Biology subjects

Fast, D.

Publications and source records attributed to Fast, D..

4 recordsLinked to original sources

bioRxiv2025

The gut microbiota and sleep in infants: a focus on diurnal rhythmicity patterns

Emerging evidence supports a bidirectional relationship between the gut microbiome and sleep, partly mediated by the microbiota-gut-brain axis. Circadian rhythms appear to influence early developmental processes and may play a role in shaping this relationship. While infancy is a critical window for both gut microbiota establishment and the maturation of sleep regulation, the role of gut bacteria in modulating infant sleep remains poorly understood. In this longitudinal study, we performed continuous within-subject sampling (monitoring across 48 hours) in 20 infants at 2, 4, and 6 months of age to examine associations between the establishment of gut microbiota and sleep patterns. We hypothesized that microbial diversity and sleep rhythmicity would be linked across both short (diurnal) and long (monthly) time scales. Gut microbiota profiles were characterized using 16S rRNA gene sequencing; gut melatonin concentrations were measured; and sleep metrics were quantified through wearable actimetry, parent-reported 24-hour sleep diaries, and the Brief Infant Sleep Questionnaire (BISQ). Parents additionally completed the Baby Care Questionnaire (BCQ), assessing parenting style, and the Ages and Stages Questionnaire (ASQ), evaluating infant behavioral development. In some infants, alpha diversity followed diurnal rhythmic patterns. Although bacterial rhythmicity was not significantly associated with sleep rhythmicity, as quantified with the Circadian Function Index, infants with higher alpha diversity had more robust sleep rhythmicity ({beta}Faith PD= 0.0721, SE = 0.0337). Infant age emerged as the strongest predictor of both gut microbiota diversity (observed features: {beta}age = 0.101, SE = 0.0172) and gut melatonin concentrations ({beta}age = 0.638, SE = 0.162). For the same age, gut microbiota temporal volatility - an indicator for bacterial community instability - was not associated with sleep patterns. This study demonstrates promising short- and long-term links between gut microbiota diversity and sleep-wake rhythm maturation in infancy. Further research is needed to elucidate the mechanistic role of the gut microbiome in sleep development.

microbiology↗

bioRxiv2019

Symbiotic Lactobacillus brevis promote stem cell expansion and tumorigenesis in the Drosophila intestine.

Microbial factors influence homeostatic and oncogenic growth in the intestinal epithelium. However, we know little about immediate effects of commensal bacteria on stem cell division programs. In this study, we examined effects of commensal Lactobacillus species on homeostatic, and tumorigenic stem cell growth in the Drosophila intestine. We identified Lactobacillus brevis as a potent stimulator of stem cell growth. In a wildtype midgut, Lactobacillus brevis activates growth regulatory pathways that drive stem cell divisions. In a Notch-deficient background, Lactobacillus brevis-mediated growth causes rapid expansion of mutant progenitors, leading to accumulation of large, multi-layered tumors throughout the midgut. Mechanistically, we showed that Lactobacillus brevis disrupts expression and subcellular distribution of progenitor cell integrins, supporting symmetric divisions that expand intestinal stem cell populations. Collectively, our data emphasize the impact of commensal microbes on growth and maintenance of the intestinal progenitor compartment.

cell biology↗

bioRxiv2019

Complex symbiont-pathogen interactions inhibit intestinal repair

Pathogen-mediated damage to the intestinal epithelium activates compensatory growth and differentiation repair programs in progenitor cells. Accelerated progenitor growth replenishes damaged tissue and maintains barrier integrity. Despite the importance of epithelial renewal to intestinal homeostasis, we know little about the effects of pathogen-commensal interactions on progenitor growth. We found that the enteric pathogen Vibrio cholerae, blocks critical growth and differentiation pathways in Drosophila progenitors despite extensive damage to the epithelial tissue. We showed that inhibition of epithelial repair requires interactions of the Vibrio cholerae type six secretion system with a complex community of symbiotic bacteria, and that elimination of the gut microbiome is sufficient to restore homeostatic growth in infected intestines. Together, this work highlights the importance of pathogen-symbiont interactions on intestinal immune responses and outlines a previously undescribed impact of the type six secretion system on pathogenesis.

immunology↗

bioRxiv2018

Commensal-Pathogen Competition Impacts Host Viability

While the structure and regulatory networks that govern the activity of the type-six secretion system (T6SS) of Vibrio cholerae are becoming increasingly clear, we know less about the role of the T6SS in disease. Under laboratory conditions, V. cholerae uses the T6SS to outcompete many Gram-negative species, including other V. cholerae strains and human commensal bacteria. However, the role of these interactions has not been resolved in an in-vivo setting. We used the Drosophila melanogaster model of cholera to define the contribution of the T6SS to V. cholerae pathogenesis. Here, we demonstrate that interactions between the T6SS and host commensals impact pathogenesis. Inactivation of the T6SS, or removal of commensal bacteria attenuates disease severity. Re-introduction of the Gram-negative commensal bacterium Acetobacter pasteurianus into a germ-free host is sufficient to restore T6SS-dependent pathogenesis. Together, our data demonstrate that the T6SS acts on commensal bacteria to promote the pathogenesis of V. cholerae.

microbiology↗