The Brain Speaketh Unto the Gut and the Gut Answereth Back

In the previous News Blog I mentioned the hypothesis that an altered gut microbiome may trigger chronic fatigue syndrome.[1] I promised more on the topic. Many years ago I chaired the Scientific Advisory Committee for the MRC Oracle study. This was a study of antibiotics versus no antibiotics to prevent preterm labour.[2] There were no differences in short-term outcomes in children of the antibiotic versus control mothers. But CLAHRC WM associate Sara Kenyon and her colleagues followed the children up to the age of seven. The results show markedly higher levels of cerebral palsy in the intervention (antibiotic) group over the control (no antibiotics) group, and in one of the two antibiotics used the risk of other functional impairments was also increased.[3] I was also inclined to pass this off as a chance finding – type 1 error. Now I am not so sure – recent evidence in Nature [4] shows that antibiotics in baby mice cause changes on their frontal cortices, affect the blood-brain barrier, and alter behaviour. These changes are partially preventable by probiotic administration. If maternal antibiotics are bad for the baby brain, then presumably so is neonatal antibiotic administration. It would be interesting to follow up neonates of given gestational age, mass and clinical condition to compare outcomes in those given antibiotics and non-antibiotics. Yes, I know it will be confounded by indication for antibiotics, so a null result would be more informative than a positive result.

— Richard Lilford, CLAHRC WM Director


  1. Lilford RJ. Biological Underpinnings of Chronic Fatigue? NIHR CLAHRC West Midlands News Blog. 21 April 2017.
  2. Kenyon S, Taylor DJ, Tarnow-Mordi W, for the ORACLE Collaborative Group. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. Lancet. 2001; 357: 979-88.
  3. Kenyon S, Pike K, Jones DR, Brocklehurst P, Marlow N, Salt A, Taylor DJ. Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial. Lancet. 2008; 372: 1319-27.
  4. Leclercq S, Mian FM, Stanisz AM, et al. Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior. Nat Commun. 2017; 8: 15062.

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