Both cause and cure for diabetes could be in your gut
- 16:16 06 February 2015 by Andy Coghlan
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Having the wrong kind of gut bugs might help cause type-1 diabetes. But a genetically engineered form of a microbe found in some dairy products could trick intestine cells into making much-needed insulin.
The discovery that "the wrong bacteria" can make type-1 diabetes more likely comes from a 3-year analysis of 33 Finnish infants genetically identified to be at a higher risk of diabetes.
By age 3, four of those children had developed diabetes, in which the body cannot regulate blood glucose because it can't make the hormone insulin. Ramnik Xavier. of Massachusetts General Hospital in Boston, and his team found that they had a narrower range of bugs in their guts than the other children: typically around 25 per cent fewer species than the unaffected infants. The four children also had more of the types of species that are known to trigger gut inflammation, a possible prelude to type-1 diabetes, in which the body's immune system mistakenly produces antibodies that attack and destroy the beta cells of the pancreas that normally make insulin.
But although only four developed diabetes during the study, 11 had started to make autoantibodies, the researchers found.
"It might mean that even if the autoantibodies are starting to be made, you need a second insult or signal to tip patients over into type-1 diabetes, and the change in the microbiome might be the culprit," says Xavier.
This means that keeping the microbiome stable might be a way to prevent the disease. "If you know what the key
bugs make, you may be able to look at giving cocktails of bugs or their metabolites to keep the disease at bay," says Xavier.
Mimicking the pancreas
One potential treatment could be engineered bugs developed by a separate team in New York. John March of Cornell University in Ithaca, New York and his team took the bacterium Lactobacillus gasseri. which is found in some probiotic yogurts, and equipped it with a human gene for a hormone called glucagon-like peptide-1. In the intestines of diabetic rats, they found that GLP-1 triggered some gut cells to become more like those that manufacture insulin in the pancreas.
The insulin these cells produced acted on blood sugar levels in the same way as insulin from the pancreas. "It moves the centre of glucose control from the pancreas to the gut," says March.
After receiving the bacteria daily for three months, glucose levels in the rats fell by 30 per cent, compared with controls. After meals, these rats could reduce their blood glucose levels as quickly as rats with a healthy pancreas, while the bacteria had no impact on blood glucose when given to healthy rats - suggesting that the bacteria prompt gut insulin production only if the host's pancreas is not working properly.
March is optimistic that the lactobacilli will also work in humans because, when he exposed lab cultures of healthy human gut cells to the bacteria, they turned into insulin-making cells too.
The aim is to develop a pill containing the bacteria that people with type-1 and type-2 diabetes could take daily. March says it could be available within two years.
Journal reference: Cell Host & Microbe. DOI: 10.1016/j.chom.2015.01.001; and Diabetes. DOI: 10.2337/db14-0635/-DC1