Differential Methylation Profile in Fragile X Syndrome-Prone Offspring Mice after in Utero Exposure to Lactobacillus Reuteri
Environmental factors such as diet, gut microbiota, and infections have proven to have a significant role in epigenetic modifications. It is known that epigenetic modifications may cause behavioral and neuronal changes observed in neurodevelopmental disabilities, including fragile X syndrome (FXS) a...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/8/1300 |
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| author | Reem R. AlOlaby Marwa Zafarullah Mariana Barboza Gang Peng Bernard J. Varian Susan E. Erdman Carlito Lebrilla Flora Tassone |
| author_facet | Reem R. AlOlaby Marwa Zafarullah Mariana Barboza Gang Peng Bernard J. Varian Susan E. Erdman Carlito Lebrilla Flora Tassone |
| author_sort | Reem R. AlOlaby |
| collection | DOAJ |
| description | Environmental factors such as diet, gut microbiota, and infections have proven to have a significant role in epigenetic modifications. It is known that epigenetic modifications may cause behavioral and neuronal changes observed in neurodevelopmental disabilities, including fragile X syndrome (FXS) and autism (ASD). Probiotics are live microorganisms that provide health benefits when consumed, and in some cases are shown to decrease the chance of developing neurological disorders. Here, we examined the epigenetic outcomes in offspring mice after feeding of a probiotic organism, <i>Lactobacillus reuteri</i> (<i>L. reuteri</i>), to pregnant mother animals. In this study, we tested a cohort of Western diet-fed descendant mice exhibiting a high frequency of behavioral features and lower FMRP protein expression similar to what is observed in FXS in humans (described in a companion manuscript in this same GENES special topic issue). By investigating 17,735 CpG sites spanning the whole mouse genome, we characterized the epigenetic profile in two cohorts of mice descended from mothers treated and non-treated with <i>L. reuteri</i> to determine the effect of prenatal probiotic exposure on the prevention of FXS-like symptoms. We found several genes involved in different neurological pathways being differentially methylated (<i>p</i> ≤ 0.05) between the cohorts. Among the key functions, synaptogenesis, neurogenesis, synaptic modulation, synaptic transmission, reelin signaling pathway, promotion of specification and maturation of neurons, and long-term potentiation were observed. The results of this study are relevant as they could lead to a better understanding of the pathways involved in these disorders, to novel therapeutics approaches, and to the identification of potential biomarkers for early detection of these conditions. |
| first_indexed | 2024-03-09T04:25:04Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T04:25:04Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-9e7fe55253cb46bdaef54d066d4e00b42023-12-03T13:42:27ZengMDPI AGGenes2073-44252022-07-01138130010.3390/genes13081300Differential Methylation Profile in Fragile X Syndrome-Prone Offspring Mice after in Utero Exposure to Lactobacillus ReuteriReem R. AlOlaby0Marwa Zafarullah1Mariana Barboza2Gang Peng3Bernard J. Varian4Susan E. Erdman5Carlito Lebrilla6Flora Tassone7Department of Mathematics & Sciences, College of Health Sciences, California Northstate University, Sacramento, CA 95670, USABiochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA 95817, USABiochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA 95817, USADepartment of Biostatistics, Yale University School of Public Health, New Haven, CT 06510, USADivision of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USADivision of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USABiochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA 95817, USABiochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA 95817, USAEnvironmental factors such as diet, gut microbiota, and infections have proven to have a significant role in epigenetic modifications. It is known that epigenetic modifications may cause behavioral and neuronal changes observed in neurodevelopmental disabilities, including fragile X syndrome (FXS) and autism (ASD). Probiotics are live microorganisms that provide health benefits when consumed, and in some cases are shown to decrease the chance of developing neurological disorders. Here, we examined the epigenetic outcomes in offspring mice after feeding of a probiotic organism, <i>Lactobacillus reuteri</i> (<i>L. reuteri</i>), to pregnant mother animals. In this study, we tested a cohort of Western diet-fed descendant mice exhibiting a high frequency of behavioral features and lower FMRP protein expression similar to what is observed in FXS in humans (described in a companion manuscript in this same GENES special topic issue). By investigating 17,735 CpG sites spanning the whole mouse genome, we characterized the epigenetic profile in two cohorts of mice descended from mothers treated and non-treated with <i>L. reuteri</i> to determine the effect of prenatal probiotic exposure on the prevention of FXS-like symptoms. We found several genes involved in different neurological pathways being differentially methylated (<i>p</i> ≤ 0.05) between the cohorts. Among the key functions, synaptogenesis, neurogenesis, synaptic modulation, synaptic transmission, reelin signaling pathway, promotion of specification and maturation of neurons, and long-term potentiation were observed. The results of this study are relevant as they could lead to a better understanding of the pathways involved in these disorders, to novel therapeutics approaches, and to the identification of potential biomarkers for early detection of these conditions.https://www.mdpi.com/2073-4425/13/8/1300FXSin uteromethylationepigenetics<i>Lactobacillus reuteri</i>ASD |
| spellingShingle | Reem R. AlOlaby Marwa Zafarullah Mariana Barboza Gang Peng Bernard J. Varian Susan E. Erdman Carlito Lebrilla Flora Tassone Differential Methylation Profile in Fragile X Syndrome-Prone Offspring Mice after in Utero Exposure to Lactobacillus Reuteri Genes FXS in utero methylation epigenetics <i>Lactobacillus reuteri</i> ASD |
| title | Differential Methylation Profile in Fragile X Syndrome-Prone Offspring Mice after in Utero Exposure to Lactobacillus Reuteri |
| title_full | Differential Methylation Profile in Fragile X Syndrome-Prone Offspring Mice after in Utero Exposure to Lactobacillus Reuteri |
| title_fullStr | Differential Methylation Profile in Fragile X Syndrome-Prone Offspring Mice after in Utero Exposure to Lactobacillus Reuteri |
| title_full_unstemmed | Differential Methylation Profile in Fragile X Syndrome-Prone Offspring Mice after in Utero Exposure to Lactobacillus Reuteri |
| title_short | Differential Methylation Profile in Fragile X Syndrome-Prone Offspring Mice after in Utero Exposure to Lactobacillus Reuteri |
| title_sort | differential methylation profile in fragile x syndrome prone offspring mice after in utero exposure to lactobacillus reuteri |
| topic | FXS in utero methylation epigenetics <i>Lactobacillus reuteri</i> ASD |
| url | https://www.mdpi.com/2073-4425/13/8/1300 |
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