On the cutting edge of digestive health

by Keith Nunes
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Growing evidence suggests changes in the microbiome composition may contribute to development of diseases ranging from cancer to chronic inflammatory disorders such as multiple sclerosis.

KANSAS CITY — A report published this past November by the market research firm Packaged Facts highlighted the key trends and developments taking place in the market for functional foods and ingredients. Most notably, the report highlighted five categories of functional food ingredients manufacturers should pay attention to in 2015, including protein, omega-3 fatty acids, vitamin D, magnesium and microalgae. Conspicuously missing from the list were ingredients associated with digestive health.

That may change in the coming years as more research not only further identifies the benefits of digestive health, but also how those benefits are derived. The latter point has been a blind spot, but now several study results indicate researchers are on the cusp of identifying the mechanisms that associate digestive health with overall health outcomes.

While much of the research has been done with mice, it is clear the results may translate to humans. For example, diet-induced changes in gut bacteria may alter susceptibility to an auto-inflammatory bone disease by modifying the immune response, according to a study conducted by researchers at St. Jude Children’s Research Hospital in Memphis, Tenn. The findings appeared on-line in the journal Nature.

The research provides insight into how the bacteria and other microorganisms that live in the intestines affect health. The microbes make up the intestinal microbiome, an ecosystem in the body that aids digestion and helps to “educate” the immune cells that guard against infection.

Growing evidence suggests changes in the microbiome composition may contribute to development of diseases ranging from cancer to chronic inflammatory disorders such as multiple sclerosis, according to the researchers. The mechanisms involved, however, are poorly understood.

“These results are exciting because they help to explain how environmental factors like diet can influence susceptibility to auto-inflammatory diseases,” said the study’s lead author Thirumala-Devi Kanneganti, Ph.D., a member of the St. Jude Department of Immunology. “While multiple lines of evidence have suggested that diet can impact human disease, the scientific mechanism involved was a mystery. Our results demonstrate that diet can influence immune-mediated disorders by shaping the composition of the gut microbiome, which our findings suggest play a role in immune regulation.”

The study was done in a mouse model of the inflammatory childhood bone disorder called chronic recurrent multifocal osteomyelitis, which leads to lesions, inflammation and pain in the bones of children. The mice involved in the study carry a mutation in a gene identified as Pstpip2 that leads to osteomyelitis early in life.

The researchers showed that changing the nutritional composition of the animals’ diets led to marked increases and decreases of certain intestinal bacteria. Affected bacteria included Prevotella, which have been implicated in causing osteomyelitis, arthritis, periodontal disease and other inflammatory disorders in humans.

A diet that limited intestinal Prevotella growth protected the mutant mice from developing osteomyelitis. The same diet was associated with reduced production of the immune molecule interleukin-1 beta that promotes inflammation. Earlier work from Dr. Kanneganti’s laboratory demonstrated interleukin-1 beta fueled osteomyelitis in the mutant mice. In this study, researchers reported that dietary changes impacted the supply of the interleukin molecule in immune cells.

To confirm the connection between the intestinal microbiome and osteomyelitis, researchers treated mice that were fed the disease-promoting diet with a cocktail of broad-spectrum antibiotics. Treatment was followed by a reduction in Prevotella as well as intestinal levels of interleukin-1 beta. In addition, fewer mice developed osteomyelitis.

In a series of probiotic experiments, the researchers showed that transplanting the intestinal microbiome from healthy mice protected the at-risk, mutant mice from osteomyelitis.

“The results suggest probiotics might provide a more targeted method for suppressing production of IL-1 beta (interleukin-1) and protecting against auto-inflammatory diseases,” said John Lukens, Ph.D., a St. Jude postdoctoral fellow, another author of the study.

The immune system

Past research has shown that good digestive health will benefit the immune system. But new research shows there may be a relationship between the immune system and gut health. A University of Utah study published Jan. 22 in the journal Cell Host and Microbe shows that mice deficient for a component of the immune system, a protein called MyD88, have an imbalanced gut bacterial community and are more susceptible to contracting a severe inflammatory bowel disease-like illness.

The results show that the immune system encourages growth of a healthy community of “good” bacteria that is important for digestive health, according to the researchers. This perspective on immune system function is in contrast to its best known role as the first line of defense in the fight against pathogens, including invasive bacteria.

“Our work highlights that the immune system shapes the composition of bacterial communities in the intestine,” said senior author June Round, Ph.D., assistant professor of pathology at the University of Utah School of Medicine. “This interaction is important because it’s becoming more and more clear that resident microbes are very important for our health.”

Loss of MyD88 disturbs the microbial community because it disrupts production of IgA, an antibody that acts like a gatekeeper that controls which types of bacteria, and how many, are allowed to inhabit the gut. By performing inventories of total gut bacteria compared to species that bind IgA, the scientists determined that without MyD88, IgA failed to recognize species that it can otherwise.

The work not only demonstrated that a balanced microbial community promotes digestive health, but that it also shapes the host’s immune system. Mice raised in a sterile, germ-free environment have a faulty immune system, a defect that may be fixed if they are fed bacterial components that activates the immune system.

“There is a conversation between our immune system and our resident bacteria,” Dr. Round said. “The microbes can send signals that tell our immune system how to develop and in turn our immune system can shape what types of microbes live on our body.”

As researchers learn more about the beneficial types of microbes consumers need to reside in their gut, the more targeted ingredient suppliers may be in their development of functional ingredients that optimize gut health and, in turn, may improve overall consumer health.

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