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dc.contributor.authorVarian, Bernard J.
dc.contributor.authorWeber, Katherine T.
dc.contributor.authorKim, Lily J.
dc.contributor.authorChavarria, Tony E.
dc.contributor.authorCarrasco, Sebastian E.
dc.contributor.authorMuthupalani, Sureshkumar
dc.contributor.authorPoutahidis, Theofilos
dc.contributor.authorZafarullah, Marwa
dc.contributor.authorAl Olaby, Reem R.
dc.contributor.authorBarboza, Mariana
dc.contributor.authorSolakyildirim, Kemal
dc.contributor.authorLebrilla, Carlito
dc.contributor.authorTassone, Flora
dc.contributor.authorWu, Fuqing
dc.contributor.authorAlm, Eric J.
dc.contributor.authorErdman, Susan E.
dc.date.accessioned2022-08-11T12:12:20Z
dc.date.available2022-08-11T12:12:20Z
dc.date.issued2022-08-08
dc.identifier.urihttps://hdl.handle.net/1721.1/144309
dc.description.abstractMaternal microbial dysbiosis has been implicated in adverse postnatal health conditions in offspring, such as obesity, cancer, and neurological disorders. We observed that the progeny of mice fed a Westernized diet (WD) with low fiber and extra fat exhibited higher frequencies of stereotypy, hyperactivity, cranial features and lower FMRP protein expression, similar to what is typically observed in Fragile X Syndrome (FXS) in humans. We hypothesized that gut dysbiosis and inflammation during pregnancy influenced the prenatal uterine environment, leading to abnormal phenotypes in offspring. We found that oral in utero supplementation with a beneficial anti-inflammatory probiotic microbe, <i>Lactobacillus reuteri</i>, was sufficient to inhibit FXS-like phenotypes in offspring mice. Cytokine profiles in the pregnant WD females showed that their circulating levels of pro-inflammatory cytokine interleukin (Il)-17 were increased relative to matched gravid mice and to those given supplementary <i>L. reuteri</i> probiotic. To test our hypothesis of prenatal contributions to this neurodevelopmental phenotype, we performed Caesarian (C-section) births using dissimilar foster mothers to eliminate effects of maternal microbiota transferred during vaginal delivery or nursing after birth. We found that foster-reared offspring still displayed a high frequency of these FXS-like features, indicating significant in utero contributions. In contrast, matched foster-reared progeny of <i>L. reuteri</i>-treated mothers did not exhibit the FXS-like typical features, supporting a key role for microbiota during pregnancy. Our findings suggest that diet-induced dysbiosis in the prenatal uterine environment is strongly associated with the incidence of this neurological phenotype in progeny but can be alleviated by addressing gut dysbiosis through probiotic supplementation.en_US
dc.publisherMultidisciplinary Digital Publishing Instituteen_US
dc.relation.isversionofhttp://dx.doi.org/10.3390/genes13081409en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceMultidisciplinary Digital Publishing Instituteen_US
dc.titleMaternal Microbiota Modulate a Fragile X-like Syndrome in Offspring Miceen_US
dc.typeArticleen_US
dc.identifier.citationGenes 13 (8): 1409 (2022)en_US
dc.contributor.departmentMassachusetts Institute of Technology. Division of Comparative Medicine
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineering
dc.identifier.mitlicensePUBLISHER_CC
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2022-08-11T11:49:56Z
dspace.date.submission2022-08-11T11:49:56Z
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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