Dataset Information

Paternal microbiome perturbations impact offspring fitness

ABSTRACT:

The gut microbiota operates at the interface of host-environment interactions to influence human homeostasis and metabolic networks. Environmental factors that unbalance gut microbial ecosystems can therefore elicit physiological and disease-associated responses across somatic tissues. However, the systemic impact of the gut microbiome on the germline - and consequently on the F1 offspring it gives rise to - is unexplored. Here we show that the gut microbiota act as a key interface between paternal preconception environment and intergenerational health in mice. Perturbations to the gut microbiota of prospective fathers increase the probability of their offspring presenting with low birth weight, severe growth restriction and premature mortality. Transmission of disease risk occurs via the germline and is provoked by pervasive gut microbiome perturbations, including non-absorbable antibiotics or osmotic laxatives, but is rescued by restoring the paternal microbiota before conception. This effect is linked with a dynamic response to induced dysbiosis in the male reproductive system, including impaired leptin signalling, altered testicular metabolite profiles and remapped small RNA payloads in sperm. As a result, dysbiotic fathers trigger an elevated risk of in utero placental insufficiency, revealing a placental origin of mammalian intergenerational effects. Our study defines a regulatory ‘gut-germline axis’ in males, which is sensitive to environmental exposures and programs offspring fitness through impacting placental function.

INSTRUMENT(S): Liquid Chromatography MS -, Liquid Chromatography MS - negative - reverse phase

SUBMITTER: Saravanan Devendran

PROVIDER: MTBLS1629 | MetaboLights | 2024-02-12

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS1629	Other
	FILES	Other
	a_MTBLS1629_LC-MS_negative_metabolite_profiling.txt	Txt
	a_MTBLS1629_LC-MS_positive_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt

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Publications

Paternal microbiome perturbations impact offspring fitness.

Argaw-Denboba Ayele A Schmidt Thomas S B TSB Di Giacomo Monica M Ranjan Bobby B Devendran Saravanan S Mastrorilli Eleonora E Lloyd Catrin T CT Pugliese Danilo D Paribeni Violetta V Dabin Juliette J Pisaniello Alessandra A Espinola Sergio S Crevenna Alvaro A Ghosh Subhanita S Humphreys Neil N Boruc Olga O Sarkies Peter P Zimmermann Michael M Bork Peer P Hackett Jamie A JA

Nature 20240501 8012

The gut microbiota operates at the interface of host-environment interactions to influence human homoeostasis and metabolic networks1-4. Environmental factors that unbalance gut microbial ecosystems can therefore shape physiological and disease-associated responses across somatic tissues5-9. However, the systemic impact of the gut microbiome on the germline-and consequently on the F1 offspring it gives rise to-is unexplored10. Here we show that the gut ...[more]

PMID: 38693261

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