Researchers have discovered that gut bacteria balance can affect the symptoms of hypopituitarism in mice. Additionally, they found that aspirin can alleviate hormone deficiency symptoms in these mice.
A team from the Francis Crick Institute has demonstrated that gut bacteria balance can impact the symptoms of hypopituitarism in mice.
The researchers also revealed that aspirin helps improve symptoms related to hormone deficiencies in mice affected by this disorder.
Individuals with a mutation in the gene known as Sox3 experience hypopituitarism, where the pituitary gland fails to produce adequate hormones. This deficiency can lead to growth issues, infertility, and an inadequate response to stress.
In a study released today in PLOS Genetics, the researchers at the Crick removed the Sox3 gene from mice, resulting in the onset of hypopituitarism around the time they began eating solid food.
The investigation found that Sox3 mutations significantly impact the hypothalamus, a part of the brain responsible for signaling the pituitary gland to release hormones. However, since this gene is typically active in various brain cells, the first step was to identify which specific cells were most affected by its absence.
The researchers noted a decrease in the population of cells known as NG2 glia, indicating these cells are essential for maturing the hormone-producing cells in the pituitary gland around weaning, a previously unknown role. This could clarify the observed effects on hormone production.
Following this, the team treated the mice with a low dose of aspirin over 21 days. This treatment resulted in an increased count of NG2 glia in the hypothalamus and reversed the hypopituitarism symptoms in the mice.
While the precise mechanism by which aspirin affected this is still unclear, the findings hint that it may offer a potential treatment avenue for individuals with Sox3 mutations or other conditions where NG2 glia are compromised.
An unexpected discovery highlighted the influence of gut bacteria on hormone production.
When the National Institute for Medical Research (NIMR) merged with the Crick in 2015, mouse embryos, including those with Sox3 mutations, were moved to the new facility.
When these mice reached the weaning stage at Crick, researchers were surprised to find that the expected hormonal deficiencies were absent.
After examining various potential causes, lead author Christophe Galichet compared the microbiomes—the collective bacteria, fungi, and viruses living in the gut—of the mice at Crick to those at NIMR and noted significant differences in their composition and diversity. These changes could have resulted from dietary adjustments, water sources, or other environmental factors associated with the relocation.
He also assessed the NG2 glia count in the Crick mice and found that these cells were at normal levels, suggesting that the microbiome from the Crick was somehow protective against hypopituitarism.
To validate this theory, Christophe transplanted fecal matter from NIMR mice into Crick mice, which led to a re-emergence of hypopituitarism symptoms and a reduction in NG2 glia.
While the exact mechanism remains unknown, the researchers concluded that the composition of the gut microbiome exemplifies an essential environmental factor that can significantly affect the outcomes of genetic mutations, particularly influencing the function of the hypothalamus and pituitary gland.
Christophe Galichet, who was a Senior Laboratory Research Scientist at the Crick and is now the Research Operations Manager at the Sainsbury Wellcome Centre, stated: “It was astonishing to discover that changes in the gut microbiome could reverse hypopituitarism in mice lacking Sox3. This emphasizes the importance of considering all variables, including the microbiome, when conducting animal research and how nurture can impact nature.”
Robin Lovell-Badge, Group Leader in the Stem Cell Biology and Developmental Genetics Laboratory at the Crick, added: “Hypopituitarism can arise from trauma as well as rare genetic mutations, and it can profoundly affect overall health. Our research not only suggests potential treatment options but also highlights the significance of the gut-brain connection. The next phase of this study will focus on determining how aspirin and the microbiome affect NG2 glia, followed by efforts to study these effects in humans to see if these accessible interventions can assist in treating hypopituitarism.”
