Gut microbiota regulates antioxidant metabolism

Study results may elucidate how bacteria play a role in the metabolic processes involved in the development of obesity, type 2 diabetes, non-alcoholic fatty liver disease and malnutrition

A recently published study shows that gut microbiota regulates the glutathione and amino acid metabolism of the host. Glutathione is a key antioxidant, found in every cell in our body. Deficiency of glutathione contributes to oxidative stress, which plays a major role in several lifestyle diseases.

The functional output and diversity of gut microbiota are important modulators for the development of various human disorders. Obesity, type 2 diabetes, atherosclerosis, non-alcoholic fatty liver disease and malnutrition have all been associated with an imbalance in the human gut microbiota. Hence, the interactions between the gut microbiota, host tissues of the gastrointestinal tract and other peripheral tissues, as well as diet, are known to be highly relevant for the health of the host.

In a recent paper published in Molecular Systems Biology, researchers at Chalmers University of Technology, the Royal Institute of Technology and the University of Gothenburg in Sweden revealed that the gut microbiota regulates the glutathione and amino acid metabolism of the host.

The study shows how a novel integrative approach can be used to reveal the metabolic differences between germ-free and conventionally raised mice through a combination of proteomics, transcriptomics and metabolomics data, as well as tissue-specific metabolic modelling.

Glutathione is our body's most powerful antioxidant and the main detoxifying agent in the body. It plays a vital role in enabling the immune system, nutrient metabolism and regulation of other important cellular events. Glutathione is a very small protein, produced inside the cells from three amino acids ultimately obtained from our food or supplementation. Glutathione deficiency contributes to oxidative stress, which plays a major role in the mechanisms of above mentioned complex disorders.

In the study, a generic map of mouse metabolism was created, and tissue-specific computer models for major mouse tissues were generated. By integrating high throughput experimental data, the researchers found that the microbiota in the small intestine consumes glycine, which is one of the three amino acids required for the synthesis of glutathione.

To confirm the results of the computer-based simulations, the level of the amino acids in the portal vein of the mice was measured. Moreover, a lower level of glycine was observed in the liver and colon tissues, which indicates that the gut microbiota regulates glutathione metabolism, not only in the small intestine but also in the liver and the colon.

'Some bacteria in our gut consume glycine, which is required for the synthesis of glutathione, and imbalances in the composition of the bacteria may lead to the progression of the chronic diseases,' says Chalmers researcher Adil Mardinoglu, first author of the paper.

In previous independent studies, 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.

'Strikingly, the plasma levels of glycine are decreased in all subjects with the above-mentioned diseases compared with healthy subjects,' says Professor Jens Nielsen at Chalmers. '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.'

'The discovery that the bacteria in our small intestine consume glycine and regulate glutathione metabolism may lead to the development of food products that can deliver beneficial bacteria (probiotics) to the gut. The results of the study may help us understand how bacteria play a role in the metabolic processes involved in the development of obesity, type 2 diabetes, non-alcoholic fatty liver disease and malnutrition,' he concluded.