Inheritance through the microbiome

Behavioral traits are usually only attributed to genes or upbringing. A new experimental study now shows that the composition of the intestinal flora alone can also shape and pass on behavior over several generations, without any genetic changes.

Microorganisms of the gut microbiome can influence numerous host functions, including behavior. It has long been assumed that differences in the microbiome produce different phenotypes of a host and can thus also shape evolution. It was previously unclear whether behavioral traits can actually be inherited over generations (!).

What was done in the study?

First, two wild-derived mouse lines were compared, which differed significantly in their running activity: One mouse was very active, while the other was significantly lazier. Fecal transfers between the mice showed that the difference in behavior was mediated by the gut microbiome: Recipients with the microbiome of the more active strain covered significantly more distance than those with the gut flora of the more inactive strain.
The researchers then conducted a selection experiment. In four consecutive rounds, the microbiome of the most inactive mouse was always transferred to germ-free recipients in order to gradually read out a lower level of activity. In parallel, a control line received randomly selected donors in each generation. In fact, the walking distance in the selection line decreased significantly over the generations, while the control line maintained its initial level. This proves that a sustainable change in behavior can be induced simply by passing on the intestinal flora.

What has been observed in the microbiome?

A significant increase in lactobacilli (genera Lactobacillus and Limosilactobacillus) and a decrease in other bacteria were associated with the lower activity.
In addition, the bacterial tryptophan degradation product indole-3-lactic acid (ILA) increased in the “lazy” microbiota. ILA was positively correlated with the proportion of Lactobacillus in the gut – confirming their role as ILA producers.

What does that mean? Why was it important?

Biologically, the work provides clear evidence that symbiotic gut bacteria can act as a non-genetic inheritance factor for behavioral traits.
The gut flora thus extends the phenotypic scope of a host beyond its own genome. Certain microbiome components can be selected for a behavior independently of the host genotype and pass it on stably over generations.
Lactobacilli and their tryptophan metabolite ILA in particular prove to be mediators at the gut-brain interface.

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How was the causal link tested?

An isolated Lactobacillus johnsonii strain was fed orally to mice. This significantly reduced their running activity compared to control animals. The treated mice ran less and slower, with unchanged eating behavior and body weight.
Similarly, the direct infusion of ILA into the intestine led to reduced activity, with no effect on food consumption or weight.
This proved that the reduced activity is directly caused by the metabolite ILA produced by lactobacilli.

In other words:

Behavioral traits can be passed on independently of the genome simply by passing on the gut microbiome.
Behavior can be inherited. Not via genes, but via the microbiome!

But how can a microbiome be inherited?

For example, through birth or nursing behavior: In humans and mice, initial colonization occurs via birth, licking/kissing of newborns, breast milk and later – especially in mice – through coprophagy (ingestion of faecal particles).
Studies show that certain bacteria are passed on stably over many generations. If a microorganism gives its host an advantage, it can be passed on together with this host type and thus become part of natural selection.

What impact could this have one day?

In the long term, this finding opens up new possibilities for promoting specific desired properties through microbiome manipulation:

Animal husbandry

Behavioral and performance traits could be specifically optimized by focusing on advantageous microbiota instead of genetic selection.

Medicine

Certain probiotic bacteria or their metabolites (such as ILA) could one day be used to influence behavioral or neurological disorders.

What do we learn from this?

The concept helps to understand how animals can adapt to new environmental conditions without DNA mutation:
In a changing climate or habitat, the flexible co-inheritance of microbes could promote short-term advantageous behavioral adaptations.

Source:

Suzuki TA, Tanja A-S, Waters JL, Jakob D, Vu DL, Ballinger MA, Rienzi SCD, Chang H, Araujo IE de, Tyakht AV, Ley RE. 2025. Selection and transmission of the gut microbiome alone can shift mammalian behavior. Nat Commun 16:9482. Link to the paper.