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Manipulating microbes could be an alternative to bariatric surgery

Manipulating microbes - The researchers observed that the impact of surgery is not limited to faecal communities; mucosal communities are altered as well.

Researchers generally agree that genetic and gut microbiome composition and activity are important factors in determining who has and who does not have obesity. As interest and understanding of the human microbiome increases, researchers are increasingly looking to the gut for answers that can lead to new, more effective diagnostics and therapies.

The trillions of microbes in the human gut perform a vast range of critical functions in the body and have even been implicated in mood and behaviour. Among microbes' critical responsibilities are the micro-management of nutrients in the food we digest - one of the reasons for their central role in the regulation of body weight.

In a study, ‘Temporospatial shifts in the human gut microbiome and metabolome after gastric bypass surgery’,published in npj Biofilms and Microbiomes, Arizona State University (ASU) researcher Zehra Esra Ilhan, ASU Biodesign professor Rosa Krajmalnik-Brown, and researchers from Mayo Clinic and Pacific Northwest National Laboratory, have taken another step in understanding how the gut changes after Roux-en-Y gastric bypass surgery.

Zehra Esra Ilhan
Zehra Esra Ilhan

"Our findings highlight the importance of changes in mucosal and faecal microbiomes that are reflected on gut metabolism after surgery," said Ilhan. “The microbial changes after surgery corresponded to persistent changes in faecal fermentation and bile acid metabolism, both of which are associated with improved metabolic outcomes."

In addition to the expected weight reduction and improvement in obesity-related comorbidities after gastric bypass surgery, the researchers observed that the impact of surgery is not limited to faecal communities; mucosal communities are altered as well. Changes in the microbiome were linked to increased concentrations of branched-chain fatty acids (amino acid fermentation products) and an overall decrease in primary and secondary bile acid concentrations in faecal samples. Bile is an alkaline fluid that aids digestion.

"Previous bariatric surgery-microbiome studies in humans relied largely on faecal samples because sampling through the intestinal mucosal membrane requires an invasive procedure," said Ilhan, lead researcher for the study.

At the time of the study, Ilhan was a doctoral student in Krajmalnik-Brown's lab. She is currently conducting research at INRAE-French National Institute for Agriculture, Food and Environment.

"The mucus membrane is a critically important site for host-microbe interactions. We understood that with fecal sampling, we had an underrepresented picture of how the mucosal communities actively interact with host immune system and epithelial cells," added Ilhan.

Although gastric bypass surgery has been successful for many patients suffering from morbid obesity, it is a serious, invasive procedure that is not without risk and expense. In addition, some patients regain the weight they have lost, perhaps because they lack the favourable microbes necessary for permanent weight loss.

"Understanding the microbial behaviour in the gut could potentially lead to a creating a probiotic that could replace surgery - or an improved indicator to identify the best candidates for surgery and sustained weight loss," said Krajmalnik-Brown, professor in the ASU School of Sustainable Engineering and Built Environment and faculty in the School of Life Sciences. At the Biodesign Institute, she practices as part of the Swette Center for Environmental Biotechnology. Krajmalnik-Brown is also known for her research into the role of the microbiome in those with autistic spectrum disorder.

In the longitudinal study, subjects provided faecal samples and rectal mucosal samples. The rectal mucosal samples were collected via un-sedated flexible sigmoidoscopy at baseline, and again at 12 months post-gastric bypass surgery. Researchers analysed microbial DNA that was extracted from the faecal and mucosal samples. Faecal metabolites were analysed using high-throughput metabolomics approaches.

A tell-tale indicator of pathology in obese patients has been found in the gut, where a markedly lower diversity of microbial communities is observed. A high diversity of gut microbes is essential to good health.

In 2009, Krajmalnik-Brown's research team showed for the first time that gastric bypass surgery produced profound changes in the composition of microbial communities in the gut. The gut flora of post-surgical gastric bypass patients showed a marked difference from obese and normal weight patients.

In a 2017 study, the team took another step by comparing how microbes and the metabolome (the metabolome is the total number of metabolites present within an organism, cell or tissue) change after gastric bypass surgery and lap band surgery.

The 2017 study demonstrated that gastric bypass surgery caused a dramatic reorganisation of the gut, which increases microbial diversity. Changes in the gut microbiota related to laparoscopic adjustable gastric banding were mild and accompanying weight loss was less pronounced. Earlier studies have demonstrated that fat is reduced and weight loss triggered when germ-free mice receive a faecal transplant from mice who had undergone gastric bypass surgery.

Krajmalnik-Brown's team is currently working on a project funded by the National Institutes of Health in which the main goal is to quantify the contribution of the microbiome to the host energy balance. This project is intended to move the field from associations to causality and help identify how microbes and metabolites can fight obesity.

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R01DK090379.

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