Melatonin-mediated corrective changes in gut microbiota of experimentally chronodisrupted C57BL/6J mice

ABSTRACT

Chronic consumption of a high-calorie diet coupled with an altered sleep-wake cycle causes disruption of circadian clock that can impact the gut microbiome leading to metabolic syndrome and associated diseases. Herein, we investigate the effects of a high fat high fructose diet (H) alone or in combination with photoperiodic shifts induced chronodisruption (CD) on gut microbiota of C57BL/6J male mice. Further, the merits of daily evening intraperitoneal administration of melatonin in restoring gut microbiota are studied herein. Experimental groups viz. H, CD and HCD mice recorded higher levels of serum pro-inflammatory cytokines (TNF-α and IL-6) and lower levels of the anti-inflammatory cytokine, IL-10. These findings correlate with a concomitant increase in the transcripts of TLR4, TNF-α, and IL-6 in small intestine of the said groups. A decrement in mRNA levels of Ocln, ZO-1 and Vdr in these groups implied towards an altered gut permeability. These results were in agreement with the observed decrement in percentage abundance of total gut microflora and Firmicutes: Bacteroidetes (F/B) ratio. Melatonin administration accounted for lower-level inflammation (serum and gut) along with an improvement in gut permeability markers. The total abundance of gut microflora and F/B ratio showed an improvement in all the melatonin-treated groups and the same is the highlight of this study. Taken together, our study is the first to report perturbations in gut microbiota resulting due to a combination of photoperiodic shifts induced CD and a high fat high calorie diet-induced lifestyle disorder. Further, melatonin-mediated rejuvenation of gut microbiome provides prima facie evidence of its role in improving gut dysbiosis that needs a detailed scrutiny.

KEYWORDS:

• Melatonin
• gut microbiota
• photoperiod
• chronodisruption
• high fat-high fructose diet
• inflammation

Acknowledgments

This work was supported by the Department of Biotechnology (DBT) (BT/PR36169/MED/30/2197/2020). A.V. acknowledges DST-PURSE for providing junior research fellowship. R.K. and S.K. acknowledge Lady Tata Memorial Trust (LTMT) and Indian Council of Medical Research (ICMR) for providing JRF and SRF respectively.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

A.V. and R.D. contributed to the study design; R.D. obtained funding; A.V. and H.V. performed animal experimentation; A.V., H.V., R.K., S.K., and M.D. performed the molecular biology experiments; A.V., K.K.U., P.K., and R.D. analysed the data; A.V., S.K., and R.D. wrote the manuscript. All authors reviewed the final manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/07420528.2024.2329205.

Additional information

Funding

Department of Biotechnology (DBT), Government of India, Grant/Award number: [BT/PR36169/MED/30/2197/2020].