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<p>Disturbances in circadian rhythm and internal desynchronization are increasingly associated with various neurological health conditions, highlighting the need for effective therapeutic interventions. In the present study, we hypothesized a strong correlation between Prebiotics-Gut Microbiota-Circadian Rhythm, capable of influencing host neurochemical and physiological homeostasis. The effects of a synbiotic formulation comprising a well-characterized xylooligosaccharide (XOS) and <i>Lactobacillus rhamnosus</i> on circadian rhythm regulation in a Caco-2 cell model were investigated. The synbiotic treatment, effectively ameliorated disturbed circadian rhythm in Caco-2 cells and improved neurological internal synchronization through the modulation of neuroactive molecules, which was confirmed by the RT-PCR gene expression studies and transcriptome analysis. Among 73 circadian rhythm regulatory genes, 34 genes showed recovery toward normal expression levels, including PER1, <i>PER2</i>, <i>CRY1</i>, <i>CRY2</i>, and <i>DBP</i>. Furthermore, transcriptomic profiling revealed a significant recovery of neurotransmitter-related genes (<i>DDC</i>, <i>TPH1</i>, <i>COMT</i>, <i>MAOA</i>), suggesting a mechanistic link between circadian recovery and neurochemical pathways. Analysis of gut microbiota-derived metabolites demonstrated increased levels of serotonin, dopamine, and GABA in the treated Caco-2 cells, supporting the role of microbial metabolites in modulating host circadian rhythm. The findings indicate that XOS plays a central role not only as a prebiotic but also as a functional carbohydrate capable of influencing host chronobiology through gut microbiota interactions. These findings provide valuable insights into the complex interplay between circadian rhythm gene regulation and microbial metabolites. The results advance our understanding of the structure–function relationship of XOS in health applications and highlight its promise in developing targeted interventions for circadian rhythm-associated disorders.</p> Graphical abstract <p></p>

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Xylooligosaccharide in combination with Lactobacillus rhamnosus ameliorates disturbed circadian rhythm and associated neurological internal desynchronization by maintaining homeostasis of neuroactive molecules and gut microbiome

  • 期刊论文

  • 发表日期：

    2026年2月19日

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  • Rutuja Murlidhar Sonkar,
  • Pravin Savata Gade,
  • Praveena Bhatt

摘要

Disturbances in circadian rhythm and internal desynchronization are increasingly associated with various neurological health conditions, highlighting the need for effective therapeutic interventions. In the present study, we hypothesized a strong correlation between Prebiotics-Gut Microbiota-Circadian Rhythm, capable of influencing host neurochemical and physiological homeostasis. The effects of a synbiotic formulation comprising a well-characterized xylooligosaccharide (XOS) and Lactobacillus rhamnosus on circadian rhythm regulation in a Caco-2 cell model were investigated. The synbiotic treatment, effectively ameliorated disturbed circadian rhythm in Caco-2 cells and improved neurological internal synchronization through the modulation of neuroactive molecules, which was confirmed by the RT-PCR gene expression studies and transcriptome analysis. Among 73 circadian rhythm regulatory genes, 34 genes showed recovery toward normal expression levels, including PER1, PER2, CRY1, CRY2, and DBP. Furthermore, transcriptomic profiling revealed a significant recovery of neurotransmitter-related genes (DDC, TPH1, COMT, MAOA), suggesting a mechanistic link between circadian recovery and neurochemical pathways. Analysis of gut microbiota-derived metabolites demonstrated increased levels of serotonin, dopamine, and GABA in the treated Caco-2 cells, supporting the role of microbial metabolites in modulating host circadian rhythm. The findings indicate that XOS plays a central role not only as a prebiotic but also as a functional carbohydrate capable of influencing host chronobiology through gut microbiota interactions. These findings provide valuable insights into the complex interplay between circadian rhythm gene regulation and microbial metabolites. The results advance our understanding of the structure–function relationship of XOS in health applications and highlight its promise in developing targeted interventions for circadian rhythm-associated disorders.

Graphical abstract