Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity

Donald D Nyangahu; Katie S Lennard; Bryan P Brown; Matthew G Darby; Jerome M Wendoh; Enock Havyarimana; Peter Smith; James Butcher; Alain Stintzi; Nicola Mulder; William Horsnell; Heather B Jaspan

doi:10.1186/s40168-018-0511-7

Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity

Donald D Nyangahu, Katie S Lennard, Bryan P Brown, Matthew G Darby, Jerome M Wendoh, Enock Havyarimana, Peter Smith, James Butcher, Alain Stintzi, Nicola Mulder, William Horsnell, Heather B Jaspan

Microbes, Infections and Microbiomes

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Abstract

BACKGROUND: Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery.

RESULTS: In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4⁺ T cells and B cells, most notable Follicular B cells.

CONCLUSION: Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.

Original language	English
Article number	124
Number of pages	10
Journal	Microbiome
Volume	6
Issue number	1
Early online date	7 Jul 2018
DOIs	https://doi.org/10.1186/s40168-018-0511-7
Publication status	Published - Dec 2018

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10.1186/s40168-018-0511-7Licence: Creative Commons: Attribution (CC BY)

Nyangahu_et_al_Disruption_of_maternal_gut_microbiota_during_gestation_alters_offspring_microbiota_and_immunity_Microbiome_2018
Donald D. Nyangahu, Katie S. Lennard, Bryan P. Brown, Matthew G. Darby, Jerome M. Wendoh, Enock Havyarimana, Peter Smith, James Butcher, Alain Stintzi, Nicola Mulder, William Horsnell and Heather B. Jaspan, Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity, Microbiome, 2018, 6:124; https://doi.org/10.1186/s40168-018-0511-7.
Final published version, 1.37 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

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title = "Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity",

abstract = "BACKGROUND: Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery.RESULTS: In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells.CONCLUSION: Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.",

author = "Nyangahu, {Donald D} and Lennard, {Katie S} and Brown, {Bryan P} and Darby, {Matthew G} and Wendoh, {Jerome M} and Enock Havyarimana and Peter Smith and James Butcher and Alain Stintzi and Nicola Mulder and William Horsnell and Jaspan, {Heather B}",

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AU - Nyangahu, Donald D

AU - Lennard, Katie S

AU - Brown, Bryan P

AU - Darby, Matthew G

AU - Wendoh, Jerome M

AU - Havyarimana, Enock

AU - Smith, Peter

AU - Butcher, James

AU - Stintzi, Alain

AU - Mulder, Nicola

AU - Horsnell, William

AU - Jaspan, Heather B

PY - 2018/12

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N2 - BACKGROUND: Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery.RESULTS: In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells.CONCLUSION: Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.

AB - BACKGROUND: Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery.RESULTS: In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells.CONCLUSION: Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.

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DO - 10.1186/s40168-018-0511-7

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JO - Microbiome

JF - Microbiome

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ER -

Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity

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