Becky McCall

September 30, 2015

STOCKHOLM — In obese patients with type 2 diabetes undergoing bariatric surgery, gastric bypass induces more beneficial changes in composition of the gut microbiota than sleeve gastrectomy, according to new research presented at the recent European Association for the Study of Diabetes (EASD) 2015 Meeting.

Bypass also increases the capacity of gut microbiota to produce beneficial short-chain fatty acids and was more closely associated with diabetes remission.

The study aimed to assess the impact of the two types of bariatric surgery on gut microbiota among those who achieved type 2 diabetes remission at 1 year after the operation.

Lead investigator Rinki Murphy, MD, a diabetologist from the University of Auckland, New Zealand, told Medscape Medical News: "We found that there were marked changes in the gut microbiota in opposite directions [between the two procedures], and consequently the function of the microbiota seemed to go in a metabolically more favorable direction after bypass as opposed to sleeve gastrectomy."

She added that they found similar changes in diet and weight between the two procedures but also that "sleeve gastrectomy was not as beneficial with respect to the extent of diabetes remission."

Although early days, the results could one day lead to the development of probiotics to help treat obesity and type 2 diabetes, she suggested.

Gastric Bypass vs Sleeve Gastrectomy

The choice of which type of bariatric surgery is most suitable for type 2 diabetic patients remains controversial.

Dr Murphy explained that bypass tends to be slightly superior to sleeve gastrectomy, but the reasons for this remain unclear. "One possibility could be the change in gut microbiota."

The randomized, blinded trial aimed to shed some light on this. Gastric bypass was compared with sleeve gastrectomy in 110 obese patients with type 2 diabetes.

A subanalysis looked at gut microbiota and gut hormones in 52 of the patients, and the results of the first 14 patients in this subgroup (seven of whom underwent bypass and seven sleeve gastrectomy) were presented by Dr Murphy at the meeting.

Patients were assessed immediately presurgery and at 1 year postsurgery. Medication use, 5-day food diaries, satiety questionnaires, body composition, and resting energy expenditure were all recorded. Frequently sampled oral glucose tolerance tests, HbA1c, lipids, gut hormones, inflammatory markers, and stool samples were also taken.

Whole-genome shotgun sequencing enabled the researchers to determine gene function as well as genetic sequences present, which are the key to "fingerprinting" the types of bacteria found, Dr Murphy explained.

Changes in Gut Microbiota and Gene Function in Remission

Results across all 14 patients showed there was an increase in abundance of some "good" gut bacteria and a reduction in abundance of some "bad" bacteria after sleeve gastrectomy compared with a decrease and increase respectively following bypass, said Dr Murphy, but, on balance, the gut microbiota were overall more favorable following bypass.

Five patients out of seven in each surgical group were in type 2 diabetes remission 1 year postprocedure, with no requirement for glucose-lowering therapy.

"But the degree of improvement obtained after gastric bypass was significantly greater than after sleeve gastrectomy," Dr Murphy noted.

In patients who had a bypass, four achieved full remission (HbA1c ≤ 5.6%) and one achieved partial remission (HbA1c ≤ 6.5%). In those who received sleeve gastrectomy, one achieved full remission and four achieved partial remission after 1 year.

"The only organism that was more commonly in abundance was Roseburia intestinalis, which increased after both procedures [but more so after bypass]. Low levels of these bacteria have been associated with type 2 diabetes in two large meta-genomewide-association studies," added Dr Murphy.

But gene-function changes in those with diabetes remission were markedly different after the two procedures: they were greater after gastric bypass, corresponding to increased microbial diversity, than after sleeve gastrectomy.

The gut-microbiota functions were also numerically greater after the bypass and significantly different from those after sleeve gastrectomy.

"After the bypass there was a preference for bacterial-function changes that relate to short-chain fatty-acid production and could be beneficial to the individual in terms of satiety, among other things," Dr Murphy explained.

"More motile bacteria were also seen, and these have been seen more frequently among leaner people," she added.

Similar reductions in body weight were seen between the two surgical procedures, at a 27.4-kg loss after gastric bypass vs a 23.5-kg loss following sleeve gastrectomy (P = .48), body mass index (BMI) reductions of 9.9 vs 7.6 (P = .29) and resting energy expenditure of 240 kcal vs 198 kcal (P = .57). respectively.

Findings May Lead to Nonsurgical Probiotic Treatment

Dr Murphy stressed, however, that, at this early stage, it is unknown as to which, if any, gut microbiota changes resulting from the different surgery types are causally linked with the metabolic benefits seen.

Looking at the bigger picture, she remarked that understanding the changes achieved through surgery might help researchers to achieve similar changes nonsurgically.

"This is one step in the direction of finding out what changes happen to the microbiota, and eventually, if we discover the exact strains of the good guys, the hope is that we may be able to isolate and synthesize these into a probiotic."

Fredrik Bäckhed, PhD, of University of Gothenburg, Sweden, a researcher with a special interest in the microbiota of metabolic diseases, said this was an interesting study but that "the reported differences in the microbiota following the two weight-reduction surgeries are very surprising, as the outcome for the patents is similar."

He added that it will be important "to confirm the findings in the full cohort."

Dr Murphy has declared no relevant financial relationships. Dr Bäckhed is founder and shareholder of Metabogen.

European Association for the Study of Diabetes 2015 Meeting; Stockholm, Sweden. Abstract 221, presented September 18, 2015.

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