Change in Gut Flora May Drive Surgical Weight Loss
By Charles Bankhead, Staff Writer, MedPage Today, Published: March 27, 2013
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Results of a study in rats and mice suggest that gastric bypass surgery alters gut microflora and that alteration acts as a weight-loss mechanism independent of caloric restriction.
Fecal samples obtained before and after Roux-en-Y gastric bypass (RYGB) surgery showed a rapid and sustained increase in Gammaproteobacteria (primarily Escherichia) and Verrucomicrobia (Akkermansia). The change in gut microbiota occurred independent of weight loss and caloric restriction and was evident across the entire gastrointestinal tract.
Sham bariatric surgery did not induce the changes in microbiota, but transfer of gut microbiota from RYGB-treated mice to untreated mice resulted in weight loss and a reduction in fat mass in the untreated animals, according to an article published online in Science Translational Medicine.
"These findings provide the first empirical support for the claim that changes in the gut microbiota contribute to reduced host weight and adiposity after RYGB surgery," Lee M. Kaplan, MD, PhD, of Massachusetts General Hospital in Boston, and co-authors concluded.
The shift in gut microbiota mirrors those observed in humans and rats following bariatric surgery.
"It is clear that RYGB produces unique selective pressures to modulate community structure that is not merely a reversion to a community seen in the lean, normal chow-fed state," Kaplan and colleagues added.
RYGB can induce sustained reductions of 65% to 75% of excess body weight and fat mass, which are associated with improved glucose homeostasis and amelioration of other risk factors for diabetes and cardiovascular disease.
Initial research suggested the weight loss and metabolic changes resulted primarily from caloric restriction and malabsorption. More recent studies have produced evidence that RYGB alters the basic physiology of energy balance and metabolism, although mechanistic evidence to explain the observations has been lacking, the authors noted in their introduction.
Several recent studies have documented changes in fecal microbial profiles in humans and rats after RYGB. The relative contributions of various factors have remained unclear, including alterations in the gastrointestinal tract, direct effects of the surgery, and decreased weight and caloric intake that occurs after RYGB. Moreover, the rapidity and stability of the changes have yet to be determined, as well as whether the changes are limited to the distal gut, the authors continued.
To address some of the unresolved issues about the effects of RYGB, Kaplan and colleagues performed a series of experiments in mice. Diet-induced obese mice underwent RYGB and lost 29% of initial body weight within 3 weeks. Mice in a control group underwent sham surgery and returned to presurgical weight within 2 to 3 weeks.
A subgroup of control mice were fed 25% fewer calories to match the weight loss of the RYGB mice. Consistent with previous studies, the RYGB mice had preferential loss of fat mass and preservation of lean mass as compared with the control group.
To study the effects of RYGB on distal gut microbiota, investigators performed ribosomal RNA gene sequencing on fecal samples before surgery and weekly for 3 months after surgery in the RYGB, sham-operated, and weight-matched groups of animals. RYGB dramatically altered the gut microbiota within a week, and the changes progressed for about 5 weeks before stabilizing.
Sham-operated and weight-matched animals did not differ significantly in terms of gut microbiota.
The concentration of Enterobacteriales increased during the first 2 weeks after RYGB, and the Verrucomicrobiales increased more than 10,000-fold as compared with baseline. In contrast, Verrucomicrobiales increased modestly (threefold versus baseline) in the sham-operated and weight-matched animals.
Detailed analyses of fecal samples revealed variations in the relative abundance of bacterial taxa and phylotypes among the RYGB, sham-operated, and weight-matched mice. The RYGB microbiota were enriched at the phylum level with Bacteroidetes, Verrucomicrobia, and Proteobacteria and at the genus level (Alistipes, Akkermansia, and Escherichia). In general, the changes were consistent throughout the gastrointestinal tract of the RYGB animals.
Previous studies had shown that gut microbiota can affect adiposity and glucose homeostasis. Building on those results, Kaplan and colleagues inoculated lean, germ-free mice with cecal contents of RYGB donors, sham-operated donors, and weight-matched donors.
During a 2-week colonization period, animals that received inoculates from the RYGB mice lost 5% of body weight (P<0.05), whereas the control animals had no change in weight.
Food intake of sham-operated animals decreased in comparison with uninoculated germ-free animals (P<0.01). Food intake in the RYGB animals increased relative to the sham-operated and weight-matched control animals. Nonetheless, the sham-operated and weight-matched animals had a significantly greater fat mass compared with the RYGB group (P<0.05) and compared with uninoculated germ-free animals (P<0.01).
Given that increases in Gammaproteobacteria have been documented in humans, rats, and mice after RYGB, the authors speculated that Gammaproteobacteria "could be a key contributor to regulating host metabolic outcomes after surgery."
Escherichia was the most highly enriched genus in the mouse RYGB model and comprises several pathogenic strains associated with metabolic syndrome, obesity, and insulin resistance, as well as nonpathogenic strains that have been used in probiotic treatment of gastrointestinal inflammation. The authors speculated that the "specific Escherichia population enriched after RYGB may have some beneficial role in driving host metabolic improvements after surgery."
The persistent increase in Verrucomicrobium Akkermansia after RYGB may suggest a "substantial role in regulating host adiposity and weight loss," they added.