
The brain appears to directly influence the gut microbiome, as brain signals altered the composition of gut microbes in mice in as little as 2 hours. The finding strengthens the notion that communication along the gut-brain axis goes both ways.
It is clear from previous studies that gut microbes can influence brain function and mood, but whether the opposite was true – that the brain could alter the gut microbiome – was less apparent.
at the August Pi i Sunyer Biomedical Research Institute in Spain and his colleagues used a technique called chemogenetics to activate specific neurons in the brains of 16 mice with specialised drugs. They targeted a subset of neurons in the hypothalamus known to regulate hunger. They then collected and analysed samples from four sections of the gut – 2 hours after neuron activation in half the mice and 4 hours later in the rest – and compared them with samples from a separate group of 16 mice that didn’t receive the drugs.
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The mice with activated neurons had an increase in the diversity of microbes in some regions of their guts, sort of like a microbial bloom. The effects were most pronounced in the duodenum – the first part of the small intestine – 2 hours after neuron activation. In this region, mice that underwent chemogenetics had microbiota that were, on average, five times more diverse than those of the control group.
The team then repeated the experiment in a separate group of mice, this time inhibiting the same neurons. This also led to significant changes in the gut microbiome, with some bacterial families declining more than 99 per cent, particularly in the middle part of the small intestine 2 hours after inhibition and in the final section of the intestine 4 hours later.
Further experiments in which the researchers injected hormones that regulate appetite into the brains of mice also revealed substantial changes to the gut microbiome in as little as 2 to 4 hours, with some bacterial families substantially increasing and others decreasing, depending on which portion of the gut samples came from.
These results suggest that the brain can rapidly modulate the composition of the gut microbiome. “We know that diet changes the gut microbiota composition – also drugs, environmental insults, et cetera,” says Claret. “But we never thought that the nervous system actually was able to modulate the composition of the gut microbiota.”
It isn’t clear why these changes occur, but Claret suspects it may be that when the brain detects hormones related to food intake, it relays signals to the gut, instructing microbes to ready themselves for digestion. While these findings haven’t been confirmed in people, brain circuits regulating appetite and digestion are quite similar between humans and rodents, he says.
If our brains can rapidly alter our gut microbes, this has significant implications for how we study the microbiome, says at Stanford University in California. First, it suggests that researchers should account for peoples’ mood and mental state when analysing microbiome samples. Second, we must start thinking of microbiota changes on an hourly scale, he says.
“The majority of people, even in the field, have the notion that changes in gut microbiota take a very long time to happen – over days or even weeks, but certainly not hours,” says Claret.
These findings also indicate there could be many more pathways linking the brain to the gut. “It could be that other brain regions, and neuronal types located in other areas that perform other functions, such as memory, may also have influences on gut microbial composition,” says Claret. “So I think that [these findings] open a new avenue of research in microbiology.”
Nature Metabolism