TY - JOUR

T1 - Maternal prenatal gut microbiota composition predicts child behaviour

AU - Dawson, Samantha L.

AU - O'Hely, Martin

AU - Jacka, Felice N.

AU - Ponsonby, Anne-Louise

AU - Symeonides, Christos

AU - Loughman, Amy

AU - Collier, Fiona

AU - Moreno-Betancur, Margarita

AU - Sly, Peter

AU - Burgner, David

AU - Tang, Mimi L. K.

AU - Saffery, Richard

AU - Ranganathan, Sarath

AU - Conlon, Michael A.

AU - Harrison, Leonard C.

AU - Brix, Susanne

AU - Kristiansen, Karsten

AU - Vuillermin, Peter

AU - the BIS Investigator Group

N1 - Funding Information: Dr. O'Hely reports grants from National Health & Medical Research Council (Australia), during the conduct of the study; other from Prevatex Pty Ltd, outside the submitted work. Dr. Symeonides reports grants from NHMRC (Australian Government), grants from Shepherd Foundation (philanthropic foundation), during the conduct of the study. Dr. Loughman has a patent ‘Behavioural Treatment’ PCT/AU2019/050878 issued. Dr. Burgner reports grants from National Health and Medical Research Council (NHMRC) Australia, during the conduct of the study. Dr Jacka reports industry support for research from Meat and Livestock Australia, Woolworths Limited, the A2 Milk Company, and Be Fit Foods, and two relevant books for commercial publication. Dr. Tang reports personal fees from Prota Therapeutics, Abbott Nutrition Nestle health Science, Nestle Nutrition Institute, Nutricia and Bayer Pharmaceuticals, outside the submitted work; In addition, Dr. Tang has a patent ‘Methods and compositions for determining and for minimizing the likelihood of development of allergy in infants’ WO2018112553 pending to MCRI, and a patent ‘Behavioural Treatment’ WO2020037364 licensed to MCRI. All other authors have nothing to disclose. Funding Information: We would like to thank the study participants, as well as the entire BIS team which includes interviewers, nurses, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, and receptionists. We also thank the obstetric and midwifery teams at Barwon Health and Saint John of God Hospital Geelong for their assistance in recruitment and collection of biological specimens. We thank our collaborators from the Commonwealth Scientific and Industrial Research Organisation who conducted the SCFA measurements, and our collaborators at the J. Craig Venter Institute who conducted the 16S sequencing and preliminary bioinformatic analyses. We thank the National Health and Medical Research Council of Australia (1082307, 1147980), the Murdoch Children's Research Institute, Barwon Health and Deakin University for funding the Barwon Infant Study. Funding Information: We would like to thank the study participants, as well as the entire BIS team which includes interviewers, nurses, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, and receptionists. We also thank the obstetric and midwifery teams at Barwon Health and Saint John of God Hospital Geelong for their assistance in recruitment and collection of biological specimens. We thank our collaborators from the Commonwealth Scientific and Industrial Research Organisation who conducted the SCFA measurements, and our collaborators at the J. Craig Venter Institute who conducted the 16S sequencing and preliminary bioinformatic analyses. We thank the National Health and Medical Research Council of Australia (1082307, 1147980), the Murdoch Children's Research Institute, Barwon Health and Deakin University for funding the Barwon Infant Study. Publisher Copyright: © 2021

PY - 2021

Y1 - 2021

N2 - Background: Murine studies demonstrate that maternal prenatal gut microbiota influences brain development and behaviour of offspring. No human study has related maternal gut microbiota to behavioural outcomes during early life. This study aimed to evaluate relationships between the prenatal faecal microbiota, prenatal diet and childhood behaviour. Methods: A sub-cohort of 213 mothers and 215 children were selected from a longitudinal pre-birth cohort. Maternal prenatal exposure measures collected during the third trimester included the faecal microbiota (generated using 16S rRNA amplicon sequencing), and dietary intake. The behavioural outcome used the Childhood Behaviour Checklist at age two. Models were adjusted for prenatal diet, smoking, perceived stress, maternal age and sample batch. Findings: We found evidence that the alpha diversity of the maternal faecal microbiota during the third trimester of pregnancy predicts child internalising behaviour at two years of age (−2·74, (−4·71, −0·78), p = 0·01 (Wald test), R2=0·07). Taxa from butyrate-producing families, Lachnospiraceae and Ruminococcaceae, were more abundant in mothers of children with normative behaviour. A healthy prenatal diet indirectly related to decreased child internalising behaviours via higher alpha diversity of maternal faecal microbiota. Interpretation: These findings support animal studies showing that the composition of maternal prenatal gut microbiota is related to offspring brain development and behaviour. Our findings highlight the need to evaluate potential impacts of the prenatal gut microbiota on early life brain development. Funding: This study was funded by the National Health and Medical Research Council of Australia (1082307, 1147980), Murdoch Children's Research Institute, Barwon Health and Deakin University.

AB - Background: Murine studies demonstrate that maternal prenatal gut microbiota influences brain development and behaviour of offspring. No human study has related maternal gut microbiota to behavioural outcomes during early life. This study aimed to evaluate relationships between the prenatal faecal microbiota, prenatal diet and childhood behaviour. Methods: A sub-cohort of 213 mothers and 215 children were selected from a longitudinal pre-birth cohort. Maternal prenatal exposure measures collected during the third trimester included the faecal microbiota (generated using 16S rRNA amplicon sequencing), and dietary intake. The behavioural outcome used the Childhood Behaviour Checklist at age two. Models were adjusted for prenatal diet, smoking, perceived stress, maternal age and sample batch. Findings: We found evidence that the alpha diversity of the maternal faecal microbiota during the third trimester of pregnancy predicts child internalising behaviour at two years of age (−2·74, (−4·71, −0·78), p = 0·01 (Wald test), R2=0·07). Taxa from butyrate-producing families, Lachnospiraceae and Ruminococcaceae, were more abundant in mothers of children with normative behaviour. A healthy prenatal diet indirectly related to decreased child internalising behaviours via higher alpha diversity of maternal faecal microbiota. Interpretation: These findings support animal studies showing that the composition of maternal prenatal gut microbiota is related to offspring brain development and behaviour. Our findings highlight the need to evaluate potential impacts of the prenatal gut microbiota on early life brain development. Funding: This study was funded by the National Health and Medical Research Council of Australia (1082307, 1147980), Murdoch Children's Research Institute, Barwon Health and Deakin University.

KW - Behaviour

KW - Children

KW - Diet

KW - Gut-brain axis

KW - Microbiota

KW - Pregnancy

U2 - 10.1016/j.ebiom.2021.103400

DO - 10.1016/j.ebiom.2021.103400

M3 - Journal article

C2 - 34098340

AN - SCOPUS:85107793840

VL - 68

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

M1 - 103400

ER -