Distinctive patterns of sulfide- and butyrate-metabolizing bacteria after bariatric surgery: potential implications for colorectal cancer risk

ABSTRACT

Despite improved cardiometabolic outcomes following bariatric surgery, its long-term impact on colorectal cancer (CRC) risk remains uncertain. In parallel, the influence of bariatric surgery on the host microbiome and relationships with disease outcomes is beginning to be appreciated. Therefore, we investigated the impact of Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on the patterns of sulfide-reducing and butyrate-producing bacteria, which are hypothesized to modulate CRC risk after bariatric surgery. In this single-center, cross-sectional study, we included 15 pre-surgery subjects with severe obesity and patients who are at a median (range) of 25.6 (9.9–46.5) months after RYGB (n = 16) or VSG (n = 10). The DNA abundance of fecal bacteria and enzymes involved in butyrate and sulfide metabolism were identified using metagenomic sequencing. Differences between pre-surgery and post-RYGB or post-VSG cohorts were quantified using the linear discriminant analysis (LDA) effect size (LEfSe) method. Our sample was predominantly female (87%) with a median (range) age of 46 (23–71) years. Post-RYGB and post-VSG patients had a higher DNA abundance of fecal sulfide-reducing bacteria than pre-surgery controls (LDA = 1.3–4.4, p < .05). The most significant enrichments were for fecal E. coli, Acidaminococcus and A. finegoldii after RYGB, and for A. finegoldii, S. vestibularis, V. parvula after VSG. As for butyrate-producing bacteria, R. faecis was more abundant, whereas B. dentium and A. hardus were lower post-RYGB vs. pre-surgery. B. dentium was also lower in post-VSG vs. pre-surgery. Consistent with these findings, our analysis showed a greater enrichment of sulfide-reducing enzymes after bariatric surgery, especially RYGB, vs. pre-surgery. The DNA abundance of butyrate-producing enzymes was lower post-RYGB. In conclusion, the two most used bariatric surgeries, RYGB and VSG, are associated with microbiome patterns that are potentially implicated in CRC risk. Future studies are needed to validate and understand the impact of these microbiome changes on CRC risk after bariatric surgery.

KEYWORDS:

• Bariatric
• microbiome
• sulfide-reducing
• butyrate
• colorectal cancer

Abbreviations

CRC	=	Colorectal cancer
EC	=	Enzyme commission
HEI-2010	=	Healthy Eating Index-2010
LDA	=	Linear discriminant analysis
RYGB	=	Roux-en-Y gastric bypass
SD	=	Standard Deviation
VSG	=	Vertical sleeve gastrectomy

Acknowledgments

H.H. was involved in study conception, sample collection, design, interpretation of data, manuscript drafting, and critical revision. M. P., C. W., and A.W. analyzed the data and critically revised the manuscript. The above authors had full access to all the data in the study and take responsibility for data integrity and data analysis accuracy. E. G., M. W., B. N., S. N. were involved in patient recruitment, biospecimens transport and storage, and critical review of the manuscript. J. Z and F. C performed the SCFA analysis and critical review of the manuscript. S. C. and M. B. were involved in the study design, data interpretation, and critical revision of the manuscript. All authors gave final approval of the submitted manuscript and take responsibility for the integrity of the work. Finally, we would like to thank Dr. Arsheya Patel for helping with patient recruitment in the study

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Our detailed methods are described in detail in this paper. Our investigators will make analytical files available to researchers for noncommercial purposes https://doi.org/10.5281/zenodo.8326652.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2255345

Additional information

Funding

This work was supported by The Ohio State University Early Investigator Award and the Molecular Carcinogenesis and Chemoprevention Program seed grant from The Ohio State University Comprehensive Cancer Center. The SCFA analysis was supported by National Institute of General Medical Science under Award Number R35GM133510.