Depletion of the paternal gut microbiome alters sperm small RNAs and impacts offspring physiology and behavior in mice

Study information

Reviewed Marked as Reviewed by Svetlana up on 2024-10-25

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

39293692

DOI Digital object identifier for electronic documents.

https://doi.org/10.1016/j.bbi.2024.09.020

URI

https://pubmed.ncbi.nlm.nih.gov/39293692/

Authors

Masson BA, Kiridena P, Lu D, Kleeman EA, Reisinger SN, Qin W, Davies WJ, Muralitharan RR, Jama HA, Antonacci S, Marques FZ, Gubert C, Hannan AJ

Journal

Brain, behavior, and immunity

Year

2024

Keywords:

Antibiotics, Anxiety, Behavior, Depression, Dysbiosis, Gut microbiota, Microbiome, Noncoding RNAs, Paternal epigenetic inheritance

The paternal environment prior to conception has been demonstrated to influence offspring physiology and behavior, with the sperm epigenome (including noncoding RNAs) proposed as a potential facilitator of non-genetic inheritance. Whilst the maternal gut microbiome has been established as an important influence on offspring development, the impact of the paternal gut microbiome on offspring development, health and behavior is largely unknown. Gut microbiota have major influences on immunity, and thus we hypothesized that they may be relevant to paternal immune activation (PIA) modulating epigenetic inheritance in mice. Therefore, male C57BL/6J mice (F0) were orally administered non-absorbable antibiotics via drinking water in order to substantially deplete their gut microbiome. Four weeks after administration of the antibiotics (gut microbiome depletion), F0 male mice were then mated with naïve female mice. The F1 offspring of the microbiome-depleted males had reduced body weight as well as altered gut morphology (shortened colon length). F1 females showed significant alterations in affective behaviors, including measures of anxiety and depressive-like behaviors, indicating altered development. Analysis of small noncoding RNAs in the sperm of F0 mice revealed that gut microbiome depletion is associated with differential expression of 8 different PIWI-interacting RNAs (piRNAs), each of which has the potential to modulate the expression of multiple downstream gene targets, and thus influence epigenetic inheritance and offspring development. This study demonstrates that the gut-germline axis influences sperm small RNA profiles and offspring physiology, with specific impacts on offspring affective and/or coping behaviors. These findings may have broader implications for other animal species with comparable gut microbiota, intergenerational epigenetics and developmental biology, including humans.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-10-25

Curated date: 2024/10/05

Curator: Wendy640

Revision editor(s): Wendy640, Shulamite

Subjects

Location of subjects: Australia

Host species Species from which microbiome was sampled. Contact us to have more species added.: Mus musculus

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Response to antibiotic Response to antibiotic,response to antibiotic

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Male Mice that received drinking water without any antibiotics.

Group 1 name Corresponds to the case (exposed) group for case-control studies: Male Mice that were administered a cocktail of non-absorbable antibiotics to deplete their gut microbiota

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: This group was defined by the condition where the male mice were exposed to antibiotics, leading to significant depletion of their gut microbiota. This was intended to assess the impact of gut microbiome depletion on their offspring

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: MaAsLin2

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: sex, Confounders controlled for: "cohort" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.cohort

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Signature 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-10-25

Curated date: 2024/10/07

Curator: Wendy640

Revision editor(s): Wendy640, Shulamite

Source: Table 1

Description: Taxas significantly higher in the control group compared to antibiotic treated males after adjusting for cohort effects.

Abundance in Group 1: increased abundance in Male Mice that were administered a cocktail of non-absorbable antibiotics to deplete their gut microbiota

NCBI	Quality Control	Links
Clostridia_UCG_014_61Clostridia_UCG_014_61
Muribaculum_6Muribaculum_6
Muribaculum_19Muribaculum_19
Muribaculum_25Muribaculum_25
Muribaculum_29Muribaculum_29
Muribaculum_42Muribaculum_42
Muribaculum_44Muribaculum_44
Muribaculum_28Muribaculum_28
Muribaculum_49Muribaculum_49
Muribaculum_2Muribaculum_2
Muribaculum_21Muribaculum_21
Muribaculum_7Muribaculum_7
Muribaculum_45Muribaculum_45
Muribaculum_32Muribaculum_32
Muribaculum_39Muribaculum_39

Revision editor(s): Wendy640, Shulamite