Influence of Early Life Factors, including breast milk Composition, on the Microbiome of Infants Born to Mothers with and without Inflammatory Bowel Disease

Author:

Sabino J123,Tarassishin L1,Eisele C14,Hawkins K1,Barré A1,Nair N15,Rendon A1,Debebe A1,Picker M1,Agrawal M26,Stone J7,George J2,Legnani Peter2,Maser Elana2,Chen Ching-Lynn7,Thjømøe Anne8,Mørk Einar8,Dubinsky M9,Hu J1,Colombel J F2,Peter I1,Torres J2101112

Affiliation:

1. Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences , New York, NY , USA

2. Icahn School of Medicine at Mount Sinai, Division of Gastroenterology, Department of Medicine , New York, NY , USA

3. Department of Gastroenterology, University Hospitals of Leuven , Leuven , Belgium

4. College of Medicine, Pennsylvania State University College of Medicine , Hershey, PA , USA

5. Department of Nutrition, Harvard T.H. Chan School of Public Health , Boston, Massachusetts

6. Center for Molecular Prediction of IBD [PREDICT], Department of Clinical Medicine, Aalborg University , Aalborg , Denmark

7. Gastroenterology Division, Icahn School of Medicine at Mount Sinai, Department of Obstetrics, Gynecology and Reproductive Sciences , New York , NY , USA

8. CALPRO AS , Lysaker , Norway

9. Icahn School of Medicine at Mount Sinai, Division of Pediatric Gastroenterology and Hepatology , New York , NY, USA

10. Gastroenterology Division, Hospital Beatriz Ângelo , Loures , Portugal

11. Gastroenterology Division, Hospital da Luz , Lisbon , Portugal

12. Faculdade de Medicina, Universidade de Lisboa , Portugal

Abstract

Abstract Background and Aims Herein we analysed the influence of early life factors, including breast milk composition, on the development of the intestinal microbiota of infants born to mothers with and without IBD. Methods The MECONIUM [Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome] study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analysed using 16s rRNA sequencing and faecal calprotectin. Breast milk proteomics was profiled using Olink inflammation panel. Results We analysed gut microbiota of 1034 faecal samples from 294 infants [80 born to mothers with and 214 to mothers without IBD]. Alpha diversity was driven by maternal IBD status and time point. The major influencers of the overall composition of the microbiota were mode of delivery, feeding, and maternal IBD status. Specific taxa were associated with these exposures, and maternal IBD was associated with a reduction in Bifidobacterium. In 312 breast milk samples [91 from mothers with IBD], mothers with IBD displayed lower abundance of proteins involved in immune regulation, such as thymic stromal lymphopoietin, interleukin-12 subunit beta, tumour necrosis factor-beta, and C-C motif chemokine 20, as compared with control mothers [adjusted p = 0.0016, 0.049, 0.049, and 0.049, respectively], with negative correlations with baby´s calprotectin, and microbiome at different time points. Conclusion Maternal IBD diagnosis influences microbiota in their offspring during early life. The proteomic profile of breast milk of women with IBD differs from that of women without IBD, with distinct time-dependent associations with baby’s gut microbiome and feacal calprotectin.

Funder

International Organization for the Study of Inflammatory Bowel Diseases

Crohn's and Colitis Foundation

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Gastroenterology,General Medicine

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