Antibiotics and intergenerational transfer of microbiota: results from a non-clinical study

Vignette

If the microbiota of the mother is disturbed by antibiotics, that of the newborn could present the same imbalance, thus demonstrating a potential transfer from one generation to the next. The child could then be exposed to an increased risk of developing  inflammatory colitis.

 

Since antibiotics decrease the diversity of the intestinal microbiota, children have a higher risk of developing chronic inflammatory bowel disease (CIBD), especially colitis.  This impact has been vastly documented, but for the first time, an American team demonstrated in an animal model that antibiotic-induced changes in the maternal microbiota could generate CIBD in children through perinatal transfer.

Intergenerational transfer of microbiota...

To validate their initial assumption of intergenerational transfer, the researchers studied two mouse strains: wild mice and IL10−/− mice, a model deficient in interleukin 10 which spontaneously develops colitis in non-sterile conditions. Germ-free adult mice from both strains were either inoculated or not with intestinal microbiota shaped by penicillin exposure*. The first step was to compare, in germ-free conditions, the microbial communities found in the stools of mothers and their offspring, through 16S rRNA sequencing. The strong similarities between one generation and the other proves that an intergenerational transfer of intestinal microbiota occurs. Because this transfer was more marked in IL10−/− mice, the team expects this transfer to be dependent on the host’s genotype. By inoculating the mothers with altered microbiota instead of administering them antibiotics, the researchers demonstrated that the dysbiotic flora is responsible for the onset of the disease, and not the antibiotics per se.

...and vulnerability

The second step was to place the offspring in a standard environment and study its intestinal microbiota over time. Since it changed very little after a five-month period, the researchers concluded that the microbiota transfered by the mothers is persistent and that there is an increased risk of developing CIBD if the maternal microbiota is disrupted by antibiotics. Finally, thanks to the analysis of the bacterial communities observed during the study, the researchers were able to confirm the involvement of several bacterial genera which were suspected to play a role in the inflammatory process, especially Odoribacter, Bacteroides, Lachnospiraceae, Blautia and Rikenellaceae. On the contrary, Roseburia, Ruminococcus and Bilophila seem to have a protective role in the intestine. These new data should help assess the short- and long-term impacts of the use of antibiotics during pregnancy, on both mother and child.

*Using an inoculum ensured that the study results were not affected by antibiotic treatment.

Sources:

A. Schulfer, T. Battaglia, Y. Alvarez et al.: Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice. Nature Microbiology, June 2017.