Discover the links between diet, gut health and immunity

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High protein diet model in the induction of the sIgA response. A diet rich in protein promotes the production of succinate by the intestinal microbiota. Elevated levels of luminal succinate induce intestinal bacterial cell stress and the production of reactive oxygen species (ROS), which promote vesiculation and increased production of microbiota-derived extracellular vesicles. Microbiota-derived extracellular vesicles can directly activate TLR4 expressed on the intestinal epithelium, activating downstream NFκB signaling that results in increased expression of APRIL, CCL28, and PIGR, which drives the T cell-independent sIgA response. TLR4 signaling also potentiates pro-inflammatory responses, leading to more severe DSS-induced colitis. The increase in intestinal succinate observed in patients with IBD may contribute to the pathology of the disease by promoting the production of microbiota-derived extracellular vesicles and the TLR4/NFκB signaling pathway. Credit: Nature Communication (2022). DOI: 10.1038/s41467-022-31761-y

A preclinical study from the University of Sydney found that a high-protein diet can alter the gut microbiota, triggering an immune response. The researchers say the study brings us closer to understanding the impact of diet on gut health and immunity.

“Our work focuses on how the gut microbiota – the trillions of bacteria that inhabit the gut – affect the immune system,” said Associate Professor Laurence Macia of the Charles Perkins Center and the Faculty of Medicine and Health at the University.

“Our ultimate goal is to understand how we can manipulate bacteria to optimize health, and we know that one of the easiest ways to modify the microbiota is to modify the diet.”

Traditionally, however, scientists have focused on the role of dietary fiber in maintaining a healthy gut.

In this unpublished study, published in Nature Communicationthe Charles Perkins Center team used sophisticated modeling to explore the impact of 10 diets with different composition of macronutrients – proteins, fats and carbohydrates in mice.

They discovered that a high protein diet modified the composition and activity of the intestinal microbiota.

Mice fed high protein diet increased their production of bacterial extracellular vesicles, a complex cargo containing bacterial information such as DNA and proteins. The agency then viewed this activity as a threat and triggered a sequence of events where immune cells traveled through the intestinal wall.

“Here we discovered that protein had a huge impact on the gut microbiota and it was not so much the type of bacteria present as the type of activity. Essentially, we discovered a new communication pathway between gut bacteria and the host that was protein-mediated,” said Associate Professor Macia.

Although it’s too early to tell if this research could translate to humans, the researchers say that the activation of the immune system can turn out to be good news or bad news.

“By increasing the antibodies in the gut, you can see strong protection against potential pathogens, for example salmonella, but on the downside, an activated immune system could mean you are at increased risk of colitis, a inflammatory bowel diseaseor autoimmune diseases like Crohn’s disease,” said lead author and post-doctoral researcher Jian Tan.

The findings appear consistent with the population impacts of modern diets, with the Western world experiencing lower rates of gastrointestinal infections but higher rates of chronic disease.

This advance in knowledge was made possible by the fusion of academic disciplines for which the Charles Perkins Center has become well known.

The study used the Geometric Framework for Nutrition developed by Professor Stephen Simpson and Professor David Raubenheimer, stemming from the study of ecology.

“The ‘Nutritional Geometry’ framework allows us to plot foods, meals, diets and diets together according to their nutrient composition, helping researchers observe otherwise overlooked patterns in the links between certain diets, health and disease,” Professor Simpson said. , Academic Director of the Charles Perkins Center.

“This is the first time this model has been applied in immunology and it could only have happened here at the Charles Perkins Center. We are excited about what could happen next,” said Associate Professor Macia.


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More information:
Jian Tan et al, Dietary proteins increase T-cell independent sIgA production by altering gut microbiota-derived extracellular vesicles, Nature Communication (2022). DOI: 10.1038/s41467-022-31761-y

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