title: Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Biomolecular, Imperial College London, South Kensington, London SW7 2AZ, UK.
authors.forename: Jia V
authors.initials: JV
authors.lastname: Li
authors.forename: Hutan
authors.initials: H
authors.lastname: Ashrafian
authors.forename: Marco
authors.initials: M
authors.lastname: Bueter
authors.forename: James
authors.initials: J
authors.lastname: Kinross
authors.forename: Caroline
authors.initials: C
authors.lastname: Sands
authors.forename: Carel W
authors.initials: CW
authors.lastname: le Roux
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.forename: Ara
authors.initials: A
authors.lastname: Darzi
authors.forename: Thanos
authors.initials: T
authors.lastname: Athanasiou
authors.forename: Julian R
authors.initials: JR
authors.lastname: Marchesi
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D004435:Eating / Q000502:physiology; D005243:Feces / Q000737:chemistry; D015390:Gastric Bypass; D041981:Gastrointestinal Tract / Q000473:pathology; D054884:Host-Pathogen Interactions; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D054892:Metagenome; D018377:Neurotransmitter Agents / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014630:Vagus Nerve / Q000503:physiopathology; D015431:Weight Loss / Q000502:physiology
chemical_list: D001647:Bile Acids and Salts; D018377:Neurotransmitter Agents