Metabolic surgery profoundly influences gut microbial–host metabolic cross-talk
- Jia V Li1,2,
- Hutan Ashrafian2,3,
- Marco Bueter3,4,
- James Kinross1,2,
- Caroline Sands1,
- Carel W le Roux3,
- Stephen R Bloom3,
- Ara Darzi2,
- Thanos Athanasiou2,
- Julian R Marchesi5,
- Jeremy K Nicholson1,2,
- Elaine Holmes1
- 1Section of Biomolecular Medicine, Imperial College London, London, UK
- 2Section of Biosurgery & Surgical Technology, Department of Surgery and Cancer, Imperial College London, London, UK
- 3Section of Investigative Medicine, Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, Faculty of Medicine, Imperial College London, London, UK
- 4Department of Surgery, Division of Visceral and Transplantation Surgery, University Hospital, Zürich, Switzerland
- 5School of Biosciences, Cardiff University, Cardiff, UK
- Correspondence to Professor Elaine Holmes, Department of Surgery and Cancer, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, UK; Dr Julian R Marchesi, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AT, UK;
Contributors HA and TA designed research; HA and MB performed animal experiments and clinical measurement; JVL performed NMR analyses; JRM and JVL performed microbiomic and bioinformatic analyses; JVL, JRM, HA, CS, JKN, CWlR, SRB, AD, TA and EH analysed and interpreted data; JVL, JRM, HA, JK, JKN, TA and EH wrote the paper.
- Revised 16 March 2011
- Accepted 17 March 2011
- Published Online First 14 May 2011
Background and aims Bariatric surgery is increasingly performed worldwide to treat morbid obesity and is also known as metabolic surgery to reflect its beneficial metabolic effects especially with respect to improvement in type 2 diabetes. Understanding surgical weight loss mechanisms and metabolic modulation is required to enhance patient benefits and operative outcomes.
Methods The authors applied a parallel and statistically integrated bacterial profiling and metabonomic approach to characterise Roux-en-Y gastric bypass (RYGB) effects in a non-obese rat model.
Results Substantial shifts of the main gut phyla towards higher concentrations of Proteobacteria (52-fold), specifically Enterobacter hormaechei, are shown. Low concentrations of Firmicutes (4.5-fold) and Bacteroidetes (twofold) in comparison with sham-operated rats were also found. Faecal extraction studies revealed a decrease in faecal bile acids and a shift from protein degradation to putrefaction through decreased faecal tyrosine with concomitant increases in faecal putrescine and diaminoethane. Decreased urinary amines and cresols were found and indices of modulated energy metabolism were demonstrated after RYGB, including decreased urinary succinate, 2-oxoglutarate, citrate and fumarate. These changes could also indicate renal tubular acidosis, which is associated with increased flux of mitochondrial tricarboxylic acid cycle intermediates. A surgically induced effect on the gut–brain–liver metabolic axis is inferred from modulated faecal γ-aminobutyric acid and glutamate.
Conclusion This profound co-dependence of mammalian and microbial metabolism, which is systematically altered after RYGB surgery, suggests that RYGB exerts local and global metabolic effects. The effect of RYGB surgery on the host metabolic–microbial cross-talk augments our understanding of the metabolic phenotype of bariatric procedures and can facilitate enhanced treatments for obesity-related diseases.
- Bariatric surgery
- NMR spectroscopy
- bile acid
- morbid obesity
- nuclear magnetic resonance
See Commentary, p 1166
Linked article 242503.
JVL and HA contributed equally to this work.
Funding This study received financial support from the Imperial College London Junior research fellowship to JVL and from the Wellcome Trust Research Training Fellowship to HA. We are grateful for support from the NIHR Biomedical Research Centre Funding Scheme.
Competing interests None.
Ethics approval All animal experiments were approved by Charing Cross Research Ethics Committee, London, UK.
Provenance and peer review Not commissioned; externally peer reviewed.