Exclusive breastfeeding (EBF) plays a crucial role in infant gut microbiome assembly and development. However, few studies have investigated the effects of EBF in restoring a perturbed microbiome. In this study, we applied whole metagenomic sequencing to assess the gut microbiome assembly in 525 Brazilian infants from 3 to 9 months of age of the Germina Cohort, demonstrating the early determinants of microbial taxonomy and function modulation. Our analysis shows that EBF alters the relative abundance of genes related to the microbiome taxonomy and function, with effects varying by delivery mode. EBF alters the pattern of carbohydrates, lipid metabolism, and cell structure pathways depending on the delivery mode. The microbiome age is closer to chronological infant age in EBF than in non-EBF infants, meaning a lower microbiome maturation index (MMI). Using a complementary machine learning approach, we show that Escherichia coli, Ruminococcus gnavus, and Clostridium neonatale, as well as vitamin K and o-antigen pathways contribute strongly to EBF prediction. Moreover, EBF influences the microbiome maturation in early life, toward a microbiome age more similar to the chronological infant's age.

The development of the gut microbiome is crucial to human health, particularly during the first three years of life. Given its role in immune development, disturbances in the establishment process of the gut microbiome may have long term consequences. This review summarizes evidence for these claims, highlighting compositional changes of the gut microbiome during this critical period of life as well as factors that affect gut microbiome development. Based on human and animal data, we conclude that the early-life microbiome is a determinant of long-term health, impacting physiological, metabolic, and immune processes. The early-life gut microbiome field faces challenges. Some of these challenges are technical, such as lack of standardized stool collection protocols, inconsistent DNA extraction methods, and outdated sequencing technologies. Other challenges are methodological: small sample sizes, lack of longitudinal studies, and poor control of confounding variables. To address these limitations, we advocate for more robust research methodologies to better understand the microbiome's role in health and disease. Improved methods will lead to more reliable microbiome studies and a deeper understanding of its impact on health outcomes.

Asthma is a chronic disease affecting millions of children worldwide, and in severe cases requires hospitalization. The etiology of asthma is multifactorial, caused by both genetic and environmental factors. In recent years, the role of the early-life gut microbiome in relation to asthma has become apparent, supported by an increasing number of population studies, in vivo research, and intervention trials. Numerous early-life factors, which for decades have been associated with the risk of developing childhood asthma, are now being linked to the disease through alterations of the gut microbiome. These factors include cesarean birth, antibiotic use, breastfeeding, and having siblings or pets, among others. Association studies have highlighted several specific microbes that are altered in children developing asthma, but these can vary between studies and disease phenotype. This demonstrates the importance of the gut microbial ecosystem in asthma, and the necessity of well-designed studies to validate the underlying mechanisms and guide future clinical applications. In this review, we examine the current literature on the role of the gut microbiome in childhood asthma and identify research gaps to allow for future microbial-focused therapeutic applications in asthma.

Breast milk, rich in human milk oligosaccharides (HMOs), supports the early-life colonization of beneficial bacteria such as bifidobacteria and lactobacilli, potentially reducing early-life antibiotic resistance. However, antibiotic treatment may interfere with the beneficial functions of HMO-degrading bacteria. This study investigated the metabolism of HMOs by bifidobacteria and lactobacilli isolated from human milk and mother-infant paired fecal samples, along with their antibiotic resistance profiles. Understanding these species- and sample-type-specific interactions will provide valuable insights into how bioactive components in human milk may shape the infant resistome during early life. A total of 39 Bifidobacterium and 14 Lactobacillaceae strains were isolated from paired mother-infant fecal and breast milk samples. Whole genome sequencing (WGS) allowed functional predictions on the HMO metabolism abilities and the resistance genotype of each strain. In vitro HMO utilization was assessed using growth kinetics assays combined with HMO glycoprofiling in culture supernatant. The minimum inhibitory concentration (MIC) was also determined for each strain. HMO metabolism by the bifidobacteria was species-specific. Bifidobacterium bifidum (B. bifidum) and Bifidobacterium longum subsp. infantis (B. infantis) exhibited the highest capacity for HMO degradation, consistent with genomic predictions. In contrast, lactobacilli were unable to degrade HMOs in vitro but were predicted to metabolize the by-products of HMO degradation. Phenotypic analysis revealed that B. bifidum strains had the lowest levels of antibiotic resistance, while Bifidobacterium animalis subsp. lactis (B. lactis) strains were resistant to most tested antibiotics. Overall, B. bifidum demonstrated the strongest HMO-degrading ability while remaining the most antibiotic-susceptible species. Early-life colonizing bifidobacterial species possess the essential machinery required to degrade HMOs and are highly susceptible to antibiotics. A better understanding of these dynamics could inform clinical strategies to protect and restore the infant gut microbiome, particularly in neonates exposed to antibiotics.

Diet has a profound impact in human health, which is partly driven by changes in the intestinal microbiota. Several associations between dietary intake and the intestinal microbiota composition and function have been described. Namely, the Mediterranean diet is associated with beneficial bacteria, while the intake of ultraprocessed foods is linked to dysbiosis. It is, therefore, very tempting to tailor dietary approaches to the individual needs of the microbiota; however, high-quality prospective data are lacking. Provisionally, a diet rich in fruits and vegetables and low in ultraprocessed foods is recommended to improve the intestinal microbiota composition and function.

The infant gut microbiome, which develops from birth, has profound and lasting effects on human health. Its establishment in early life is influenced by events such as delivery mode and feeding type. This study examined the effects of formula milk enriched with sn-2 palmitate on the gut microbiota of healthy term infants. We conducted a 16-week comparative analysis of three feeding groups: infants receiving high sn-2 palmitate formula (n = 30), regular vegetable oil formula (n = 32), and breast milk (n = 30). Using shotgun metagenomic sequencing of fecal samples, we performed a comprehensive assessment of the gut microbiota. While overall microbial composition and diversity were comparable across groups, the functional profile of the microbiome in infants receiving sn-2 palmitate-enriched formula more closely resembled that of breastfed infants compared to the control formula group. This similarity extended to microbial species interactions, virulence gene abundance, and metabolic pathway expression patterns. In addition, sn-2 palmitate promoted the proliferation of Bifidobacterium breve and enhanced the robustness of the gut microbial ecology. Notably, the phylogenetic analysis of B. breve strains in the sn-2 palmitate group showed closer alignment with the breastfed group compared to the control group. These findings suggest that sn-2 palmitate-enriched formula may confer gut microbiota functional benefits that more closely resemble those of breast milk compared to control formula milk. This study provides scientific evidence for the development of future functional infant formulas.

The increasing use of assisted reproductive technologies (ART) with donor gametes is driven by rising infertility rates, delayed parenthood, and the need to prevent hereditary diseases. Greater social acceptance of diverse family structures, advancements in reproductive medicine, and improving success rates also contribute. Accessibility, affordability, and cross-border reproductive care further expand ART's reach, making donor gametes a preferred option for many individuals and couples worldwide. The widespread application of ART has led to an increasing number of donor-conceived individuals, many of whom are now reaching reproductive maturity. This demographic shift introduces significant challenges for traditional forensic genetic identification methods, which rely on biological reference samples from genetically related individuals. The absence of such samples complicates the identification process, particularly for individuals conceived via gamete donation or adoption, where biological and legal parentage are incongruent. Conventional forensic genetic analyses, including short tandem repeat (STR) and single nucleotide polymorphism (SNP) profiling of autosomal, Y-chromosome, X-chromosome, and mitochondrial DNA, exhibit limited efficacy in these scenarios. While these methods can sometimes identify individuals conceived using a single donor gamete, they are insufficient for cases involving dual donor gametes or mitochondrial replacement therapy. Emerging methodologies such as forensic genetic genealogy, DNA methylation profiling, and human microbiome analysis offer innovative approaches but necessitate further clinical validation and standardization.

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder that often persists into adulthood, leading to various adverse outcomes. Its underlying pathology is multifactorial, involving neurotransmitter imbalances, gut microbiota alterations, and oxidative and inflammatory dysregulation. Diet, a key environmental modifier of gut ecology, is consistently poorer in individuals with ADHD, with multiple nutrients implicated in its pathophysiology. This review examines the role of specific nutrients such as omega-3 fatty acids, key micronutrients, and potentially harmful dietary components, as well as broader dietary patterns, particularly the Western diet and Mediterranean diet (MedDiet), in relation to ADHD symptoms. It also evaluates both whole-diet and supplement-based clinical interventions, supporting the growing recognition of nutrition as a safe and relatively affordable modifiable factor in ADHD management. Additionally, the biological mechanisms linking diet to ADHD are reviewed, highlighting strong evidence for the involvement of gut dysbiosis and inflammatory processes. Despite the well-documented antioxidant, anti-inflammatory, and microbiome benefits of the MedDiet, direct research investigating its role in ADHD remains limited. Most whole-diet approaches to date have focused on elimination diets, leaving a significant gap in understanding the potential role of the MedDiet in ADHD management. Therefore, this review outlines preliminary evidence supporting the MedDiet and its key components as modulators of ADHD-related biological pathways, indicating its potential as a therapeutic approach. However, further research is required to rigorously evaluate its clinical efficacy. Finally, the limitations of observational and interventional nutritional research in ADHD are discussed, along with recommendations for future research directions.

What enables certain microbes to successfully colonize the mammalian gut? In a recent issue of Cell, Liu et al. present a microbial cross-species genomic framework that identifies conserved genetic determinants of gut residency. This study provides a roadmap for developing more effective microbiome-based therapeutics, advancing our understanding of host-microbe interactions.

The microbiome of adolescents is poorly understood, as are factors influencing its composition. We aimed to describe the healthy adolescent microbiome and identify early-life and concurrent predictors of its composition.

We performed metagenomic sequencing of 247 fecal specimens from 167 adolescents aged 11-14 years participating in the Health Outcomes and Measures of the Environment (HOME) Study, a longitudinal pregnancy and birth cohort (Cincinnati, OH). We described common features of the adolescent gut microbiome and applied self-organizing maps (SOMs)-a machine-learning approach-to identify distinct microbial profiles (n = 4). Using prospectively collected data on sociodemographic characteristics, lifestyle, diet, and sexual maturation, we identified early-life and concurrent factors associated with microbial diversity and phylum relative abundance with linear regression models and composition with Kruskal-Wallis and Fisher's exact tests.

We found that household income and other sociodemographic factors were consistent predictors of the microbiome, with higher income associated with lower diversity and differential relative abundances of Firmicutes (increased) and Actinobacteria (decreased). Sexual maturation, distinct from chronological age, was related to higher diversity in females and differences in phylum relative abundances and compositional profiles in both males and females.

Our study suggests that adolescence is a unique window for gut microbial composition and that it may be shaped by both early-life and concurrent exposures, highlighting its potential in future epidemiologic research.

The initial microbial colonization of the gut is seeded by microbes transmitted from the mother's gut, skin, and vaginal tract. As the gut microbiome evolves, a few transmitted microbes persist throughout life. Understanding the impact of mother-to-neonate gut microbiome and antibiotic resistance genes (ARGs) transmission is crucial for establishing its role in infants' immunity against pathogens.

This study primarily explores mother-neonate ARG transmission through 125 publicly available fecal metagenomes, isolated from eighteen mother-neonate pairs.

The core ARGs, detected in both mothers and their respective infants at all stages (birth, 1st, 2nd, 3rd, 4th, 8th and 12th months) included aminoglycosidases APH(3')-IIIa, Bifidobacterium adolescentis rpoB mutants conferring resistance to rifampicin, β-lactamases CblA-1, CfxA2, multidrug resistance gene CRP, diaminopyrimidine resistance gene dfrF, fluoroquinolone-resistance gene emrR, macrolide; lincosamide; streptogramin resistance gene ErmB, ErmG, macrolide resistance gene Mef(En2), nucleosidase SAT-4, and tetracycline-resistance genes tet(O), tet(Q), and tet(W). Most of these infants and mothers were not administered any antibiotics. In infants, ARGs were predominantly carried by Bacillota, Pseudomonadota, and Actinomycetota, similar to the mothers. The dominant ARG-carrying opportunistic pathogens were Escherichia coli, Klebsiella, and Streptococcus, found across all infant cohorts. All the core ARGs were associated with mobile genetic elements, signifying the role of horizontal gene transfer(HGT). We detected 132 virulence determinants, mostly E. coli-specific, including pilus chaperones, general secretion pathway proteins, type III secretion system effectors, and heme-binding proteins.

Maternal-neonate transmission of ARGs along with possible nosocomial infections, mode of delivery, breastfeeding versus formula feeding, and gestation period, must be considered for mother-neonate health.

This research aims to explore the effects of incorporating Saccharomyces cerevisiae fermentation products (SCFP) on growth performance, nutrient digestibility, antioxidant capacity, fecal short-chain fatty acids, and microbial composition of pre-weaning calves.

Twenty Holstein calves, 10 days old and weighing an average of 48.63±0.91 kg, were randomly assigned to either the control group (CON) or the SCFP group, with 10 calves in each group. The CON group received only a basal diet, while the SCFP group received the starter diet supplemented with 5 g/head/d of SCFP products. The pre-trial period lasted for 5 days, followed by a main experimental period of 45 days.

The SCFP group had significantly higher final weight, average daily gain, and feed efficiency compared to the CON group (p<0.05). Moreover, the SCFP group exhibited increased apparent digestibility of dry matter, crude protein, ether extract, acid detergent fiber, Ca, and P (p<0.05). Additionally, supplementation with SCFP led to elevated content of growth hormone, insulin-like growth factor-1, and glucagon-like peptide-1 in serum. The inclusion of SCFP also raised serum catalase content and reduced serum malondialdehyde content in pre-weaning calves. Furthermore, SCFP supplementation influenced the composition of intestinal microflora by decreasing Actinobacteriota abundance and increasing the abundance of Ruminococcus, Lachnospiraceae_AC2044_group, Parabacteroides, and Butyricimonas.

The addition of SCFP has a positive impact on the growth performance, nutrient digestibility, antioxidant capacity, and intestinal microflora composition of pre-weaning calves.

Butylated hydroxyanisole (BHA) continues to raise consumer concerns. All previous evaluations of this additive have failed to consider its effect on the gut microbiome, even though it enters the colon. An ex vivo model was used to assess the effect of BHA on microbial communities from 24 donors, aged infants to older adults. A dose of 0.35 g/L BHA elicited no statistically significant changes in the functional outputs or community structure for any age group. Although not large enough to affect community diversity, there were some significant decreases at the phylum level. Among the genes most significantly affected by treatment with BHA across age groups are those involved in lipopolysaccharide synthesis and bacterial electron transport encoded by Bacteroidota, Proteobacteria, and Verrucomicrobiota. Given what is known about the intracellular activity of BHA, these genes may hint at a mechanism behind BHA's evident, but minimally detrimental effect on the gut microbiota.

Gastrointestinal tract of humans provides a niche to thousands of microbes, referred as gut microbiota (GM). GM establishes an intricate relationship with other organs via gut-organ axis, and modulates host health. The structure and functioning of these gut microbes can be influenced by the type of external exposome an individual experiences. Depending upon GM perturbations and host genotype, this can result in variable health implications. On the other hand, the huge arsenal of enzymes possessed by GM can chemically alter the xenobiotic structure. Its consequences can be numerous, including formation of harmful metabolites that cause organ damage, reversal of host detoxification pathways, or favourable health effects. Additionally, GM-mediated bio-transformation of pharmaceuticals can alter their pharmacokinetics and pharmacodynamics, potentially yielding variable drug responses, resulting into prolonged or ineffective treatments. To address this bi-facial relationship and the pivotal role of GM, this review incorporates recent in vitro, in vivo, and multiomics studies. It also suggests the need of machine learning approaches to decode the complex host-microbiota-xenobiotics interactions. These knowledge will aid in comprehending recent rise in chronic lifestyle-diseases which poses a huge burden on the health sector, and can also be a learning curve in making formulations and therapies for personalized treatment.

The increasing global incidence of precocious puberty, linked to environmental, metabolic, and genetic factors, necessitates innovative therapies beyond gonadotropin-releasing hormone (GnRH) analogs. Accumulating evidence implicates gut microbiota dysbiosis as a pivotal regulator of pubertal timing via interactions with hormone metabolism (e.g., estrogen reactivation via β-glucuronidase), neuroendocrine pathways (nitric oxide signaling), and immune-inflammatory responses. This review delineates taxonomic alterations in central precocious puberty (CPP) and obesity-related subtypes, including Streptococcus enrichment and Alistipes depletion, alongside functional shifts in microbial metabolite production. Mechanistic insights highlight microbiota-driven modulation of the hypothalamic-pituitary-gonadal (HPG) axis, leptin/insulin dynamics, and epigenetic regulation. Emerging interventions-probiotics, fecal microbiota transplantation (FMT), and dietary modifications-demonstrate efficacy in preclinical models and early clinical studies for delaying puberty onset and restoring hormonal balance. Translational efforts to validate these strategies are critical for addressing the clinical and psychosocial challenges posed by precocious puberty, positioning gut microbiota modulation as a novel therapeutic frontier in pediatric endocrinology.

To investigate independent effects of group B Streptococcus (GBS) intrapartum antibiotic prophylaxis (IAP) and cesarean delivery (CD) on body mass index (BMI) during early childhood.

Retrospective cohort study of infants (n = 157,820) born 2007-2015 in an integrated healthcare system. Exposures were delivery mode (CD or vaginal delivery [VD]) and GBS IAP exposure. CD was further divided into elective CD (without labor or rupture of membrane [ROM]) or unscheduled CD (following labor and/or ROM). BMI over 5 years was compared using non-linear multivariate models with B-splines, adjusted for demographics, maternal medical and obstetrical factors, and childhood antibiotic exposure.

At age 5 years, unscheduled CD without GBS IAP (Δ BMI 0.11 kg/m2, 95 % CI 0.06 to 0.16, p < 0.0001) and unscheduled CD with GBS IAP (Δ BMI 0.24 kg/m2, 95 % CI 0.11 to 0.36 kg/m2, p = 0.0002) were positively associated with higher BMI compared to their VD counterparts, respectively. No BMI difference was observed between children born by elective versus unscheduled CD. GBS IAP exposure was positively associated with increased BMI compared to non-exposed births in both VD (Δ BMI 0.07 kg/m2, 95 % CI 0.02 to 0.13 kg/m2, p = 0.0125) and CD (Δ BMI 0.22 kg/m2, 95 % CI 0.09 to 0.35 kg/m2, p = 0.0009).

Based on our findings, the widespread administration of GBS IAP and birth by cesarean delivery independently contribute to a significant upshift in body weight early in life that compares to or is higher than the annual increase in BMI in U.S. children on a population level.

Birth cohorts have identified modifiable risk factors for asthma and respiratory health in children and adults, demonstrating the important role and pathways through which early-life events influence not only child outcomes but also adult health, disease, and mortality. This focused literature update from 2021 to 2024 summarizes birth cohort studies across the life-span that contribute to our understanding of risk factors for and the childhood origins of asthma and chronic obstructive pulmonary disease that may inform prevention efforts. We conclude that there are critical periods of developmental plasticity and susceptibility during which early-life events and exposures likely have the greatest impact on the development of asthma and chronic obstructive lung disease phenotypes, and that there are important prenatal and early childhood exposures, which, if modified, might be candidates for improving respiratory health across the life-span. Birth cohorts have been and will continue to be critical to advancing our understanding of lung health and disease across the life-span, including asthma and chronic obstructive pulmonary disease. As child mortality declines and the human population ages, data from birth cohort studies are needed to inform strategies for optimizing healthy longevity, including the investment in understanding the lifelong consequences of adverse prenatal and early childhood exposures.

Microbiome-based dietary supplements have gained attention for their role in enhancing brain development and cognitive health. The gut microbiome influences neurological functions through the gut-brain axis, impacting neurotransmitter production, immune regulation, and metabolic pathways. Dysbiosis is linked to neurological disorders such as Alzheimer's, Parkinson's, and autism spectrum disorders. This chapter explores dietary interventions targeting the microbiome, emphasising probiotics, prebiotics, and postbiotics. Additionally, AI and machine learning are transforming microbiome research by enabling personalised supplementation strategies tailored to individual gut profiles. Ethical challenges, including data privacy and algorithmic bias, are also discussed. Advances in big data analytics and predictive modelling are paving the way for precision-targeted interventions to optimise brain health. While microbiome-based therapies hold great promise, further clinical validation and regulatory frameworks are needed to ensure their efficacy and accessibility. This chapter highlights the future potential of microbiome-targeted strategies in neuroprotection and cognitive well-being.

The current discovery that the gut microbiome, which contains roughly 100 trillion microbes, affects health and disease has catalyzed a boom in multidisciplinary research efforts focused on understanding this relationship. Also, it is commonly demonstrated that the gut and the CNS are closely related in a bidirectional pathway. A balanced gut microbiome is essential for regular brain activities and emotional responses. On the other hand, the CNS regulates the majority of GI physiology. Any disruption in this bidirectional pathway led to a progression of health problems in both directions, neurological and gastrointestinal diseases. In this review, we hope to shed light on the complicated connections of the microbiome-gut-brain axis and the critical roles of gut microbiome in the early development of the brain in order to get a deeper knowledge of microbiome-mediated pathological conditions and management options through rebalancing of gut microbiome.

The development and maintenance of a balanced microbiota is crucial for human health. Milk contains immune factors that not only protect offspring from infectious diseases but also play an important role in promoting the development and maintenance of the microbiota. However, the persisting effects of milk-derived immune factors on the maintenance of the microbiota after weaning have not been carefully examined. In this study, a cross-fostering model was employed using immunocompetent (IC) and immunodeficient (ID) mice in which one-half of the pups born from two dams were replaced. As a result, breast milk from the IC dam (IC milk) affected the development of the microbiota during lactation and maintained it even after weaning in the large intestine of the ID pups. The large intestinal microbiota of ID pups raised on IC milk remained similar to that of normal IC pups. Under normal conditions, the genus Mucispirillum was closely associated with other bacteria, forming a diverse bacterial community in the large intestine. In the small intestine, there were no differences in the microbiota before weaning, regardless of whether IC or ID milk was consumed. By contrast, significant differences were observed in the small intestinal microbiota between IC and ID mice after weaning; however, this was dependent on the immune-related characteristics of offspring (rather than milk-derived immune factors). These results indicate that breast milk plays an important role in the large (not small) intestine of offspring to create and maintain a diverse microbiota with a balanced bacterial network even after weaning.

Bifidobacteria represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest in bifidobacteria as a live biotic therapy, our understanding of colonization, host-microbe interactions, and the health-promoting effects of bifidobacteria is limited. To address these major knowledge gaps, we used a large-scale genetic approach to create a mutant fitness compendium in Bifidobacterium breve. First, we generated a high-density randomly barcoded transposon insertion pool and used it to determine fitness requirements during colonization of germ-free mice and chickens with multiple diets and in response to hundreds of in vitro perturbations. Second, to enable mechanistic investigation, we constructed an ordered collection of insertion strains covering 1,462 genes. We leveraged these tools to reveal community- and diet-specific requirements for colonization and to connect the production of immunomodulatory molecules to growth benefits. These resources will catalyze future investigations of this important beneficial microbe.

Immune health and metabolic functions are intimately connected via diet and the microbiota. Immune cells are continuously exposed to a wide range of microbes and microbial-derived compounds, with important mucosal and systemic ramifications. Microbial fermentation of dietary components in vivo generates thousands of molecules, some of which are integral components of the molecular circuitry that regulates immune and metabolic functions. These in turn protect against aberrant inflammatory or hyper-reactive processes and promote effector immune responses that quickly eliminate pathogens, such as SARS-CoV-2. Potent tolerance mechanisms should ensure that these immune cells do not over-react to non-pathogenic factors (e.g. food proteins), while maintaining the ability to respond to infectious challenges in a robust, effective and well controlled manner. In this review we examine the factors and mechanisms that shape microbiota composition and interactions with the host immune system, their associations with immune mediated disorders and strategies for intervention.

The human gut microbiome within the gastrointestinal tract continuously adapts to variations in diet, medications, and host physiology. A strategy for bacterial genetic adaptation is epigenetic phase variation (ePV) mediated by bacterial DNA methylation, which can regulate gene expression, enhance clonal heterogeneity, and enable a single bacterial strain to exhibit variable phenotypic states. Genome-wide and site-specific ePVs have been characterized in human pathogens' antigenic variation and virulence factor production. However, the role of ePV in facilitating adaptation within the human microbiome remains poorly understood. Here, we comprehensively cataloged genome-wide and site-specific ePV in human infant and adult gut microbiomes. First, using long-read metagenomic sequencing, we detected genome-wide ePV mediated by complex structural variations of DNA methyltransferases, highlighting those associated with antibiotics or fecal microbiota transplantation. Second, we analyzed a collection of public short-read metagenomic sequencing datasets, uncovering a great prevalence of genome-wide ePV in the human gut microbiome. Third, we quantitatively detected site-specific ePVs using single-molecule methylation analysis to identify dynamic variation associated with antibiotic treatment or probiotic engraftment. Finally, we performed an in-depth assessment of an Akkermansia muciniphila isolate from an infant, highlighting that ePVs can regulate gene expression and enhance the bacterial adaptive capacity by employing a bet-hedging strategy to increase tolerance to differing antibiotics. Our findings indicate that epigenetic modifications are a common strategy used by gut bacteria to adapt to the fluctuating environment.

As the population ages, intestinal health in the elderly has become a key area of concern, with gut microbiota dysbiosis emerging as a significant issue. This review summarizes the factors influencing dysbiosis and interventions from both traditional Chinese medicine (TCM) and Western medicine, offering a reference for future research. A comprehensive search of global databases up to March 2024 identified 617 original studies on gut microbiota dysbiosis in individuals aged 65 and older. After applying strict PRISMA guidelines, 20 articles met the inclusion criteria. Key findings are summarized in four areas: 1) the definition and mechanisms of dysbiosis, 2) evaluation tools for gut microbiota imbalance, 3) factors contributing to dysbiosis in the elderly, and 4) pharmacological treatments. Both TCM and Western medicine offer unique advantages in managing gut microbiota dysbiosis, and the choice of intervention should be tailored to the individual's condition. Future research should focus on optimizing integrated TCM and Western medicine approaches to improve outcomes for elderly patients with gut microbiota dysbiosis.

Extraintestinal bacterial infections (EBIs), e.g., urinary tract infection, bacteremia, and meningitis, occur in approximately 10% of febrile infants younger than 60 days. Although many EBI-causing species commonly reside in the infant gut, proof that the digestive system is a pre-infection habitat remains unestablished.

We studied a cohort of febrile term infants < 60 days old who presented to one of thirteen US emergency departments in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Forty EBI cases and 74 febrile controls matched for age, sex, and race without documented EBIs were selected for analysis. Shotgun sequencing was performed of the gut microbiome and of strains cultured from the gut and extraintestinal site(s) of EBI cases, including blood, urine, and/or cerebrospinal fluid. Using a combination of EBI isolate genomics and fecal metagenomics, we detected an intestinal strain presumptively isogenic to the EBI pathogen (> 99.999% average nucleotide identity) in 63% of infants with EBIs. Although there was no difference in gut microbiome diversity between cases and controls, we observed significantly increased Escherichia coli relative abundance in the gut microbiome of infants with EBIs caused by E. coli. Infants with E. coli infections who were colonized by the putatively isogenic pathogen strain had significantly higher E. coli phylogroup B2 abundance in their gut, and their microbiome was more likely to contain virulence factor loci associated with adherence, exotoxin production, and nutritional/metabolic function.

The intestine plausibly serves as a reservoir for EBI pathogens in a subset of febrile term infants, prompting consideration of new opportunities for surveillance and EBI prevention among colonized, pre-symptomatic infants. Video Abstract.

Asthma and allergies have emerged as some of the most common chronic diseases, particularly in developed countries. Epidemiological studies have consistently demonstrated that children growing up in farming/rural environments are less likely to develop these conditions. Over the past three decades, China has experienced unprecedented economic development and urbanisation, accompanied by a rapid rise in the prevalence of allergic disorders. Despite the substantial number of affected individuals, allergy management in China remains inconsistent and often inadequate, compounded by variations in diagnostic criteria and limited healthcare access in less developed regions. Furthermore, the vast population, regional disparities, and methodological inconsistencies in data collection have hindered the acquisition of comprehensive, large-scale epidemiological data. This review examines the factors contributing to asthma and allergies from their early origins, focusing on modifiable factors from a specific perspective of China. Factors related to traditional lifestyle, such as early-life exposure to agricultural farming and poultry, diverse dietary patterns, and early introduction of allergenic foods, appear to offer protection against allergies. Conversely, exposure to open-fire cooking, incense burning, tobacco smoke, as well as early-life antibiotic use and perinatal factors like Caesarean section delivery and prematurity may represent potential risks. A clear understanding of the role of these factors would pave the way for developing effective interventions to mitigate the substantial health and socioeconomic burdens associated with asthma and allergies.

The healthy human infant gut microbiome undergoes stereotypical changes in taxonomic composition between birth and maturation to an adult-like stable state. During this time, extensive communication between microbiota and the host immune system contributes to health status later in life. Although there are many reported associations between microbiota compositional alterations and disease in adults, less is known about how microbiome development is altered in pediatric diseases. One pediatric disease linked to altered gut microbiota composition is cystic fibrosis (CF), a multi-organ genetic disease involving impaired chloride secretion across epithelia and heightened inflammation both in the gut and at other body sites. Here, we use shotgun metagenomics to profile the strain-level composition and developmental dynamics of the infant fecal microbiota from several CF and non-CF longitudinal cohorts spanning from birth to greater than 36 months of life. We identify a set of keystone species that define microbiota development in early life in non-CF infants but are missing or decreased in relative abundance in infants with CF, resulting in a delayed pattern of microbiota maturation, persistent entrenchment in a transitional developmental phase, and subsequent failure to attain an adult-like stable microbiota. Delayed maturation is strongly associated with cumulative antibiotic treatments, and we also detect the increased relative abundance of oral-derived bacteria and higher levels of fungi in infants with CF, features that are associated with decreased gut bacterial density. These findings suggest the potential for future directed therapies targeted at overcoming developmental delays in microbiota maturation for infants with CF.IMPORTANCEThe human gastrointestinal tract harbors a diversity of microbes that colonize upon birth and collectively contribute to host health throughout life. Infants with the disease cystic fibrosis (CF) harbor altered gut microbiota compared to non-CF counterparts, with lower levels of beneficial bacteria. How this altered population is established in infants with CF and how it develops over the first years of life is not well understood. By leveraging multiple large non-CF infant fecal metagenomic data sets and samples from a CF cohort collected prior to highly effective modulator therapy, we define microbiome maturation in infants up to 3 years of age. Our findings identify conserved age-diagnostic species in the non-CF infant microbiome that are diminished in abundance in CF counterparts that instead exhibit an enrichment of oral-derived bacteria and fungi associated with antibiotic exposure. Together, our study builds toward microbiota-targeted therapy to restore healthy microbiota dynamics in infants with CF.

Although cesarean delivery (CD) has been linked to long-term health risks in singleton infants, the impact of delivery mode on long-term health outcomes in preterm twins remains underexplored. A retrospective cohort study was conducted at a tertiary medical center in Israel from 1991 to 2021, comparing preterm twins vaginally delivered (VD) versus cesarean section, excluding cases with congenital malformations or perinatal deaths. Kaplan-Meier survival curves were used to compare the cumulative incidence, and Cox proportional hazards models were applied to adjust for potential confounders. Four thousand twenty-eight preterm twin offspring were included, with 1703 (42%) VD and 2325 (58%) by CD. Preterm twins delivered by CD had a higher incidence of respiratory morbidities (42% vs. 35% in the VD group, p < 0.001), with an adjusted Hazard Ratio (aHR) of 1.15 (95%CI 1.02-1.30). CD was associated with an increased incidence of neurologic morbidities (22% vs. 17% in the VD group, p < 0.001), with an aHR of 1.16 (95%CI 1.02-1.36). CD was associated with a higher incidence of infectious morbidities (69% vs. 62%, p < 0.001), with an aHR of 1.10 (95%CI 1.01-1.21). Gastrointestinal morbidities were more pronounced in the CD group (29% vs. 25%, p < 0.001), but the multivariable analysis did not reach significance (aHR = 1.10, 95%CI 0.95-1.27). Sub-analyses of elective-uncomplicated deliveries showed consistent results for most morbidities.

Cesarean delivery in preterm twins is associated with long-term respiratory, neurologic, infectious and gastrointestinal morbidities of the offspring. The findings suggest the potential benefits of vaginal over cesarean deliveries regarding offspring long-term health complications.

• Studies on singleton births show that cesarean delivery may increase respiratory, infectious, neurological and gastrointestinal outcomes remains inconsistent across term and preterm deliveries. • Cesarean delivery rates remain high despite recommendations to reduce their frequency, yet data on the association between cesarean delivery and morbidity among twins, particularly in small for gestational age twins, is limited.

• This is the first large-scale study demonstrating that cesarean delivery in preterm twins increases the odds of respiratory, neurologic, infectious and gastrointestinal long-term morbidities up to age 18. • The higher rates of respiratory, neurologic, infectious, and gastrointestinal complications persist even in uncomplicated cesarean deliveries.

Antibiotics are a cornerstone of modern medicine, saving countless lives. However, their widespread use presents two major challenges. First, antibiotic-induced changes in the microbiome can disrupt immune function, increasing the susceptibility to diseases associated with these alterations. Second, prolonged antibiotic use fosters the proliferation of antibiotic resistance genes, leading to the emergence of resistant strains and threatening our ability to control infections. These challenges highlight an urgent global health crisis, necessitating in-depth investigation into the multifaceted effects of antibiotic exposure on microbiome dynamics and human health. In this review, we explore the potential effects of antibiotic exposure on the microbiome and its implications for overall health. Additionally, we examine the role of emerging technologies in addressing these challenges and in shaping future antibiotic development. Our goal is to provide insights that will inform more effective public health strategies and interventions aimed at mitigating the adverse consequences of antibiotic use, restoring microbial balance, and improving overall health outcomes.

The gut-brain axis plays a crucial role in the regulation and development of psychological and physical processes. The first year of life is a critical period for the development of the gut microbiome, which parallels important milestones in establishing sleep rhythm and brain development. Growing evidence suggests that the gut microbiome influences sleep, cognition and early neurodevelopment. For term-born and preterm-born infants, difficulties in sleep regulation may have consequences on health. Identifying effective interventions on the gut-brain axis in early life is likely to have long-term implications for the health and development of at-risk infants.

In this multicentre, four-group, double-blinded, placebo (PLC)-controlled randomised trial with a factorial design, 120 preterm-born and 260 term-born infants will be included. The study will investigate whether the administration of daily synbiotics or PLC for a duration of 3 months improves sleep patterns and neurodevelopmental outcomes up to 2 years of age. The trial will also: (1) determine the association between gut microbiota, sleep patterns and health outcomes in children up to 2 years of age; and (2) leverage the interactions between gut microbiota, brain and sleep to develop new intervention strategies for at-risk infants.

The NapBiome trial has received ethical approval by the Committee of Northwestern and Central Switzerland and Canton Vaud, Switzerland (#2024-01681). Outcomes will be disseminated through publication and will be presented at scientific conferences. Metagenomic data will be shared through the European Nucleotide Archive.

The US National Institutes of Health NCT06396689.

Infants exposed to HIV and uninfected (HEUs) are at higher risk of infectious morbidity than HIV-unexposed uninfected infants (HUUs). Multiple immune defects of unknown origin were observed in HEUs. We hypothesized that HEUs have more regulatory and inhibitory checkpoint-expressing T cells (Treg, Tici) than HUUs, which may dampen their immune defenses against pathogens.

We used flow cytometry to measure 25 Treg/Tici subsets in HEUs and HUUs at birth, 6, 28, and 62 weeks of life. We used maternal and infant gut microbiome data reported in a previous study to establish correlations with the Treg/Tici.

At birth, 3 Treg subsets, including the prototypic CD4+FOXP3+ and CD4+FOXP3+CD25+, had higher frequencies in 123 HEUs than in 117 HUUs, and 3 subsets had higher frequencies in HUUs. At 28 and 62 weeks of age, 5 Treg/Tici subsets had higher proportions in HEUs than HUUs. The frequencies of the Treg/Tici subsets that diverged between HEUs and HUUs at birth correlated with differential relative abundances of bacterial taxa in the maternal gut microbiome. The Treg/Tici subsets with significantly different frequencies at subsequent visits correlated with the concurrent composition of the infant gut microbiome. In vitro, treatment of HUU peripheral blood mononuclear cells (PBMC) with bacterial taxa most abundant in HEUs expanded Treg/Tici subsets with higher frequencies in HEUs than HUUs, recapitulating the in vivo correlations. Conversely, in vitro treatment of HEU PBMC did not increase Treg/Tici frequencies. Other factors that correlated with increased Treg/Tici frequencies were low maternal CD4+ T cells in HEUs at birth and male sex in the HUUs at 28 weeks of life.

This study shows that maternal and infant gut dysbiosis are central to the increase in Treg/Tici in HEUs and may be targeted by mitigating interventions.

The world is experiencing a sudden surge in urban population, especially in developing Asian and African countries. Consequently, the global burden of cardio-metabolic disease (CMD) is also rising owing to gut microbiome dysbiosis due to urbanization factors such as mode of birth, breastfeeding, diet, environmental pollutants, and soil exposure. Dysbiotic gut microbiome indicated by altered Firmicutes to Bacteroides ratio and loss of beneficial short-chain fatty acids-producing bacteria such as Prevotella, and Ruminococcus may disrupt host-intestinal homeostasis by altering host immune response, gut barrier integrity, and microbial metabolism through altered T-regulatory cells/T-helper cells balance, activation of pattern recognition receptors and toll-like receptors, decreased mucus production, elevated level of trimethylamine-oxide and primary bile acids. This leads to a pro-inflammatory gut characterized by increased pro-inflammatory cytokines such as tumour necrosis factor-α, interleukin-2, Interferon-ϒ and elevated levels of metabolites or metabolic endotoxemia due to leaky gut formation. These pathophysiological characteristics are associated with an increased risk of cardio-metabolic disease. This review aims to comprehensively elucidate the effect of urbanization on gut microbiome-driven cardio-metabolic disease. Additionally, it discusses targeting the gut microbiome and its associated pathways via strategies such as diet and lifestyle modulation, probiotics, prebiotics intake, etc., for the prevention and treatment of disease which can potentially be integrated into clinical and professional healthcare settings.

The gut microbiota emerged as a potential modulator of brain connectivity in health and disease. This systematic review details current evidence on the gut-brain axis and its influence on brain connectivity. The initial set of studies included 532 papers, updated to January 2024. Studies were selected based on employed techniques. We excluded reviews, studies without connectivity focus, studies on non-human subjects. Forty-nine papers were selected. Employed techniques in healthy subjects included 15 functional magnetic resonance imaging studies (fMRI), 5 diffusion tensor imaging, (DTI) 1 electroencephalography (EEG), 6 structural magnetic resonance imaging, 2 magnetoencephalography, 1 spectroscopy, 2 arterial spin labeling (ASL); in patients 17 fMRI, 6 DTI, 2 EEG, 9 structural MRI, 1 transcranial magnetic stimulation, 1 spectroscopy, 2 R2*MRI. In healthy subjects, the gut microbiota was associated with connectivity of areas implied in cognition, memory, attention and emotions. Among the tested areas, amygdala and temporal cortex showed functional and structural differences based on bacteria abundance, as well as frontal and somatosensory cortices, especially in patients with inflammatory bowel syndrome. Several studies confirmed the connection between microbiota and brain functions in healthy subjects and patients affected by gastrointestinal to renal and psychiatric diseases.

To assess the surgical outcomes of Robot-Assisted Laparoscopic Extravesical Ureteral Reimplantation (RALUR-EV) in infants under one year of age with primary vesicoureteral reflux (VUR) as compared to older children.

A retrospective analysis was conducted on 48 children with VUR who underwent unilateral or bilateral RALUR-EV between June 2018 and December 2022. Patients were divided into two groups: Group A (25 infants under one year) and Group B (23 children over one year). Preoperative evaluations included voiding cystourethrogram (VCUG), diuretic renography, ultrasonography, magnetic resonance urography, and urodynamic studies. Standard follow-up was conducted postoperatively, and both the resolution of reflux and any complications were meticulously documented.

All procedures were completed using the Da Vinci Surgical System without conversion to open surgery or major intraoperative complications. Group A had significantly smaller bladder capacities compared to Group B (70 [60, 90] ml vs. 150 [90, 200] ml, P <0.001) and a higher proportion of refractory febrile UTIs preoperatively (88.00 % vs. 60.87 %, P = 0.030). No significant differences in Operation time, estimated blood loss, or postoperative complications were observed between the groups. The success rates of reflux resolution were 96.00 % in Group A and 95.65 % in Group B. The length of hospital stay was significantly shorter in Group A (5 [4, 6] days vs. 7 [6, 10] days, P = 0.001).

RALUR-EV for the treatment of VUR in infants under one year of age is safe and effective. Compared to older children, the procedure does not increase intraoperative risks, and postoperative outcomes are comparable.

The geriatric population, comprising ages 65 and above, encounters distinct health obstacles because of physiological changes and heightened vulnerability to diseases. New technologies are being investigated to tackle the intricate health requirements of this population. Recent advancements in probiotics and nanotechnology offer promising strategies to enhance geriatric health by improving nutrient absorption, modulating gut microbiota, and delivering targeted therapeutic agents. Probiotics play a crucial role in maintaining gut homeostasis, reducing inflammation, and supporting metabolic functions. However, challenges such as limited viability and efficacy in harsh gastrointestinal conditions hinder their therapeutic potential. Advanced nanotechnology can overcome these constraints by enhancing the efficacy of probiotics through nano-encapsulation, controlled delivery, and improvement of bioavailability. This review explores the synergistic potential of probiotics and advanced nanotechnology in addressing age-related health concerns. It highlights key developments in probiotic formulations, nano-based delivery systems, and their combined impact on gut health, immunity, and neuroprotection. The convergence of probiotics and nanotechnology represents a novel and transformative approach to promoting healthy aging, paving the way for innovative therapeutic interventions.

Food sensitization (FS) develops in early infancy and is a risk factor for subsequent food allergy (FA). Recent evidence suggests relationships of gut microbiota with FS and FA. However, little is known about the role of neonatal gut microbiota in the pathobiology of these manifestations.

We sought to characterize gut microbiota in children using an enterotyping approach and determine the association of gut microbiota and the enterotypes with the development of FS and FA.

We combined gut microbiome and fecal short-chain fatty acid data from 2 longitudinal birth-cohort studies in Japan, clustered the microbiome data from children who were 1 week to 7 years old and their mothers and identified enterotypes. We also determined the associations of gut microbiota and enterotypes with risks of developing FS and FA across the 2 studies using multivariable regression models.

Data from the 2563 microbiomes identified 6 enterotypes. More gut bacteria (eg, Bifidobacterium) in 1-month-old children showed significant relationships with the development of FS and FA than in 1-week-old children. Enterotypes at 1 month old consisted of Bacteroides-dominant, Klebsiella-dominant, and Bifidobacterium-dominant enterotypes. Bifidobacterium-dominant enterotypes with the highest fecal propionate concentration had the lowest risks of developing FS and FA, especially of hen egg white sensitization. Bifidobacterium-dominant enterotypes had lower risks at 2 years old in one study (vs Bacteroides-dominant enterotype, adjusted odds ratio [adjOR]: 0.10, 95% CI: 0.01-0.78; vs Klebsiella-dominant enterotype, adjOR: 0.10, 95% CI: 0.01-0.77) and at 9 months old in the other study (vs Bacteroides-dominant enterotype, adjOR: 0.33, 95% CI: 0.11-0.91).

In these birth-cohort studies, gut microbiome clustering identified distinct neonatal enterotypes with differential risks of developing FS and FA.