More than 34 million Americans have diabetes and approximately 90–95% of them have type 2 diabetes (T2D). Globally, an estimated 462 million individuals are affected by T2D. The so-called “western diet,” high in saturated fats and refined sugars, is one of the primary factors. Now, Oregon State University (OSU) scientists have discovered that organisms in the gut microbiome play a key role in type 2 diabetes, and may lead to potential possible probiotic treatments.

Their findings were published in the journal Nature Communications in a paper titled, “Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet-induced diabetes.”

“Type 2 diabetes is, in fact, a global pandemic, and the number of diagnoses is expected to keep rising over the next decade,” said study co-leader Andrey Morgun, associate professor of pharmaceutical sciences in the OSU College of Pharmacy.

“Western diet (WD) is one of the major culprits of metabolic disease including type 2 diabetes with gut microbiota playing an important role in modulating effects of the diet,” the researchers wrote. “Herein, we use a data-driven approach (Transkingdom Network analysis) to model host-microbiome interactions under WD to infer which members of microbiota contribute to the altered host metabolism.”

In either case, sugar builds up in the bloodstream and if left untreated the effect is impairment to many major organs, sometimes to disabling or life-threatening degrees. A key risk factor for type 2 diabetes is being overweight, often a result of a western diet in combination with low physical activity.

There is growing evidence that dysbiosis of the gut microbiota is associated with the pathogenesis of both intestinal and extra-intestinal disorders.

“Some studies suggest dysbiosis is caused by complex changes resulting from interactions of hundreds of different microbes,” explained Natalia Shulzhenko, an associate professor of biomedical sciences in OSU’s Carlson College of Veterinary Medicine and the study’s other co-leader. “However, our study and other studies suggest that individual members of the microbial community, altered by diet, might have a significant impact on the host.”

The researchers used their new data-driven, systems-biology approach to study host-microbe interactions under a western diet. Their approach allowed them to observe whether individual members of the microbiota played a part in metabolic changes the diet induces in a host.

“The analysis pointed to specific microbes that potentially would affect the way a person metabolizes glucose and lipids,” Morgun noted. “Even more importantly, it allowed us to make inferences about whether those effects are harmful or beneficial to the host. And we found links between those microbes and obesity.”

The researchers identified four operational taxonomic units (OTUs) that appeared to affect glucose metabolism. The identified OTUs corresponded to four bacterial species: Lactobacillus johnsonii, Lactobacillus gasseri, Romboutsia ilealis, and Ruminococcus gnavus.

“The first two microbes are considered potential ‘improvers’ to glucose metabolism, the other two potential ‘worseners,'” Shulzhenko said. “The overall indication is that individual types of microbes and/or their interactions, and not community-level dysbiosis, are key players in type 2 diabetes.”

The researchers found that the Lactobacilli boosted mitochondrial health in the liver, and the mice receiving those Lactobacilli also had a lower fat mass index than those fed only a western diet.

“We found R. ilealis to be present in more than 80% of obese patients, suggesting the microbe could be a prevalent pathobiont in overweight people,” Shulzhenko said.

“Altogether, our observations support what we saw in the western diet-fed mice,” she said. “And in looking at all of the metabolites, we found a few that explain a big part of probiotic effects caused by Lactobacilli treatments.”

“Our study identifies potential probiotic strains for T2D and provides important insights into mechanisms of their action,” concluded the researchers.

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