increased palmitoleate biosynthesis pathway in IBS-C. IBS subjects with depression showed lower abundance of Bifidobacterium, Sutterella, Butyricimonas and higher abundance of Proteus than those without depression. The relative abundance of microbial short-chain fatty acid production pathways was significantly lower in IBS patients with depression than those without depression in all three subtypes. Female, younger age in IBS-D, and older age in IBS-C were associated with more severe microbiota dysbiosis, and distinct dietary factors had significant effects on the gut microbiota in different IBS subtypes. Our analysis identified the compositional uniqueness of gut microbiota in different IBS subtypes. Distinct associations of the gut microbiota with depression in IBS provide insights into shared pathways in disease pathogenesis. These findings highlight the importance of personalized gut microbiome modulation approaches in different subtypes for optimal therapeutic effects.

KEYWORDS:

• Irritable bowel syndrome
• gut microbiome
• subtype
• diet
• depression

Author contributions

QS conceived and designed the study and took responsibility for the integrity of the data and preparation of manuscript. HMT, QL, YKY, JWYM, and FKLC critically revised the manuscript for important intellectual content of microbiome and gastroenterology. SC Ng contributed to the study guidance and manuscript writing. All authors gave final approval for the version to be published.

Disclosure statement

FKLC and SCN are the scientific co-founders and sit on the board of Directors of GenieBiome Ltd. SCN has served as an advisory board member for Pfizer, Ferring, Janssen, and Abbvie and a speaker for Ferring, Tillotts, Menarini, Janssen, Abbvie, and Takeda. She has received research grants from Olympus, Ferring, and Abbvie. FKLC has served as an advisor and lecture speaker for Eisai Co. Ltd., AstraZeneca, Pfizer Inc., Takeda Pharmaceutical Co., and Takeda (China) Holdings Co. Ltd. All other co-authors have no conflict of interest.

Data availability statement

Sequences and metadata are available from the European Bioinformatics Institute (EBI) database under project ID: PRJEB11419 (https://www.ebi.ac.uk/ena/browser/view/PRJEB11419).

Code availability

Source code for the case–control matching algorithms was from a previous study¹². Code for statistical analyses can be obtained by reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2022.2157697

Additional information

Funding

These authors are partially supported by InnoHK, the Government of Hong Kong, Special Administrative Region of the People’s Republic of China. SCN is also supported by the Croucher Senior Medical Research Fellowship.