A gut-check for answers

New study reveals why the gastrointestinal microbiota affects disease

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GOTHENBURG, Sweden—Several studies in recent years have found evidence that the unique mix of bacteria in an individual's gut is associated with their vulnerability to various health disorders. Until now, however, scientists had not pinpointed the particular mechanisms through which different kinds of gut bacteria affect health.
A new study published in Molecular Systems Biology has shed light on how it works. Research conducted at Chalmers University of Technology, the Royal Institute of Technology and the University of Gothenburg in Sweden found that gut bacteria regulate a key antioxidant found in every human cell. Deficiencies of that antioxidant, glutathione, contribute to oxidative stress, which plays an important role in several lifestyle diseases.
The goal of the study, first author Adil Mardinoglu tells DDNews, was to investigate “the global metabolic differences between two mice that could be directly linked to the presence of the bacteria in mice.” Mardinoglu, an assistant professor at Chalmers, and other researchers accomplished this by creating a generic map of mouse metabolism and tissue-specific computer models for major mouse tissues. They found that the microbiota in the small intestine consumed glycine, which is one of the three amino acids required for the synthesis of glutathione.
Glutathione plays a vital role in the human immune system, enabling nutrient metabolism and regulation of other important cellular dynamics. It is considered to be one of the body’s most powerful antioxidants and the main detoxifying agent in the body. A very small protein, glutathione is produced inside the cells from three amino acids that are obtained either from food or supplementation. Deficiencies of glutathione in the body are known to contribute to oxidative stress.
“Some bacteria in our gut consume glycine, which is required for the synthesis of the glutathione, and imbalances in the composition of the bacteria may lead to the progression of the chronic diseases,” said Mardinoglu.
While Mardinoglu’s study was the first to reveal the role of gut bacteria in regulating glutathione, it has long been known that the makeup of gut microbiota is an important factor in the development of various human disorders, including obesity, type 2 diabetes, atherosclerosis, non-alcoholic fatty liver disease and even malnutrition. Increasing awareness of these dynamics has led researchers to study more closely the interactions between gut microbiota of an individual, the host tissues of the gastrointestinal tract and diet. Independent studies in the past have found that imbalances in the plasma level of glycine as well as other amino acids have been shown to exist in obesity, type 2 diabetes and non-alcoholic fatty liver disease.
Chalmers professor Jens Nielsen noted in a public statement about the new findings that previous studies have found lower plasma levels of glycine in all subjects with certain diseases when compared to the healthy subjects. “In this context, it may be of interest to study the microbial amino acids in the human gut in relation to their potential role in the development of such metabolism-related disorders,” he said.
Researchers working with Mardinoglu confirmed the initial results of the computer-based simulations they used by measuring the level of amino acids in the portal vein of the mice. They also found evidence that gut microbiota regulates glutathione metabolism in the liver and colon as well as in the small intestine. This was indicated by lower levels of glycine that were observed in those organs.
Greater knowledge of how gut microbiota affects health could eventually make it feasible for people to adjust their eating habits in order to create a gut microbiota that is less vulnerable to disease. Nielson suggests that dietary products might eventually be developed for this purpose.
“The discovery that the bacteria in our small intestine consume glycine and regulate glutathione metabolism may led to the development of food products that can deliver beneficial bacteria (probiotics) to the gut,” he said.
Mardinoglu tells DDNews that before any such products are developed—and one could assume pharmaceutical or biologics could also be developed that might achieve good results—it will be necessary to make more progress identifying gut bacteria and studying more thoroughly the diet required for maintaining the best biomass to maintain a healthy gut microbiome.
“The next step is the identification of the bacteria consuming certain amino acids to see how their abundance changes during the development of the metabolism related disorders,” he says.

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