Gut microbiota as a modulator of circadian neural development in the honey bee model.
Koru. Yılmaz Berk YB; Beer. Katharina K; Ruggieri. Angelo Alberto AA; Rodríguez-Cordero. Josué Alejandro JA; Aviles-Rios. Evelyn E; Anderson. Maya M; Citron-Rodriguez. Esteban A EA; Montes-Mercado. Airined A; De Jesύs-Cortés. Héctor H; Giannoni-Guzmán. Manuel Antonio MA; Perez Claudio. Eddie E; Courtney. Emma C EC; Andujar-Sierra. Cristina Lee CL; Strubbe-Nieves. Abigail A; Ortiz-Alvarado. Yarira Y; Döke. Mehmet Ali MA; Ortiz-Zuazaga. Humberto H; Moore. Darrell D; Giordano. Rosanna R; Ghezzi-Grau. Alfredo A; Scheiner. Ricarda R; Giray. Tugrul T; Agosto-Rivera. Jose Luis JL
Key Findings
- Antibiotic‑treated or germ‑free bees have weaker daily activity rhythms than normal bees.
- These bees also have fewer PDF‑expressing clock neurons, indicating delayed circadian system maturation.
- Early antibiotic exposure boosts IGFALS expression, a protein that stabilizes IGF‑1/2, linking gut microbes to IGF signaling.
Practical Outcomes
- For biohackers, the take‑away is that preserving a healthy gut microbiome—especially in early life—could support normal circadian development and IGF‑related neurogrowth. Avoiding unnecessary antibiotics and possibly using probiotic strategies may help maintain optimal IGF‑1 activity and daily rhythm stability.
Summary
A study in honey bees shows that messing with gut bacteria early in life (like using antibiotics) can mess up the development of the internal clock and reduce the number of clock‑related brain cells. The same disruption also raises a protein (IGFALS) that holds onto IGF‑1/2, a hormone important for brain growth. This suggests that early gut health can influence IGF signaling and circadian rhythms, which might matter for humans too.
Abstract
Disruption in gut microbiota during the early postnatal period can disrupt normal neural development and result in long-term behavioral alterations <sup>1</sup> . Similar to other neural systems, the circadian clock mechanism continues to mature after birth <sup>2</sup> , yet how microbial disturbances in the early period influence the onset of circadian rhythms and the development of central clock mechanisms remains poorly understood. Here we studied whether early-life gut dysbiosis affects the ontogeny of behavioral circadian rhythms and the maturation of clock neurons using the honey bee ( <i>Apis mellifera</i> ), a model organism that shares features of postnatal development of behavioral circadian rhythm and clock system <sup>3-5</sup> with humans <sup>6</sup> . Our findings demonstrate that antibiotic-treated and gnotobiotic-reared bees display reduced rhythmicity compared to controls. These treatments also impair the development of the circadian pacemaker, marked by fewer Pigment-Dispersing Factor (PDF)-expressing neurons. Additionally, antibiotic exposure increased the expression of the Insulin-like Growth Factor Binding Protein Acid Labile Subunit ( <i>IGFALS</i> ) in early ages, which stabilizes the IGF-1/2 <sup>7</sup> , a hormone important for neurodevelopmental processes <sup>42</sup> . Together, these results identify gut microbiota as a modulator of circadian development. Our work provides an understanding of how early-life microbial disruptions influence the development of circadian rhythms, providing information that may extend to other animals, including humans.
Study Information
pubmed
2025
2025-10-02T00:00:00.000Z
10.1101/2025.09.30.678393
52