Diet has a bigger say on gut microbes than the intestinal defense molecules

Researchers at Umeå University, Sweden, have found that among the many factors that shape the intestinal microbiota composition, diet has a much stronger impact than defensins, which are intestinal defence molecules produced by the body. Instead, they identified a possible role for these molecules in preventing increased blood glucose levels after consumption of high-caloric “Western-style diet”.

“While the effect of defensins in shaping the adult microbiota composition is rather minor when compared to diet, defensins still have a very important role in protecting us against microbial infections; and our research highlights their protective role against the metabolic complications that can arise after the intake of a high-fat and high-sugar Western-style diet,”says Fabiola Puértolas Balint, PhD student at the Department of molecular biology at Umeå University.

She is working  in Björn Schröder’s research group, which is also affiliated to Umeå Centre of Microbial Research, UCMR, and The Laboratory for Molecular Infection Medicine Sweden, MIMS, at Umeå University.

The gut microbiota refers to the community of trillions of microorganisms that live inside everyone’s gut. Over the past decades, the abundance of specific bacteria in this community has been extensively studied due to its connection to many diseases, including inflammatory bowel diseases, obesity and diabetes, and even psychological disorders. The microbial community is seeded during birth, after which several internal and external factors help shaping the community to its final composition. These factors include, among others, diet (especially fibre), genetics, medication, exercise, and defence molecules, the so-called antimicrobial peptides.

Antimicrobial peptides can be regarded as the body´s own naturally produced antibiotic molecules. In particular, the largest group of antimicrobial peptides – the defensins – is produced by all body surfaces, including the skin, the lungs and the gastrointestinal tract. Defensins are considered the immune system´s first line of defence against infections but at the same time they have also been thought to be essential in shaping the microbiota composition in the small intestine. However, it was so far unclear how big their effect was as compared to diet, which is known to have a major impact.

To investigate this, the researchers from Björn Schröder lab used normal healthy mice and compared their microbiota composition in the small intestine to mice that could not produce functional defensins in the gut, and then both mouse groups were fed either a healthy diet or a low-fibre Western-style diet.

“When we analysed the microbiota composition inside the gut and at the gut wall of two different regions in the small intestine, we were surprised – and slightly disappointed – that defensins had only a very minor effect on shaping the overall microbiota composition,” says Björn Schröder.

However, the intestinal defensins still had some effect directly at the gut wall, where the defensins are produced and secreted. Here, a few distinct bacteria seemed to be affected by the presence of defensins, among them Dubosiella and Bifidobacteria, likely due to selective antimicrobial activity of the defensins.

“To our surprise, we also found that the combination of eating a Western-style diet and lacking functional defensins led to increased fasting blood glucose values, which indicated that defensins may help to protect against metabolic disorders when eating an unhealthy diet,” says Björn Schröder.

The results suggest that strategies that aim to positively modulate the microbiota composition should rather focus on diet, as modulation of the composition via increased production of own host defense molecules, such as defensins, may have only a small impact on the overall composition. However, it is possible that especially early in life, when the microbiota community is not fully matured yet, defensins may have a stronger effect on the microbial composition. Still, increasing the production of defensins may be a valuable option to prevent the development of metabolic disorders.