Bariatric Surgery Alters Gene Expression

CHICAGO – As Roux-en-Y bariatric surgery changes eating habits and transforms a patient's gut, different levels of gene expression that emerge post-surgery may provide clues for new type 2 diabetes treatments, researchers suggested here.

In preliminary findings, Margaret Stefater, MD, PhD, a fellow at Boston Children's Hospital/Harvard Medical School, reported that intestinal genetic fingerprinting using gene-chip microarray technology may predict clinical outcomes, with the degree of those outcomes tied to intestinal gene expression signatures.

Stefater reported on 19 patients during a press conference at ENDO 2018, remarking that gene expression changes in these patients post-surgery seem to indicate that the changes could predict outcomes at 1 year.

Roux-en-Y bariatric surgery leads to a remission of diabetes for as many as 80% of patients who undergo the radical surgery, she noted. "The intestine appears to be a key organ underlying the effects of Roux-en-Y surgery," she said.

The surgery bypasses the stomach and creates a small pouch that replaces the stomach for food storage and digestion. Stefater said Roux-en-Y causes a phenomenon she refers to as the "hungry intestine," wherein the surgery results in an increased workload and remodeling of the gut, and uses glucose, cholesterol, and amino acids as fuels to accomplish this.

In the study, researchers performed biopsies at the time of surgery, and then again at 1, 6 and 12 months post-surgery. Stefater reported on the project at the 6-month time point; 19 of the 32 study patients were evaluable for this analysis.

She told MedPage Today that her research is continuing the process of calculating the genetic expression changes observed with the gene-chip microarray, but there appears to be overexpression of genes in inflammatory and metabolic pathways.

While more weight loss was seen at 6 months versus 1 month post-surgery, Roux-limb gene expression profiles that compared differentially expressed genes at the two time points revealed a 40% overlap.

"Gene expression signatures in the intestine can predict both concurrent and future improvement in glucose metabolism and other clinical outcomes," Stefater said. "Our data highlight that the intestine may be an important therapeutic target for patients with type 2 diabetes."

Click here for video comments from study authors and discussants at ENDO 2018.

Changes in gene expression occurred early, the researchers noted, and in diabetic patients these changes were mirrored by a reduction in HbA1c at 1 month (P<0.05).

Commenting on the study, Mitchell Roslin, MD, chief of obesity surgery at Lenox Hill Hospital in New York City, told MedPage Today, "We have noticed this type of gene expression change among our patients undergoing both Roux-en-Y and 'sleeve' procedure. These surgeries change the gut environment, and there are genetic responses to those changes in food storage and gastric emptying."

He said that whether scientists will be able to exploit the findings and create a medication that can replicate the same beneficial effects will "not be an easy task."

Roslin said there are probably 15 to 20 different mechanisms of action involved in these gut changes impacting processes such as insulin resistance. "It most likely involves a combination of effects," he said, "including the type of surgery and what the patients eat after the surgery is complete."

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