The Scientist reports on mice fed a high-fat diet, whose children and grandchildren still felt the effects in social behavior and overall health:
High-fat diets have previously been shown to alter the gut microbiome of mice, and of their immediate offspring. In a 2016 study, some of the authors of the current paper showed that male pups born to mothers fed a high-fat diet suffered disruptions, or dysbiosis, in their gut microbiota, with roughly a third fewer bacterial species compared with controls. The male pups also showed reduced sociability and a lack of preference for social novelty—traits similar to one of the core phenotypes of autism, says Shelly Buffington, a neuroscientist at the University of Texas Medical Branch and a coauthor of both the current study and the 2016 study.
“I got thinking that we had missed a little bit of an opportunity, because we never followed up on the females,” says Buffington. “In mammals, there’s this vertical transmission of gut microbiota from mom to baby, so if [the enduring dysbiosis] was in the males, surely we would see it in the females too.”
Indeed, when the researchers behind the current study analyzed the gut microbiome of female pups born to mice that had been fed a high-fat diet for six weeks prior to conception, during gestation, and during lactation, they found a similar effect to the one they had found in male pups: About a third of bacterial species had been lost from the gut microbiomes of the first, or F1, generation of offspring.
Like the F1 pups, the F2 offspring never received a high-fat diet themselves. Nevertheless, both male and female F2 pups showed deficits in social behavior compared to pups whose grandmothers had eaten normal diets. The female F2 mice only showed a statistically significant difference from control mice on one of three behavioral tests designed to assess different aspects of social function. In contrast, the F1 and F2 males showed strong deficits in all three tests.
The researchers then tried feeding the F2 mice a bacterium called Limosilactobacillus reuteri, which they had previously shown protected against social deficits in the offspring of mothers fed a high-fat diet. Feeding L. reuteri after weaning rectified social behavior in both sexes. In the males, social behaviors were rescued to the levels observed in mice whose grandmothers ate regular diets.
The F2 females no longer showed a deficit in the one behavioral test they’d scored poorly on. “In the other two tests, it caused the females to perform even better, have a stronger inclination towards social behavior than the regular diet counterparts,” says Buffington, who is named as an inventor on a patent related to the use of L. reuteri for treating disorders characterized by social dysfunction.
You can read more of Buffington’s team’s research here, in Cell Reports.