Intestinal microbial circadian rhythms drive sex differences in host immunity and metabolism

Munyoki, Sarah K.; Goff, Julie P.; Kolobaric, Antonija; Long, Armari; Mullett, Steven J.; Burns, Jennifer K.; Jenkins, Aaron K.; DePoy, Lauren; Wendell, Stacy G.; McClung, Colleen A.; Morrison, Kathleen E.; Jašarević, Eldin

doi:10.1016/j.isci.2023.107999

Cited by 3 publications

(1 citation statement)

References 114 publications

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“…Here, using 16S rRNA sequencing and metagenomic approaches, we observed that DCM-induced dysbiosis in male was more pronounced that in the females. Along this line, a recent study has shown that changes in microbiota composition and metabolites can influence sex differences in circadian rhythms genes related to the immune system (Munyoki et al, 2023). Thus, it is tempting to suggest that gut dysbiosis might play a role here.…”

Section: Discussionmentioning

confidence: 95%

Degenerative Cervical Myelopathy induces sex-specific dysbiosis in mice

Farkas,

Retamal-Fredes,

Ávila

et al. 2023

Front. Microbiol.

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Degenerative Cervical Myelopathy (DCM) is the most common cause of spinal cord impairment in elderly populations. It describes a spectrum of disorders that cause progressive spinal cord compression, neurological impairment, loss of bladder and bowel functions, and gastrointestinal dysfunction. The gut microbiota has been recognized as an environmental factor that can modulate both the function of the central nervous system and the immune response through the microbiota-gut-brain axis. Changes in gut microbiota composition or microbiota-producing factors have been linked to the progression and development of several pathologies. However, little is known about the potential role of the gut microbiota in the pathobiology of DCM. Here, DCM was induced in C57BL/6 mice by implanting an aromatic polyether material underneath the C5-6 laminae. The extent of DCM-induced changes in microbiota composition was assessed by 16S rRNA sequencing of the fecal samples. The immune cell composition was assessed using flow cytometry. To date, several bacterial members have been identified using BLAST against the largest collection of metagenome-derived genomes from the mouse gut. In both, female and males DCM caused gut dysbiosis compared to the sham group. However, dysbiosis was more pronounced in males than in females, and several bacterial members of the families Lachnospiraceae and Muribaculaceae were significantly altered in the DCM group. These changes were also associated with altered microbe-derived metabolic changes in propionate-, butyrate-, and lactate-producing bacterial members. Our results demonstrate that DCM causes dynamic changes over time in the gut microbiota, reducing the abundance of butyrate-producing bacteria, and lactate-producing bacteria to a lesser extent. Genome-scale metabolic modeling using gapseq successfully identified pyruvate-to-butanoate and pyruvate-to-propionate reactions involving genes such as Buk and ACH1, respectively. These results provide a better understanding of the sex-specific molecular effects of changes in the gut microbiota on DCM pathobiology.

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Section: Discussionmentioning

confidence: 95%

Degenerative Cervical Myelopathy induces sex-specific dysbiosis in mice

Farkas,

Retamal-Fredes,

Ávila

et al. 2023

Front. Microbiol.

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Chemical interplay between gut microbiota and epigenetics: Implications in circadian biology

Sharma,

Oladejo,

Kuang

2024

Cell Chemical Biology

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The microbiota extends the reproductive lifespan by safeguarding the ovarian reserve

Munyoki,

Goff,

Reshke

et al. 2024

Preprint

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Infertility is a devastating condition affecting one in six people globally. In many cases, the underlying causes are unknown. Emerging evidence suggests that the microbiota influences reproduction, yet the mechanistic link between the microbiota, ovarian function, and length of the fertile lifespan remain unexplored. Here we report that the microbiota controls the length of the reproductive lifespan by maintaining the primordial follicle pool, a process mediated by microbiota-derived short chain fatty acids modulating gene regulatory networks crucial for the survival of the ovarian reserve. Dietary perturbation of the microbiota during a critical developmental window is sufficient to diminish the ovarian reserve, reduce oocyte retrieval, and impair preimplantation embryo viability, mirroring challenges in human fertility treatments. Targeted interventions to restore microbiota improve assisted reproductive outcomes, particularly when implemented early. These findings reveal a novel contribution of host-microbe interactions in mammalian reproduction and demonstrate that the microbiota impacts ovarian function and fertility.

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Intestinal microbial circadian rhythms drive sex differences in host immunity and metabolism

Cited by 3 publications

References 114 publications

Degenerative Cervical Myelopathy induces sex-specific dysbiosis in mice

Degenerative Cervical Myelopathy induces sex-specific dysbiosis in mice

Chemical interplay between gut microbiota and epigenetics: Implications in circadian biology

The microbiota extends the reproductive lifespan by safeguarding the ovarian reserve

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