Microbiome affects mice metabolic homeostasis via differential regulation of gene expression in the brain and gut
Abstract The gut microbiome (GMB) regulates digestion, metabolism, immunity, and energy homeostasis. This study investigates how gut microbiota integrate the regulation in the neuroendocrine and enteroendocrine systems, with a focus on G protein‐coupled receptors (GPCRs) in the brain‐gut axis and se...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.70373 |
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| author | Wynne Milhouse Anna Clapp Organski Xun Sun Derek Ai Baohua Zhou Tzu‐Wen L. Cross Hongxia Ren |
| author_facet | Wynne Milhouse Anna Clapp Organski Xun Sun Derek Ai Baohua Zhou Tzu‐Wen L. Cross Hongxia Ren |
| author_sort | Wynne Milhouse |
| collection | DOAJ |
| description | Abstract The gut microbiome (GMB) regulates digestion, metabolism, immunity, and energy homeostasis. This study investigates how gut microbiota integrate the regulation in the neuroendocrine and enteroendocrine systems, with a focus on G protein‐coupled receptors (GPCRs) in the brain‐gut axis and sex differences. Germ‐free (GF) mice exhibited increased hypothalamic expression of the anorexigenic neuropeptide and decreased expression of the negative regulator of leptin signaling. GF males had significantly lower serum leptin levels compared to conventional (CON) males, highlighting a potential link between the microbiome and leptin resistance. In the gut, GF mice demonstrated heightened expression of anorexigenic gut hormones, including peptide YY (Pyy) and cholecystokinin (Cck), in addition to increased levels of G protein‐coupled receptors (GPCRs) involved in gut hormone secretion and nutrient metabolism, particularly in females. While carbohydrate metabolism genes were upregulated in CON mice, lipid metabolism genes were predominantly higher in GF mice. These findings suggest that the gut microbiota downregulates genes involved in appetite suppression, modulates GPCRs linked to gut hormone secretion, and contributes to leptin resistance, particularly in males. This research underscores the importance of the gut microbiome in host metabolism and reveals potential molecular targets for novel treatments of metabolic diseases. |
| format | Article |
| id | doaj-art-4eb24fce5e5f4c4b9bea960e441cd780 |
| institution | Kabale University |
| issn | 2051-817X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-4eb24fce5e5f4c4b9bea960e441cd7802025-08-20T04:27:55ZengWileyPhysiological Reports2051-817X2025-05-011310n/an/a10.14814/phy2.70373Microbiome affects mice metabolic homeostasis via differential regulation of gene expression in the brain and gutWynne Milhouse0Anna Clapp Organski1Xun Sun2Derek Ai3Baohua Zhou4Tzu‐Wen L. Cross5Hongxia Ren6Department of Pediatrics Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine Indianapolis Indiana USADepartment of Nutrition Science Purdue University West Lafayette Indiana USADepartment of Pediatrics Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine Indianapolis Indiana USACenter for Diabetes and Metabolic Disease Indiana University School of Medicine Indianapolis Indiana USADepartment of Pediatrics Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine Indianapolis Indiana USADepartment of Nutrition Science Purdue University West Lafayette Indiana USADepartment of Pediatrics Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine Indianapolis Indiana USAAbstract The gut microbiome (GMB) regulates digestion, metabolism, immunity, and energy homeostasis. This study investigates how gut microbiota integrate the regulation in the neuroendocrine and enteroendocrine systems, with a focus on G protein‐coupled receptors (GPCRs) in the brain‐gut axis and sex differences. Germ‐free (GF) mice exhibited increased hypothalamic expression of the anorexigenic neuropeptide and decreased expression of the negative regulator of leptin signaling. GF males had significantly lower serum leptin levels compared to conventional (CON) males, highlighting a potential link between the microbiome and leptin resistance. In the gut, GF mice demonstrated heightened expression of anorexigenic gut hormones, including peptide YY (Pyy) and cholecystokinin (Cck), in addition to increased levels of G protein‐coupled receptors (GPCRs) involved in gut hormone secretion and nutrient metabolism, particularly in females. While carbohydrate metabolism genes were upregulated in CON mice, lipid metabolism genes were predominantly higher in GF mice. These findings suggest that the gut microbiota downregulates genes involved in appetite suppression, modulates GPCRs linked to gut hormone secretion, and contributes to leptin resistance, particularly in males. This research underscores the importance of the gut microbiome in host metabolism and reveals potential molecular targets for novel treatments of metabolic diseases.https://doi.org/10.14814/phy2.70373brain‐gut axisdiabetesendocrineGIGPCRintegrative |
| spellingShingle | Wynne Milhouse Anna Clapp Organski Xun Sun Derek Ai Baohua Zhou Tzu‐Wen L. Cross Hongxia Ren Microbiome affects mice metabolic homeostasis via differential regulation of gene expression in the brain and gut Physiological Reports brain‐gut axis diabetes endocrine GI GPCR integrative |
| title | Microbiome affects mice metabolic homeostasis via differential regulation of gene expression in the brain and gut |
| title_full | Microbiome affects mice metabolic homeostasis via differential regulation of gene expression in the brain and gut |
| title_fullStr | Microbiome affects mice metabolic homeostasis via differential regulation of gene expression in the brain and gut |
| title_full_unstemmed | Microbiome affects mice metabolic homeostasis via differential regulation of gene expression in the brain and gut |
| title_short | Microbiome affects mice metabolic homeostasis via differential regulation of gene expression in the brain and gut |
| title_sort | microbiome affects mice metabolic homeostasis via differential regulation of gene expression in the brain and gut |
| topic | brain‐gut axis diabetes endocrine GI GPCR integrative |
| url | https://doi.org/10.14814/phy2.70373 |
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