Restoring Microbiome of Babies Treated with Antibiotics Could Reduce Type 1 Diabetes Risk

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Results from a mouse study led by Rutgers University suggest that transferring maternal gut microbes to babies susceptible to type 1 diabetes who have had their gut microbiome wiped out by treatment with antibiotics could reduce their risk of developing the autoimmune disease.

Although this work is early stage, the researchers believe it may have relevance for human babies at risk of this type of diabetes. Other studies have shown that significant changes to the gut microbiome can be seen before and at the onset of type 1 diabetes in humans, suggesting a possible causal link, but the exact mechanism of this is not yet clear.

The gut microbiome at birth is minimal and develops over time, taking around three years to become as diverse as that of an adult. Babies initially gain most of their gut microbes from their mother both during birth and through breast feeding, as well as skin to skin touch. Early exposure to infections can lead to babies being treated with antibiotics and this can have a serious impact on their developing gut microbiome.

Martin Blaser, director of the Center for Advanced Biotechnology and Medicine at Rutgers, and colleagues study a mouse model of type 1 diabetes called the non-obese diabetic (NOD) mouse. In a similar way to humans, the mice have a predisposition to diabetes and a significant number (although not all) develop diabetes after a few months of age.

In previous work, Blaser and team found that early treatment with antibiotics led to gut microbiome disruption in the infant mice. The mice given antibiotics also seemed to develop diabetes more quickly at an earlier age. Blaser says this exposure to antibiotics “may change age-associated immunity and organ-specific inflammation, increasing risk of immune-mediated diseases.”

In this study, which is published in Cell Host & Microbe, the researchers found that transferring the maternal gut microbiota to young mice that had a disrupted gut microbiome from antibiotics seem to have a beneficial effect. It largely restored the gut microbiome and also stopped or slowed progression to diabetes by normalizing metabolic pathways.

Notably, they found that pups given maternal microbiota sampled on the day of their birth had the best outcomes. “This is consistent with the evidence that at birth, mothers pass a comprehensive microbiota to their offspring, with subsequent selection and succession of dominant species,” write the authors.

Further investigation suggested that there is a type 1 diabetes protection mechanism strongly linked to an immune peptide called Reg3g and also involving immune regulators CD44 and TLR2. In the mice treated with antibiotics, Reg3g was decreased possibly explaining the earlier onset type 1 diabetes in these animals.

“The mice that were exposed to antibiotics had the expression of indicator genes in their intestinal wall that were either too high or too low, but the transplant brought that back almost to the original levels and restored metabolic pathways,” said co-author Xue-Song Zhang, an assistant research professor at the Center for Advanced Biotechnology and Medicine at Rutgers. “We were able to identify groups of genes that returned to normal after the transplant as if the mice had never received the antibiotics.”

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