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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Maternal 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, Lactobacillus reuteri, 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 L. reuteri 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 L. reuteri-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.

Details

Title
Maternal Microbiota Modulate a Fragile X-like Syndrome in Offspring Mice
Author
Varian, Bernard J 1   VIAFID ORCID Logo  ; Weber, Katherine T 1   VIAFID ORCID Logo  ; Kim, Lily J 1 ; Chavarria, Tony E 1 ; Carrasco, Sebastian E 1 ; Sureshkumar Muthupalani 1 ; Poutahidis, Theofilos 2 ; Zafarullah, Marwa 3   VIAFID ORCID Logo  ; Al Olaby, Reem R 4 ; Barboza, Mariana 3   VIAFID ORCID Logo  ; Solakyildirim, Kemal 3 ; Lebrilla, Carlito 3   VIAFID ORCID Logo  ; Tassone, Flora 5   VIAFID ORCID Logo  ; Wu, Fuqing 6 ; Alm, Eric J 7 ; Erdman, Susan E 1   VIAFID ORCID Logo 

 Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA 
 Laboratory of Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece 
 Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA 
 College of Health Sciences, California Northstate University, Rancho Cordova, CA 95670, USA 
 Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; MIND Institute, University of California Davis, Sacramento, CA 95817, USA 
 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Center for Infectious Diseases, School of Public Health, The University of Texas Health Science Center, Houston, TX 77030, USA 
 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA 
First page
1409
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
20734425
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2706218382
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.