High-fat diets have influenced social behavior for generations

A study in mice showed that the mother's diet had an impact
not only on the health of her immediate offspring, but also on the offspring.
Compared with the control group, the offspring of mice fed high-fat food had altered gut microbiota and defects
in social interaction.
In turn, their offspring showed social dysfunction, as well as minor abnormalities
in the composition of the microbiome.
The findings were published Oct.
11 in
Cell Reports.

"The current study provides evidence for a growing body of evidence.
.
.
Kjersti Aagaard, a maternal-fetal medicine specialist at Baylor College of Medicine who was not involved in the study, wrote: "High-fat or Western-style feeding by mothers during pregnancy and lactation alters the microbiota
of their offspring in early and late childhood.
"

Notably, she adds, "this altered microbiota and associated abnormal neurobehaviors are evident not only in the first generation of offspring, but also in the second generation of offspring – even if only the 'grandmother' is fed a high-fat diet
.
" ”

High-fat diets have previously been shown to alter the gut microbiota
of mice and their immediate offspring.
In a 2016 study, some authors of the current paper showed that male pups born to mothers fed a high-fat diet experienced disturbances or dysregulated gut flora, with about a third
fewer bacterial species compared to the control group.
Shelly Buffington, a neuroscientist at the University of Texas Medical Division and co-author of the current study and the 2016 study, said male pups also showed reduced sociability and a lack of preference for social novelties — traits similar to one of the core phenotypes of
autism.

Buffington said: "I was thinking, we missed a little chance because we never followed the female
.
In mammals, there is this vertical transmission of the gut flora from mother to baby, so if (persistent microbial dysregulation) were in males, we would definitely see it
in females.
”

In fact, when the researchers in the current study analyzed the gut microbiota of female pups born to mice fed high-fat food before, during pregnancy, and within six weeks of lactation, they found similar effects to those found in male pups: About one-third of the bacterial species in the gut microbiota of the first generation of offspring, known as the F1 generation, disappeared
.

Caution should be exercised in interpreting these results, as they demonstrate that maternal microbiota is necessary and sufficient to
drive these adult phenotypes.

"Even if these F1 females now have a regular diet, if they have this poor gut microbiome, will that have an impact on the F2 generation?" Buffington asked recalled
.
To find out, the team fed F1 mice a normal diet and measured whether their offspring developed social impairments
.

Like F1 cubs, F2 pups themselves have never eaten high-fat foods
.
However, both male and female F2 pups showed deficiencies
in social behavior compared to pups whose grandmothers had a normal diet.
Female F2 mice showed statistically significant differences from control mice in only three behavioral tests designed to assess different aspects of
social functioning.
In contrast, F1 and F2 males showed serious deficiencies
in all three tests.

The researchers then tried feeding F2 mice a bacterium called Limosilactobacillus reuteri, which they had previously found to protect the offspring of females fed high-fat food from social deficits
.
Feeding Limosilactobacillus reuteri after weaning corrected the social behavior of
both sexes.
In male mice, social behavior reverted to the level
of mice with a regular grandmother's diet.

F2 females no longer showed defects
on a behavioral test that scored very low.
"In two other tests, it made female mice perform better and have stronger social behavior tendencies
than mice on a normal diet," Buffington said.
Buffington is an inventor whose patent relates to the use of Limosilactobacillus reuteri to treat social dysfunction
.

She added that the findings underscored the importance of
studying both sexes.
"We didn't anticipate [the effect on females] because a lot of the research on autism has been done almost always in male mice.
I think if we only focus on men, we're missing out on a lot of potentially exciting discoveries
.
Buffington says her lab is currently developing new ways to analyze the social behavior
of female mice.

The researchers found that despite the social impairment, the F2 pups had only minor disturbances in their microbiota: although the number of bacterial taxa in their guts was the same as in the guts of mice whose grandmothers had a normal diet, the species composition differed
.

Buffington speculates that the altered gut microbiota of the F1 generation, rather than the F2 generation, may be the culprit behind the "bad social behavior" of the young animals, adding that the F1 microbiota may have influenced their fetal neurodevelopment
.
The study showed that F3 mice born to these F2 female mice did not exhibit any social deficits
.

Aagaard writes that the findings "are consistent with the vertical transmission of microbes along the maternal line, leading to the transmission
of socially dysfunctional behaviors from generation to generation.
" ”

Aagaard says such problems can be addressed by stopping a high-fat diet around implantation or conception, with or without interventions to alter the microbiome, such as probiotics, and see if this eliminates the multigenerational effects
observed in this study.

As a next step, Buffington said, the team is investigating whether feeding probiotics to F1 females protects F2 pups from social deficits
.
As for the translatability of these findings for humans, Buffington notes: "We're just beginning to understand how this relatively recent change in [human] dietary patterns (for foods high in fat, sugar and processed foods) affects health and disease risk, not to mention its impact on generations
.
" As a result of this new study, the potential effects
of an unbalanced maternal diet on offspring.
”