Editorial: Innovative Therapeutic Strategies Targeting Early-Life Gut Microbiota: Pathways to Long-Term Health Benefits

Silvia Turroni¹Lorena Coretti²Faiga Magzal³Monica Barone⁴Kenneth J. O'Riordan⁵Francesca Lembo^2*

• ¹Department of Pharmacy and Biotechnology, Universita degli Studi di Bologna, Bologna, Italy
• ²Department of Pharmacy, University of Naples Federico II, Naples, Italy
• ³Department of Nutritional Sciences, Tel-Hai College, Upper Galilee, Israel
• ⁴Department of Medical and Surgical Sciences, Universita degli Studi di Bologna, Bologna, Italy
• ⁵College of Medicine and Health, University College Cork, Cork, Ireland

microbiota to immune mechanisms and prebiotic intervention in AD (https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1400657/full). This collection also includes an observational study underscoring the composition and dynamics of the intestinal microbiota in infants with congenital heart disease (CHD), as well as potential influencing factors. It has been reported that the observed microbial patterns are linked to oxygenation and perfusion in CHD patients shortly after birth (https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1468842/full). A focus on host-microbe immune interactions, employing human-like advanced research models suitable to investigate the impact of commensal microbiota on immune function, has been developed by Liu and collaborators (https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1398631/full). In germ-free and specific-pathogen-free piglets, they observed that commensal microbiota impacted the abundance of various immune cell types and the proliferation and differentiation of lymphocytes. In a different research context focused on neurobehavioral functions during early development, Nankova and collaborators employed a microbiota perturbation model to investigate the underlying mechanisms. Using a mouse model of postnatal antibiotic-induced dysbiosis, they demonstrated that altering the normal seeding and maturation of the postnatal microbiome affected neuroendocrine signaling, stress responses, and behavior in a sex-specific manner, providing mechanistic evidence that microbial composition can shape neurodevelopment (https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1504513/full). The second theme covers approaches to delve into the effects of microbiota remodeling through therapeutic tools. Included studies pinpoint the use of complementary and alternative medical techniques and microbiota-based therapies in human and animal models. Generally, both ozone rectal insufflation and electroacupuncture are being investigated for their modulatory effects on the gut microbiota. Through mechanisms involving the autonomic nervous system, anti-inflammatory pathways, and changes in the intestinal environment, these nonpharmacological interventions may influence microbial composition and host-microbe interactions, especially during early development or in dysbiotic conditions. In an experimental model of atherosclerosis (ApoE-/-mice on a high-fat diet), ozone rectal insufflation was found to reduce plaque formation and serum low-density lipoprotein cholesterol levels, likely through an improvement in gut microbial health and regulation of microbial metabolites (https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1597695/full). In a rat model of perinatal nicotine exposure (PNE), electroacupuncture in the dams reduced the PNEinduced impairment of lung development in the offspring (https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1465673/full). This effect was shown to be mediated by microbiota functions, since maternal antibiotic treatment blocked the beneficial effects of electroacupuncture on pulmonary function and lung morphology in offspring. Treatments able to support an eubiotic trajectory of microbiota colonization in neonates and preterm infants, and manage various dysbiosis-related diseases, are under study. Among these, probiotic supplementation is gathering attention as an adjunct therapy to manage neonatal gut health and recovery from diverse neonatal diseases. Probiotic-based complementary therapies, namely supplementation with Clostridium butyricum and Bifidobacterium infantis, were shown to ameliorate antibiotic-mediated dysbiosis in preterm infants with neonatal respiratory distress syndrome, contributing to disease recovery (https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1544055/full). wo Research studies by Hudcovic and Yoon and collaborators to shape host diseases outcomes (https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1440134/full) demonstrated the importance of probiotic-based therapies in early life to establish the correct microbiota signature and promote long-term health benefits, including protection from later pathological events. In animal models, the researchers specifically focused on a probiotic intervention aimed at protecting against intestinal inflammation (inflammatory colitis and enterotoxigenic Escherichia coli, ETEC, infection, respectively). Experiments in gnotobiotic mice showed that susceptibility to colitis was determined by the order of colonization by probiotic versus pathogenic E. coli strains, emphasizing the importance of microbial priority effects to shape host outcomes (https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1393732/full). Also, Yoon et al. identified Lactiplantibacillus argentoratensis as a novel probiotic candidate that protects against ETEC infection, enhances barrier integrity, and promotes short-chain fatty acid production (https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1440134/full). In conclusion, the articles included in this Research Topic help to shed light on the role of the gut microbiota in early development, its link to pathophysiological states and predisposition to disease, and the therapeutic opportunities of modifying aberrant microbiota structures to impact long-term health outcomes. As gut microbiota not only determines gut health, but also regulates systemic development affecting the nervous, respiratory, cardiovascular, metabolic, and immune systems, it is essential to strengthen our understanding of its role in shaping future health. This is particularly important from the earliest stages of development, given its early integration as a key modulator of the host's response capacity. We thank all contributing authors for their valuable efforts, and we hope this collection inspires further exploration and innovation at the intersection of microbiota, development, and health.