The risk of developing type I diabetes may be lowered through the transfer of gut bacteria from a less susceptible donor, a new study shows.
By feeding diabetes-susceptible mice with water laced with bacteria obtained from the gut of diabetes-resistant mice, researchers stably altered the composition of the gut bacteria community in the recipients to resemble that of the donors. This reduced damage to insulin-secreting cells and delayed the onset of diabetes.
“These [gut] bacteria play important roles in disease development, yet their role has been neglected for many years,” said Li Wen, the director of the core laboratory of the Yale Center for Clinical Investigation and senior author of the study. Wen pointed to a 2008 paper published in Nature where she and other researchers reported that gut bacteria influences the development of type I diabetes.
Susan Wong, Cardiff University professor of Experimental Diabetes & Metabolism and another author of the study, explained that these bacteria interact with cells of the gut wall and associated immune cells, stimulating the production of protective antibodies and immune signaling molecules.
The sharp increase in the incidence of type I diabetes in Western countries over the past four decades may be explained, paradoxically, by improvements in hygiene, Wen said. According to a theory known as the hygiene hypothesis, the immune system fails to develop properly due to reduction of exposure to bacteria in the environment. Immune cells wrongly attack insulin-secreting cells in the body, reducing insulin secretion and raising the blood sugar level, resulting in type I diabetes.
According to Wen, studying gut bacteria is challenging because many cannot be cultured in the lab and researchers do not know their identities. She said the rise of genomic sequencing has facilitated this work by allowing researchers to identify many previously unknown gut bacteria.
Following up on their 2008 paper, Wen and Wong said they wanted to investigate how the composition of gut bacteria could be altered, and if this could confer protection against diabetes.
“We found that the younger the mice you give good bacteria or bad bacteria, the stronger the effect down the road,” said Wen.
This bacteria transfer has a long-term effect, said Jian Peng, research associate at the Yale School of Medicine and first author of the study. She added that when the team transferred the bacteria to one-month-old mice, the protective effect could still be observed after eight months — roughly 50 years in human years.
Wong said scientists do not yet know how large a contribution gut bacteria make to predisposition to type I diabetes, given that this is just one of a number of genetic and environmental factors. Still, Wen is hopeful that the transfer of gut bacteria will serve as an additional approach to treat the disease. Gut bacteria transfer is already a federally approved treatment for inflammatory bowel disease, another immune-related condition, she said.
This work also suggests that scientists may be able to develop bacterial biomarkers for type I diabetes in the future, said Sukanya Narasimhan, research scientist at the Yale School of Medicine and another author of the study.
Moving forward, researchers will need to identify the exact combinations of gut bacteria that are most beneficial and the precise mechanisms through which they exact a protective effect, Wong said.
Other groups have been studying the effect of gut bacteria on immune-related diseases such as rheumatoid arthritis, lupus and multiple sclerosis, but Wen said that different bacteria will likely be beneficial to different diseases.
“There is no magic bullet to target every single disease,” she said.
The team consisted of researchers from Yale, Cardiff University, Imperial College London and the University of Nebraska.