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are technical, such as lack of standardized stool collection protocols, inconsistent DNA extraction methods, and outdated sequencing technologies.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.

The initial microbial colonization of the infant gut during birth plays a critical role in shaping both immediate and long-term health outcomes. While mode of delivery is a known determinant of this colonization process, the potential impacts of infant sex and birth order remain underexplored. This study investigates the influence of delivery mode, infant sex, and birth order (maternal parity) on the microbial communities in first-pass meconium samples from neonates, using 16S rRNA gene sequencing. We found that delivery mode impacted the presence of detectable microbial communities. Specifically, only 17% of samples from neonates delivered by elective Cesarean section showed any microbial presence, compared to approximately two-thirds of samples from neonates exposed to maternal vaginal microbes (emergency C-section or vaginal delivery). Among vaginally delivered neonates without antibiotic exposure, birth order was associated with taxonomic shifts. Neonates born to primiparous mothers had a lower abundance of Bifidobacterium, a keystone species in the infant gut microbiome. Unexpectedly, the gut microbiota differed by infant sex, with males having lower alpha diversity and shifts in microbial community composition (PERMANOVA p = 0.008), characterized by elevated levels of Enterobacteriales, which was both less prevalent and less abundant in female neonates. These findings highlight the intricate interplay between delivery mode, infant sex, and birth order in shaping the early gut microbiome.

The factors influencing the establishment of the gut bacterial community in early life are fairly well studied. However, the factors shaping the infant gut virome remain elusive. Interestingly, early life gut virome imbalances have recently been linked with increased risk of developing diseases like type 1 diabetes and asthma. We utilized the deeply phenotyped COPSAC2010 cohort to investigate how environmental factors influence the gut virome at one year age. We demonstrate that the presence of older siblings as well as residential location (urban or rural) had the strongest impact on gut virome composition at 1 year of age. A total of 16,118 species-level clustered viral representative contigs (here termed viral Operational Taxonomic Units - vOTUs) were identified and of these 2105 vOTUs varied in abundance with environmental exposures. Of these vOTUs 94.1% were phages mainly predicted to infect Bacteroidaceae, Prevotellaceae, and Ruminococcaceae. Strong co-abundance of phages and their bacterial hosts was confirmed underlining the predicted phage-host connections. Furthermore, we found some gut viruses affected by environmental factors encode enzymes involved in the utilization and degradation of major dietary components, potentially affecting infant health by influencing the bacterial host metabolic capacity. These findings provide a valuable insights for understanding the early life factors that predispose to autoimmune and metabolic disorders.

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.

Allergic diseases such as asthma, eczema, and food allergies are rising globally. The infant gut microbiota, particularly the dominance of Bifidobacterium, shapes immune development and allergy risk. In Japan-where Bifidobacterium prevalence is notably high-longitudinal investigations focusing on the pre-weaning period, when external influences are relatively limited, remain scarce. Therefore, based on consistent hypotheses and findings from previous studies, we investigated how two important early factors-antibiotic exposure at birth and the presence of older siblings-influence the gut environment in early infancy and subsequent allergy development.

In a prospective cohort of 121 Japanese infants, stool samples were collected at seven time points from birth through 24 months. We quantified the relative abundances of Bifidobacterium, Bacteroides, Clostridium, and Faecalibacterium and recorded allergic outcomes at 2 years. Both antimicrobial exposure at delivery and sibling presence significantly altered gut microbiota composition and overall diversity in early infancy. Although the full cohort showed no consistent diversity or Bifidobacterium differences by allergic status, in several subgroups where these two factors were excluded, infants who had an allergy by 24 months exhibited marked shifts in early gut microbiota community structure-particularly in beta diversity-and reduced Bifidobacterium occupancy during the pre-weaning period (1-6 months) versus non-allergic peers. Moreover, infants whose gut microbiota was initially affected by these factors showed a recovery in diversity after weaning, a rebound more pronounced in non-allergic individuals.

These findings indicate that both the initial community configuration and its capacity to rebound after perturbation are critical determinants of allergy risk. By focusing on dynamic changes through weaning and adjusting for decisive confounders, this study refines insight beyond prior cross-sectional work. Early interventions that preserve or restore microbial diversity and Bifidobacterium dominance may therefore offer a promising strategy to mitigate allergic disease development.

Heart failure is a global health issue with significant mortality and morbidity. There is increasing evidence that alterations in the gastrointestinal microbiome, gut epithelial permeability, and gastrointestinal disorders contribute to heart failure progression through various pathways, including systemic inflammation, metabolic dysregulation, and modulation of cardiac function. Moreover, several medications used to treat heart failure directly impact the microbiome. The relationship between the gastrointestinal tract and the heart is bidirectional, termed the gut-heart axis. It is increasingly understood that diet-derived microbial metabolites are key mechanistic drivers of the gut-heart axis. This includes, for example, trimethylamine N-oxide and short-chain fatty acids. This review discusses current insights into the interplay between heart failure, its associated risk factors, and the gut microbiome, focusing on key metabolic pathways, the role of dietary interventions, and the potential for gut-targeted therapies. Understanding these complex interactions could pave the way for novel strategies to mitigate heart failure progression and improve patient outcomes.

Female fertility and reproductive health depend on a series of developmental steps from embryogenesis through puberty, in addition to the proper functioning of the reproductive system in adulthood. Two important steps are the establishment of the ovarian reserve and development of the hypothalamic-pituitary-ovarian axis. During reproductive years, maintaining an adequate ovarian reserve of follicles as well as balanced neuroendocrine control of reproductive organs is crucial for fertility. Dysregulation of either of these events, during development or in adulthood, can lead to reproductive disorders. Over the past five decades, human fertility rates have declined, whereas the incidence of female reproductive disorders has risen, trends partially linked to environmental factors such as exposure to endocrine-disrupting chemicals (EDCs). Here we outline epidemiological and mechanistic evidence for how EDCs affect the ovarian reserve during early development, its maintenance during adulthood and the establishment of the hypothalamic-pituitary control of puberty and ovulation. Our Review not only reveals strong support for the role of EDC exposure in the development of female reproductive disorders such as abnormal puberty, impaired fertility, premature menopause or polycystic ovarian syndrome, but also highlights knowledge gaps, including the difficulty to prove causality between exposure and human disease manifestation.

Despite the different pathologies and genetic susceptibilities of childhood ALL, T1DM and allergies, these conditions share epidemiological risk factors related to timing of infectious exposures and acquisition of the gut microbiome in infancy. We have assessed whether lower microbiome diversity (Shannon Index) and shared genus/species profiles are associated with pediatric ALL, allergies, and T1DM.

Literature search was performed using PubMed, Embase, Cochrane, and Web of Science databases. Case-control, meta-analyses, and cohort studies were considered for inclusion. Inclusion criteria: (i) subjects age 1-18 years at diagnosis, (ii) reports effect of microbiome measured prior to/at time of diagnosis/first intervention (iii) outcome of ALL, allergies, asthma, or T1DM, (iv) English text. Exclusion criteria: (i) age < 1 or >18 years at diagnosis, (ii) Down Syndrome-associated ALL, (iii) non-English text, (iv) reviews, pre-print, or abstracts, (v) heavily biased studies. Abstract and full text screening were performed by two independent reviewers. Data extraction was performed by one reviewer following PRISMA guidelines. Data were pooled using a random-effects model. Eighty-eight studies were included in the analysis, with seventy-seven in the qualitative analysis and 54 in the meta-analysis. Cases were found to have lower alpha-diversity than controls in ALL (SMD:-0.78, 95%CI:-1.21, -0.34), T1DM (SMD:-1.26, 95%CI:-3.49, 0.96), eczema (SMD:-0.34, 95%CI:-0.56, -0.12), atopy (SMD:-0.06, 95%CI:-0.34, 0.22), asthma (SMD:-0.37, 95%CI:-1.16, 0.42), and food allergy (SMD:-0.11, 95%CI:-0.63, 0.41).

These results highlight similarities in the microbiome diversity and composition of children with ALL, T1DM, and allergies. This is compatible with a common risk factor related to immune priming in infancy and highlights the gut microbiome as a potentially modifiable risk factor and preventative strategy for these childhood diseases.

Historically, multigenerational health and disease transmission have primarily focused on genetic inheritance. However, the discovery that beneficial microorganisms known as commensal microbiota outnumber human genes tenfold has reshaped this perspective, highlighting their critical role in maintaining homeostasis and protecting against pathogens. Unlike the human genome, commensal microbiota is not genetically inherited but is acquired anew with each generation. with initial gut colonization playing a pivotal role in shaping an infant's immune system, neurodevelopment, and long-term health, all heavily influenced by maternal factors. In this review, we examine emerging research on maternal microbial influences on the fetus beginning in utero. We provide an updated overview of the current insights into the impact of the vaginal microbiome during parturition on offspring immunity and discuss the potential long-term health implications for infants born via cesarean section. We explore the advantages and limitations of techniques designed to mitigate these effects, such as vaginal seeding and emphasize that the development of the neonatal immune system is a dynamic process influenced by maternal factors beyond birth, including the transfer of microbiota through breast milk and skin contact. Finally, we present gaps in current research and propose future research directions to deepen our understanding of the impacts of the maternal microbiome on her child. Together, these insights demonstrate how maternal influence on offspring health and immunity extends beyond genetic factors, encompassing the transmission of microbiota, which, in turn, has profound long-term implications for health and disease resilience, offering a novel perspective on intergenerational health dynamics.

Fertility is a dynamic, multifactorial process governed by hormonal, immune, metabolic, and environmental factors. Recent evidence highlights the gut microbiota as a key systemic regulator of reproductive health, with notable impacts on endometrial function, implantation, pregnancy maintenance, and the timing of birth. This review examines the gut-endometrial axis, focusing on how gut microbial communities influence reproductive biology through molecular signaling pathways. We discuss the modulatory roles of microbial-derived metabolites-including short-chain fatty acids, bile acids, and tryptophan catabolites-in shaping immune tolerance, estrogen metabolism, and epithelial integrity at the uterine interface. Emphasis is placed on shared mechanisms such as β-glucuronidase-mediated estrogen recycling, Toll-like receptor (TLR)-driven inflammation, Th17/Treg cell imbalance, and microbial translocation, which collectively implicate dysbiosis in the etiology of gynecological disorders including endometriosis, polycystic ovary syndrome (PCOS), recurrent implantation failure (RIF), preeclampsia (PE), and preterm birth (PTB). Although most current evidence remains correlational, emerging insights from metagenomic and metabolomic profiling, along with microbiota-depletion models and Mendelian randomization studies, underscore the biological significance of gut-reproductive crosstalk. By integrating concepts from microbiology, immunology, and reproductive molecular biology, this review offers a systems-level perspective on host-microbiota interactions in female fertility.

There are significant structural differences between breast milk fat and the fat found in existing infant formulas, and these differences may partly explain the observed variations in growth and development between breastfed and formula-fed infants. This study used mice compared three groups: a control group (mixed vegetable oil), an OPO group (vegetable oil added with OPO), and a human milk fat substitute (HMFS) group formulated to match the fatty acid composition of breast milk. Compared to the control group and OPO group, HMFS-fed mice exhibited reduced body fat content and improved cognitive abilities. Lipidomics studies revealed that these differences in HMFS mice were associated with downregulation of hepatic glycerolipids and upregulation of glycerophospholipids and sphingolipids, facilitating the delivery of long-chain polyunsaturated fatty acids to the brain. Molecular investigations confirmed that HMFS reduces body fat accumulation by inhibiting endogenous fatty acid synthesis and promoting fatty acid β-oxidation, while changes in hepatic lipid profiles result from lipid molecule synthesis and interconversion. Metataxonomic studies demonstrated that HMFS reshaped the gut microbiota, including upregulating Akkermansia and downregulating Desulfovibrio and the Firmicutes/Bacteroidetes ratio, with strong correlations observed between the change of gut microbiota and responded lipids in liver. Overall, the breast milk's unique fatty acid distribution promotes organismal growth by modulating hepatic lipid metabolism, systemic lipid circulation, and gut microbiota. These findings underscore the nutritional benefits of breast milk fat structure and provide insights for the development of next-generation infant formulas.

The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.

1,3-Dioleoyl-2-palmitoyl-glycerol (OPO) is a specific triglyceride in human breast milk, and it has been added to infant formula to mimic human breast milk fat. Existing studies only focused on its effects on fatty acid and calcium absorption, as well as the intestinal microbial composition; however, effects of OPO on the early-life development of intestine were still unclear. Our study explored the effects of OPO on intestinal epithelial structure and barrier construction in neonatal mice and the involvement of intestinal microorganisms. OPO supplementation significantly increased the number of intestinal stem cells, which in turn promoted villus and crypt, and promoted goblet cell and Paneth cell differentiation. OPO also promotes epithelial barrier integrity by increasing the expression of mucin 2, lysozyme 1, and tight junction proteins. Furthermore, the benefits of OPO were associated with the higher abundance of beneficial bacteria (unclassified_f_Muribaculaceae, Akkermansia, Bifidobacterium, and Blautia) and elevated butyrate levels. This study demonstrates the efficacy of OPO on intestinal health in neonatal mice beyond defecation, expands the understanding of the biological functions of OPO, and expands its application in intestinal health products targeting special populations, such as the elderly or individuals with intestinal fragility or injury.

Gestational diabetes mellitus (GDM) increasingly affects women and predisposes both mothers and their infants to short- and long-term health consequences. Emerging research links GDM to maternal gut microbiota dysbiosis. However, the impact of GDM on the infant gut microbiota remains unclear. This cross-sectional study aims to explore potential associations between GDM and the gut microbiota in mothers and their infants, as well as correlations between maternal diet, cardiometabolic profile, and gut microbiota composition.

Gut microbiota taxonomic composition was characterized by 16S rRNA gene sequencing on fecal samples collected at 2 months postpartum from 28 mothers, including 17 with (GDM+) and 11 without (GDM-) GDM, as well as 30 infants, 17 GDM + and 13 GDM-. Variations in overall composition and specific taxa between GDM + and GDM- were assessed. Correlations between maternal cardiometabolic profile, dietary intakes, and taxa were performed.

GDM was associated with the overall composition of gut microbiota between GDM + and GDM- in the maternal group, but not in infants. No statistically significant difference in alpha diversity between groups was found in either mothers or infants. However, 14 taxa showed significantly different abundance between GDM + and GDM- mothers, and 4 taxa differed in infants. Specific taxa at the family rank were correlated with maternal dietary and cardiometabolic variables in both mothers and infants.

GDM exposition was associated with gut microbiota composition in both mothers and infants at two months postpartum. This study enhances our understanding of how maternal health could be linked with the gut microbiota of mothers and their infants.

NCT02872402 (2016-08-04, https://clinicaltrials.gov/study/NCT02872402?term=NCT02872402&rank=1 ) and NCT04263675 (2020-02-07, https://clinicaltrials.gov/study/NCT04263675?term=NCT04263675&rank=1 ).

Preterm birth is a major concern in neonatal care, significantly impacting infant survival and long-term health. The gut microbiome, essential for infant development, often becomes imbalanced in preterm infants, making it crucial to understand the effects of antibiotics on its development. Our study analyzed weekly, 6-month, and 1-year stool samples from 100 preterm infants, correlating clinical data on antibiotic use and feeding patterns. Comparing infants who received no antibiotics with those given empirical post-birth treatment, we observed notable alterations in the gut microbiome's composition and an increase in antibiotic resistance gene abundance early in life. Although these effects diminished over time, their long-term clinical impacts remain unclear. Human milk feeding was associated with beneficial microbiota like Actinobacteriota and reduced antibiotic resistance genes, underscoring its protective role. This highlights the importance of judicious antibiotic use and promoting human milk to foster a healthy gut microbiome in preterm infants.

Background: The human milk microbiome is vital in the formation of the newborn microbiome and affects various health outcomes. Probiotics prevent severe necrotizing enterocolitis in neonates, but uncertainty about their safety is the obstacle to their use. Probiotic organisms and antimicrobial peptides derived from probiotic strains in human milk can offer safer options. Aim: This study is aimed at determining the probiotic properties in the human breastmilk microbiome and their potential antimicrobial activity. Methods: Study Design: We conducted a prospective longitudinal study. Participants: The study included 30 mothers, equally divided among gestational ages of < 32 weeks, 32-36 6/7 weeks, and above 37 weeks at the time of delivery. Milk samples were collected and analyzed at three different time points, that is, colostrum, transition milk (7-9 days), and mature milk (after 14 days). Outcome: The microbiome isolated was tested for probiotic and antimicrobial properties. Results: Three hundred and eighty-one bacterial colonies were isolated, of which 38 different species were identified. Of these, Gemella haemolysans, Micrococcus luteus and lylae, and Staphylococcus hominis and warneri were selected. Few showed bile salt, phenol, and NaCl tolerance, but none showed tolerance to pH. Antimicrobial activity was not seen when isolates or protein extracts were tested against the pathogen. Enhancement in the zone of clearance was seen when a combination of protein and antimicrobial agents was tested compared to antimicrobial alone. The zone of clearance was seen even at one-tenth of the standard concentration of amphotericin B when combined with protein extract. Conclusion: The non-Lactobacillus strains tested showed few probiotic properties. Though the isolates did not exhibit antimicrobial properties, the protein extracted from them enhanced the potency of antimicrobial agents.

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.

Lactational exposure to antibacterial medications may affect the normal development of newborns during this crucial stage and later in adult life. Linezolid (LNZ) is an oxazolidinone antibacterial drug that is effective against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Although it is relatively toxic, there is insufficient data about LNZ use during lactation. This study aimed to elucidate the impact of linezolid administration during lactation on Wistar rats' offspring. Eighteen lactating Wistar female rats were separated into three groups (n = 6): control, therapeutic, and low dose groups. The therapeutic dose group received 61.66 mg/kg of LNZ (equivalent to the human dose), while the low dose group received 15.41 mg/kg of LNZ (1/4 of the human therapeutic dose) by gavage twice daily. All lactating dams and their offspring died four days after receiving a therapeutic dose. In the low dose group, LNZ significantly reduced the body weight of lactating females and their pups. The liver tissue of the pups showed a considerable increase in malondialdehyde levels, along with a decrease in the catalase, glutathione, and superoxide dismutase activities accompanied by moderate histological alterations like congestion, and infiltration, and DNA fragmentation as indicated by comet assay. Microscopic examination of renal tissue revealed glomeruli deterioration, cellular infiltration, and intratubular protein deposits. In conclusion, this study highlights the potential risks linezolid may pose to infants during postpartum. Therefore, there is a need for preweaning monitoring and caution should be taken during breastfeeding.

Short-chain fatty acids (SCFAs), mainly produced by gut microbiota through the fermentation process of dietary fibers and proteins, are crucial to human health, with butyrate, a famous four-carbon SCFA, standing out for its inevitably regulatory impact on both gut and immune functions. Within this narrative review, the vital physiological functions of SCFAs were examined, with emphasis on butyrate's role as an energy source for colonocytes and its ability to enhance the gut barrier while exhibiting anti-inflammatory effects. Knowledge of butyrate synthesis, primarily generated by Firmicutes bacteria, can be influenced by diets with specifically high contents of resistant starches and fiber. Butyrate can inhibit histone deacetylase, modulate gene expression, influence immune functionality, and regulate tight junction integrity, supporting the idea of its role in gut barrier preservation. Butyrate possesses systemic anti-inflammatory properties, particularly, its capacity to reduce pro-inflammatory cytokines and maintain immune homeostasis, highlighting its therapeutic potential in managing dysbiosis and inflammatory diseases. Although butyrate absorption into circulation is typically minimal, its broader health implications are substantial, especially regarding obesity and type 2 diabetes through its influence on metabolic regulation and inflammation. Furthermore, this narrative review thoroughly examines butyrate's growing recognition as a modulator of neurological health via its interaction with the gut-brain axis. Additionally, butyrate's neuroprotective effects are mediated through activation of specific G-protein-coupled receptors, such as FFAR3 and GPR109a, and inhibition of histone deacetylases (HDACs). Research indicates that butyrate can alleviate neurological disorders, including Alzheimer's, Parkinson's, autism spectrum disorder, and Huntington's disease, by reducing neuroinflammation, enhancing neurotransmitter modulation, and improving histone acetylation. This focus will help unlock its full therapeutic potential for metabolic and neurological health, rather than exclusively on its well-known benefits for gut health, as these are often interconnected.

The early life period is increasingly being recognized as a window of opportunity to shape immunity, where microbiota and related probiotics have an important impact. Innate γδ T cells are the first T cells generated in utero, populating epithelial tissues such as the lung and contributing to tissue protection through, for example, IL17 production. Here, we studied the influence of maternal microbiota and probiotic supplementation during pregnancy on innate γδ T cells in the lung and thymus of newborn mice. Detailed time-kinetic experiments showed that at birth, the murine lung T cell population was specifically dominated by IL17-committed γδ T cells expressing an invariant Vγ6Vδ1 TCR. Single-cell RNA-sequencing showed that the biased IL17-commitment of perinatal lung γδT cells is highly conserved between mice and humans. While maternal microbiota depletion with antibiotics tended to decrease the frequency of the lung Vγ6 T cells of the offspring at birth, the maternal administration of Lacticaseibacillus rhamnosus (L.rhm.), but not of Bifidobacterium animalis subsp. lactis (B.lac.), increased significantly their frequency, resulting in the augmentation of the IL17-commitment of the mouse lung T cell compartment. Altogether, our data indicate that the maternal microbiota contributes to the shaping of IL17-committed γδT cells in the lungs of newborns and that maternal administration of specific probiotic strains can enhance this process.

This study analyzed the longitudinal evolution of intestinal microbiota in very preterm neonates (PN) during and after their hospitalization. The bacterial 16S rRNA gene sequencing approach was applied for the analysis of fecal samples (n = 1,307) from 596 PN. Samples were collected at one week after birth, at one month, at the neonatal intensive care unit discharge, and at 3.5 years of age. Over time, the intestinal microbiota of the infants matured progressively, with increasing alpha diversity and decreasing beta diversity. Based on a Dirichlet multinomial mixture clustering approach (DMM), during hospitalization, infants progressed among ten different clusters. At 3.5 years of age, only three clusters were identified. The influence of the gestational age, the neonatal antibiotic administration, and the maternal antibiotic therapy during delivery on the gut microbiota varied over time and depended on the sampling period. Preconceptional maternal body mass index (BMI) was associated with the gut microbiota of infants during the hospitalization period and at 3.5 years of age. Infants with a lower gestational age or those born by Cesarean section shifted between clusters more frequently. Using PICRUSt2, the inferred metabolic pathways revealed a change in the functional capacities of the intestinal microbiota over time. We found that preconceptional maternal BMI was the only consistent perinatal factor influencing the development of the gut microbiota over time. After hospital discharge, infants exhibited a transition toward a microbiota community similar to that of adults by 3.5 years of age, in accordance with the functional metabolic pathways of the gut microbiota.IMPORTANCEThis study is among the very few reports analyzing the gut microbiota development in very preterm infants over time in a large, multicenter population of 596 children from a well-described nationwide birth cohort, with a follow-up until the age of 3.5 years. The maturation of the intestinal microbiota was confirmed to occur over time, with increased alpha diversity and decreased beta diversity. Specifically, 13 microbiota clusters were identified during the hospitalization period, while and only three clusters were observed at 3.5 years. Infants born prematurely or via Cesarean section exhibited a less stable microbiota, frequently shifting clusters. A number of perinatal factors were identified as influencing the development of the microbiota. Among these, the preconceptional maternal BMI emerged as the only consistent factor up to 3.5 years. The metabolic pathways of the microbiota evolved over time, in accordance with the maturation of the gut microbiota.

Background: Oral thrush is a common yeast infection caused by Candida albicans in infants during their first few weeks or months. Infant mothers' antibiotics consumption can contribute to this opportunistic fungal growth due to their weaker immune systems. Objectives: To investigate the relationship between maternal antibiotic consumption and oral thrush infection in breastfeeding infants, this study aims to provide insights for health care professionals regarding antibiotic prescriptions and preventive strategies for managing oral thrush. Methods: A quasi-experimental design with a control group was used. Eighty-two breastfeeding infants were divided into two groups: Group 1 (n = 40) infants of antibiotic-consuming mothers and Group 2 (n = 42) infants of nonantibiotic-consuming mothers. The oral samples were collected using sterile cotton swabs and cultured on Sabouraud's dextrose agar C. albicans, confirmed by simple staining and a germ tube test. Results: Infants aged 1-11 months with a mean ± standard deviation of 4.8 ± 3.51. Within all 82 oral swabs, 42.7% were positive for C. albicans growth and 57.3% were negative. The highest percentage was in 1-month-old infants (n = 9, 25.71%), and the lowest was in 11 months old (n = 2, 5.71%). Group 2 infants had significantly fewer positive C. albicans growth (n = 12, 28.57%) compared with group 1 (n = 23; 57.5%) (χ2 = 7.0, p = 0.007; odds ratio = 3.332, 95% confidence interval = 1.35-8.46). Oral thrush clinical signs were identified in 66.6% and 33.4% of group 1 and 2 infants, respectively, while 31.4% of C. albicans-positive colonization showed no clinical manifestations. Conclusion: Maternal antibiotic consumption for more than 1 week is associated with the occurrence of oral thrush in breastfeeding infants. Differences in clinical signs in two groups of infants indicate the importance of laboratory tests for early oral thrush diagnosis. This can help health care professionals understand oral thrush causes, enable early detection, improve treatment, and enhance appropriate antibiotic use in breastfeeding mothers.

As humans, we host personal microbiomes intricately connected to our biology and health. Far from being isolated entities, our microbiomes are dynamically shaped by microbial exchange with the surroundings, in lifelong microbiome acquisition and transmission processes. In this Review, we explore recent studies on how our microbiomes are transmitted, beginning at birth and during interactions with other humans and the environment. We also describe the key methodological aspects of transmission inference, based on the uniqueness of the building blocks of the microbiome - single microbial strains. A better understanding of human microbiome transmission will have implications for studies of microbial host regulation, of microbiome-associated diseases, and for effective microbiome-targeting strategies. Besides exchanging strains with other humans, there is also preliminary evidence we acquire microorganisms from animals and food, and thus a complete understanding of microbiome acquisition and transmission can only be attained by adopting a One Health perspective.

Maternal high fat diet (MHFD) increased colitis susceptibility in adulthood. However, the mechanism remains unclear. We sought to explore whether novel gut immune receptor leucine-rich repeat C19 (LRRC19) contributed to the impaired mucus barrier of offspring exposed to MHFD via gut immune response and microbiota. The results showed that MHFD significantly impaired the intestinal mucus barrier of offspring, and up-regulated the expression of LRRC19. Lrrc19 deletion alleviated the mucus barrier disruption. Mechanistically, metagenome sequencing revealed that the MHFD-induced gut microbiota alteration was partly restored in Lrrc19-/- offspring. Muc2-associated bacteria were decreased in the MHFD group, such as Akkermansia_muciniphila_CAG_154, which increased in the Lrrc19-deficient offspring. Moreover, Lrrc19-/- offspring had a higher rate of indole-3-acetic acid (IAA)-producing bacterium, such as Lactobacillus reuteri. A targeted metabolomics analysis revealed that IAA emerged as the top candidate that might mediate the protective effects. IAA was found to improve the mucus barrier function by increasing the ratio of interleukin-22 (IL-22)+ ILC3 cells in an aryl hydrocarbon receptor (AhR)-dependent manner. These results suggest that MHFD disrupts the intestinal mucus barrier of offspring through regulating gut immune receptor LRRC19 and inducing an imbalance of gut microbiota and microbiota-derived metabolites.

Necrotizing enterocolitis (NEC) is a common pediatric emergency primarily afflicting preterm infants, yet its mechanisms remain to be fully understood. Here, we report that plasma fibroblast growth factor (FGF)19, a target of farnesoid X receptor (FXR), was positively correlated with the clinical parameters of NEC. NEC patients and the NEC murine model displayed abundant FXR in intestinal epithelial cells (IECs), which was restricted by microbiota-derived short-chain fatty acids (SCFAs) under homeostasis. Genetic deficiency of FXR in IECs caused remission of NEC. Mechanistically, FXR facilitated ferroptosis of IECs via targeting acyl-coenzyme A synthetase long-chain family member 4 (Acsl4). Lipid peroxides released by ferroptotic IECs suppressed interleukin (IL)-22 secretion from type 3 innate lymphoid cells (ILC3s), thereby exacerbating NEC. Intestinal FXR antagonist, ACSL4 inhibitor, and ferroptosis inhibitor ameliorated murine NEC. Furthermore, the elevated lipid peroxides in NEC patients were positively correlated with FGF19 and disease parameters. These observations demonstrate the therapeutic value of targeting intestinal FXR and ferroptosis in NEC treatment.

Diarrhea is a common complication in patients after cholecystectomy. In China, tens of millions of patients experience diarrhea every year after cholecystectomy, which results in long-term pain in patients. Traditional Chinese medicine is a national treasure and has made great contributions to human health throughout the long history of the Chinese nation. However, as a classic ready-for-use traditional Chinese medicine, the exact clinical efficacy of the Xianglian preparation needs further observation. This article presents the protocol of a single-center, randomized controlled trial to evaluate the clinical efficacy of Xianglian capsules in patients with diarrhea after cholecystectomy.

This study was conducted in the Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital of Guangdong Medical University, following the recommendations of the current SPIRIT and CONSORT statements. We will recruit 90 patients who have developed diarrhea after cholecystectomy and randomize them 1:1 into the observation and control groups. The control group was given starch placebo capsules, and the observation group was given Xianglian capsules. Patient diarrhea-related indicators were collected at baseline and 5 days postdose. We will also collect patients' intestinal inflammation-related indicators and fecal microbial samples to analyze the possible mechanism of action of drugs.

This study will clarify the clinical effects of the Xianglian preparation on patients with diarrhea after cholecystectomy, provide evidence-based evidence, and promote the development and application of this classic prescription.

http://www.chictr.org.cn .

ChiCTR2200061854. Registered on 04 July 2022.

Neonates primarily rely on innate immune defense, yet their inflammatory responses are usually restricted compared to adults. This is controversially interpreted as a sign of immaturity or essential programming, increasing or decreasing the risk of sepsis, respectively. Here, combined transcriptomic, metabolic, and immunological studies in monocytes of healthy individuals reveal an inverse ontogenetic shift in metabolic pathway activities with increasing age. Neonatal monocytes are characterized by enhanced oxidative phosphorylation supporting ongoing myeloid differentiation. This phenotype is gradually replaced during early childhood by increasing glycolytic activity fueling the inflammatory responsiveness. Microbial stimulation shifts neonatal monocytes to an adult-like metabolism, whereas ketogenic diet in adults mimicking neonatal ketosis cannot revive a neonate-like metabolism. Our findings disclose hallmarks of innate immunometabolism during healthy postnatal immune adaptation and suggest that premature activation of glycolysis in neonates might increase their risk of sepsis by impairing myeloid differentiation and promoting hyperinflammation.

Amoxicillin is a widely used antibiotic globally, and its pervasive environmental presence poses significant risks to human health and ecosystems. Notably, prenatal amoxicillin exposure (PAmE) may have long-term neurodevelopmental toxicity for offspring. In this study, we investigated the lasting effects of PAmE on depressive-like behaviors in offspring rats, emphasizing the biological mechanisms mediated by changes in gut microbiota and its metabolite, myristic acid. Our results showed that PAmE significantly disrupted the gut microbiota composition in offspring, particularly through the reduction of Lachnospiraceae, leading to decreased levels of myristic acid. This disruption hindered the N-myristoylation of ADP-ribosylation factor 1 (ARF1), impaired the normal degradation of the stimulator of interferon genes protein, inhibited autophagic processes, and promoted M1 polarization of microglia, ultimately leading to depressive-like behaviors in the offspring. Remarkably, supplementation with Lachnospira or myristic acid effectively reversed the PAmE-induced neurodevelopmental and behavioral abnormalities, alleviating depressive-like symptoms. This study reveals how PAmE affects offspring neurodevelopment and behavior through gut microbiota and myristic acid, highlighting the crucial role of the gut-brain axis in the modulation of depressive symptoms. Supplementing Lachnospira or myristic acid could represent a novel strategy to mitigate PAmE-induced fetal-originated depression, providing new biological evidence and potential therapeutic avenues.

With the help of rumen bacteria, ruminants can feed on indigestible plant materials and produce over 70% of their energy as fatty acids. However, during lactation, ruminants exhibit characteristics of monogastric animals due to an undeveloped rumen; therefore, understanding gut microbiome changes in growing calves is essential. Our understanding of the gut microbiome in growing calves remains limited in large populations with the same diet, breed, and period. Here, we describe 16S rRNA gene amplicon sequencing data from 420 faecal samples, 20 rumen contents, 17 small intestine contents, and 18 large intestine contents collected from 57 healthy, antibiotic-free Korean beef cattle from neonatal to post-pubertal age. Eight 16S rRNA gene amplicon datasets from the host diet samples were obtained. Approximately 148 million raw reads, averaging 153,352 ± 96,050 (mean ± SD) reads per sample, and 51,596 unique amplicon sequence variants (381-368 per sample) were identified in the 483 samples. These shareable datasets can be reused by researchers to assess gut microbiome-related functions in growing calves and improve ruminant production and health.

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.

In early-life, the gut microbiota is highly modifiable, being modulated by external factors such as maternal microbiota, mode of delivery, and feeding strategies. The composition of the child's gut microbiota will deeply impact the development and maturation of its immune system, with consequences for future health. As one of the main sources of microorganisms to the child, the mother represents a crucial factor in the establishment of early-life microbiota, impacting the infant's wellbeing. Recent studies have proposed that dysbiotic maternal gut microbiota could be transmitted to the offspring, influencing the development of its immunity, and leading to the development of diseases such as obesity. This paper aims to review recent findings in gut microbiota and immune system interaction in early-life, highlighting the benefits of a balanced gut microbiota in the regulation of the immune system.

The gut microbiota plays a pivotal role in influencing the metabolism and immune responses of the body. A balanced microbial composition promotes metabolic health through various mechanisms, including the production of beneficial metabolites, which help regulate inflammation and support immune functions. In contrast, imbalance in the gut microbiota, known as dysbiosis, can disrupt metabolic processes and increase the risk of developing diseases, such as obesity, type 2 diabetes, and inflammatory disorders. The composition of the gut microbiota is dynamic and can be influenced by environmental factors such as diet, medication, and the consumption of live bacteria. Since the early 1900s, bacteria isolated from food and have been used as probiotics. However, the human gut also offers an enormous reservoir of bacterial strains, and recent advances in microbiota research have led to the discovery of strains with probiotic potentials. These strains, derived from a broad spectrum of microbial taxa, differ in their ecological properties and how they interact with their hosts. For most probiotics bacterial structural components and metabolites, such as short-chain fatty acids, contribute to the maintenance of metabolic and immunological homeostasis by regulating inflammation and reinforcing gut barrier integrity. Metabolites produced by probiotic strains can also be used for bacterial cross-feeding to promote a balanced microbiota. Despite the challenges related to safety, stability, and strain-specific properties, several newly identified strains offer great potential for personalized probiotic interventions, allowing for targeted health strategies.

IgE-mediated food allergy (FA) is a major global health concern. Although the early introduction of allergenic foods and breastfeeding are potential preventive strategies, the role of breast milk in reducing the incidence of FAs remains inconclusive.

To investigate the impact of exclusive breastfeeding for the first 4 months compared with partial breastfeeding or cow's milk formula (CMF) on the development of IgE-mediated FAs in an Israeli cohort.

A cross-sectional online survey in 3030 mothers with infants aged 6 to 24 months collected data on early feeding practices, allergen introduction, atopic conditions, and family history. It documented suspected allergic reactions, symptoms, and diagnostic procedures.

Of the 3030 mothers surveyed, 2920 provided complete feeding data for the first 4 months. Among them, 39.0% exclusively breastfed, 12.1% used CMF, and 48.9% partially breastfed. There were 392 infants with FAs, totaling 480 cases involving cow's milk, sesame, egg, or peanut. Of these cases, 122 (25.4%) were in the breastfeeding group, and 358 (74.6%) were in the other groups. Exclusively breastfed infants had lower odds of egg (odds ratio [OR] = 0.53), sesame (OR = 0.58), and peanut (OR = 0.53) allergies than others. The interaction between feeding patterns and atopic dermatitis (AD) related to these FAs was not significant. Exposure to CMF in the nursery, exclusively breastfed, was associated with higher odds of developing a cow's milk allergy. Delayed exposure to sesame in infants with AD has been linked to increased odds of developing a sesame allergy.

Exclusive breastfeeding may reduce the risk of IgE-mediated FA development, regardless of AD status.

To investigate the effect of early childhood infections and antibiotic use on the risk of type 1 diabetes in a general population cohort.

The All Babies In Southeast Sweden (ABIS) cohort followed 16 428 children from birth. Questionnaires collected at 1 year (n=11 093), 3 years (n=8 890) and 5 years of age (n=7 445) included data on infections and antibiotic use and were validated against national registers. After a mean follow-up of 25 years, 168 individuals have been diagnosed with type 1 diabetes (1.0% of the original cohort, aged 1-24.5 years).

There were few significant differences in type or frequency of early childhood infections or antibiotic use between cases with type 1 diabetes and the reference group (remaining individuals who did not develop type 1 diabetes) after adjusting for sex, heredity and socioeconomic status. A small number of type 1 diabetes children (4.8% compared to 0.8% of the reference group) reported six or more episodes of gastroenteritis in the 1-3-year age group, resulting in an adjusted odds ratio (aOR) of 8.21; 95% CI 2.70-25.01, p<0.001. Cases of type 1 diabetes with an increased genetic risk (n=91) reported fewer episodes of the common cold between 1 and 3 years of age compared to the reference group (aOR 0.27; 0.13-0.58, p<0.001). Individuals with type 1 diabetes without risk-associated HLA alleles (n=14) reported a higher frequency of pneumonia in the 1-3- and 3-5-year age group (aOR 26.08; 6.29-108.17, p<0.001 and aOR 35.63; 4.10-309.96, p=0.001 respectively), and had more viral and total infections registered in the National Patient Register from 0-5 years (aOR 5.72; 1.59-20.57, p=0.008 and aOR 18.71; 1.95-179.55, p=0.01).

Childhood infections could increase the risk of developing type 1 diabetes in a small group of individuals without risk-associated HLA alleles, but this was not seen in the majority with HLA-risk. More research is required for this overlooked population, including screening and prevention trials. The association to frequent gastrointestinal infections in the first years of life needs to be reproduced in other studies to be confirmed.

Antibiotic-induced disruption of the gut microbiome in the first 1000 days of life is linked to an increased risk of the development of immunological, metabolic, and neurobehavioral childhood-onset conditions. Supporting the recovery of the gut microbial community after it has been perturbed by antibiotics might be a promising strategy to reduce these risks. In this clinical study, the effect of a 6 weeks supplementation with synbiotics (Bifidobacterium breve M-16 V, short chain galacto-oligosaccharides and long chain fructo-oligosaccharides) after antibiotic treatment on the recovery speed of the gut microbiota of toddlers will be studied.

A cohort of 126 Dutch toddlers aged 12 to 36 months old, who receive an amoxicillin or amoxicillin/clavulanic acid treatment, will be followed for 12 weeks. Participants will be randomized into an intervention group, who will consume the study product over a 6 weeks period starting at the last day of the antibiotic treatment or into a control group that will continue their usual eating pattern. Stool samples and their characteristics will be collected weekly by both groups. Stool samples will be analyzed for total microbiota and Bifidobacterium spp.. The differences in the proportion of Bifidobacterium out of total gut microbiota, composition of species belonging to Bifidobacterium, and beta diversity overtime will be compared between the two groups to study the effect of the intervention on the gut microbiota after perturbation. Furthermore, the effect of the treatment will also be studied in terms of the gut microbiota metabolic activity and stool characteristics. Additionally, food intake will be recorded to investigate whether diet, especially dietary fibers, may influence the gut microbiota as well. The findings may highlight a potential intervention strategy to support the recovery of the gut community after it has been perturbed by antibiotics in early life.

The TOBBI trial was approved by the board of Medical Ethics Review Committee NedMec in June 2022 and registered at  https://www.onderzoekmetmensen.nl/en/trial/20358 under the code NL75975.081.20, and at the World Health Organization at https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON20358 under NTR-new: NL8996.