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are technical, such as lack of standardized stool collection protocols, inconsistent DNA extraction methods, and outdated sequencing technologies.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

Diet is one of the main factors shaping the human microbiome, yet our understanding of how specific dietary components influence microbial consortia assembly and subsequent stability in response to press disturbances - such as increasing resource availability (feeding rate) - is still incomplete. This study explores the reproducible re-assembly, metabolic interplay, and compositional stability within microbial consortia derived from pooled stool samples of three healthy infants. Using a single-step packed-bed reactor (PBR) system, we assessed the reassembly and metabolic output of consortia exposed to lactose, glucose, galacto-oligosaccharides (GOS), and humanized GOS (hGOS). Our findings reveal that complex carbohydrates, especially those containing low inclusion (~1.25 gL-1) components present in human milk, such as N-acetyl-lactosamine (LacNAc), promote taxonomic, and metabolic stability under varying feeding rates, as shown by diversity metrics and network analysis. Targeted metabolomics highlighted distinct metabolic responses to different carbohydrates: GOS was linked to increased lactate, lactose to propionate, sucrose to butyrate, and CO2, and the introduction of bile salts with GOS or hGOS resulted in butyrate reduction and increased hydrogen production. This study validates the use of single-step PBRs for reliably studying microbial consortium stability and functionality in response to nutritional press disturbances, offering insights into the dietary modulation of microbial consortia and their ecological dynamics.

Gestational diabetes mellitus (GDM) is known to be associated with dysbiosis of offspring gut microbiota, but the mechanism remains unclear. The present prospective study explored the role of human milk fatty acid composition in this association. Mothers with GDM and normal controls were recruited at 24-28 gestational weeks. Follow-up was conducted at 1-3 days postpartum and 1 month postpartum to collect human milk and infant feces. A total of 80 mother-infant pairs (40 in the GDM group and 40 in the normal group) were included in the study. The mothers received guidance on diet and exercise but not drug therapy. All infants were exclusively breastfed. We observed significant differences in 8 phyla and 13 genera in the infant between GDM and normal groups at 1-3 days postpartum or 1 month postpartum. Among these bacteria, significant time × group interaction was observed for 7 phyla (such as Acidobacteriota, Gemmatimonadota, and Myxococcota) and 9 genera (such as Sphingomonas, Allorhizobium Neorhizobium Pararhizobium Rhizobium, and TM7a), after adjusting for confounding factors. Changes in these differential infant bacteria were negatively correlated with changes in C18:3n-3 and total n-3 PUFA levels of breast milk. The increases in C18:3n-3 and total n-3 PUFA levels in human milk over time were much greater in the normal group compared to the GDM group. Our findings indicate that altered human milk fatty acid composition is one important reason for GDM-related dysbiosis of offspring gut microbiota.

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.

Necrotizing Enterocolitis (NEC) is a severe, life-threatening inflammatory condition of the gastrointestinal tract, especially affecting preterm infants. This review consolidates evidence from various biomedical disciplines to elucidate the complex pathogenesis of NEC, integrating insights from clinical, microbial, and molecular perspectives. It emphasizes the modulation of NEC-associated inflammatory pathways by probiotics and novel biologics, highlighting their therapeutic potential. We further critically examine dysbiotic alterations within the gut microbiota, with a particular focus on imbalances in bacterial and viral communities, which may contribute to the onset of NEC. The intricate interactions among toll-like receptor 4 (TLR4), microvascular integrity, immune activation, and the inflammatory milieu are meticulously summarized, offering a sophisticated understanding of NEC pathophysiology. This academic review aims to enhance the etiological comprehension of NEC, promote the development of targeted therapeutic interventions, and impart the significant impact of perinatal factors on the formulation of preventive and curative strategies for the disease.

The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in sewage is well-established, but the concomitant changes in microbial compositions during the pandemic remain insufficiently explored. This study investigates the impact of the SARS-CoV-2 virus on microbial compositions in raw sewage, utilizing high-throughput 16S rRNA amplicon sequencing to analyze wastewater samples collected from six dormitories over a one-year field trial at the University of Tennessee, Knoxville. The concentration of SARS-CoV-2 RNA was assessed using a reverse transcription-quantitative polymerase chain reaction. Significant variations in bacterial composition were evident across the six dormitories, highlighting the importance of independently considering spatial differences when evaluating the raw wastewater microbiome. Positive samples for SARS-CoV-2 exhibited a prominent representation of exclusive species across all dormitories, coupled with significantly reduced bacterial diversity compared to negative samples. The correlation observed between the relative abundance of enteric pathogens and potential pathogens at sampling sites introduces a significant dimension to our understanding of COVID-19, especially the notable correlation observed in positive SARS-CoV-2 samples. Furthermore, the significant correlation in the relative abundance of potential pathogens between positive and negative SARS-CoV-2 raw sewage samples may be linked to the enduring effects of microbial dysbiosis observed during COVID-19 recovery. These findings provide valuable insights into the microbial dynamics in raw sewage during the COVID-19 pandemic.

In experimental models, the prenatal diet influences gut microbiota composition in mothers and offspring; however, it is unclear whether this occurs in humans. We investigated the effects of a gut-focused perinatal dietary intervention on maternal and infant gut microbiota composition four weeks after birth.

This randomised controlled trial randomised pregnant women to receive dietary advice as part of standard care, or additionally receive a dietary intervention focused on the Australian Dietary Guidelines and increasing prebiotic and probiotic/fermented food intakes (ACTRN12616000936426). Study assessments occurred from gestation week 26 (baseline) to four weeks postpartum (follow-up). Faecal samples, collected at baseline for mothers, and follow-up for mothers and infants, underwent 16SrRNA sequencing. The primary outcome was a between-group mean difference in infant faecal Shannon index. Secondary outcomes included between-group differences in other microbiota measures, including maternal change from baseline CLR-transformed Prevotella abundance.

Forty-four women and 45 infants completed the study. The mean Shannon index of infants in the intervention group was -0.35 (95% CI: -0.64, -0.06, SD: 0.52) units lower than control group infants, corresponding to a medium effect size (Cohen's D: -0.74, 95% CI: -1.34, -0.13). The findings were similar using other metrics of α-diversity. There were no between-group differences in β-diversity, nor any differentially abundant taxa in infants. The intervention increased abundances of the genus Prevotella in mothers compared to controls.

This gut-focused perinatal dietary intervention was associated with differences in the maternal and infant gut microbiota composition. Larger studies are required to replicate and extend these findings.

In the early days, maternal immunoglobulins are essential for sustaining a balanced gut environment by influencing the interaction between the host and the microbiome. The successional establishment of the pioneer strains is an interesting topic of research where maternal immunoglobulins appear to be important. This proof-of-concept study explored the binding pattern of IgA1, IgA2, IgM, and IgG classes to a commensal bacterial in human colostrum and the stool of breastfed neonates. We used flow cytometry coupled with 16S rRNA gene sequencing in human colostrum and neonatal feces samples to characterize this Ig-microbiota association. We observed that in human colostrum samples, IgA2 and IgM bind alfa and beta Proteobacteria, which can potentially stimulate neonatal immune system development in the gut. Other immunoglobulins like IgG predominantly bind facultative anaerobes belonging to the Firmicutes phylum, reported as part of human milk microbiota and pioneer colonizers of the neonatal gut. Maternal immunoglobulins also bind a wide diversity of bacteria in the neonatal stool. For instance, IgA2 and IgM bound more members of the phylum Bacteroidetes in comparison to IgG, these Bacteroidetes and some firmicutes have been reported as late colonizers of the neonatal gut, and their presence is important due to their ability to produce important short chain fatty acids like propionate and butyrate. Our results support the current view that microbial and immunoglobulin transference is crucial for developing the neonate's immune system and individual gut microbiota.

The suckling period in pigs is a key phase in development for shaping the gut microbiota, which is essential for maintaining biological homeostasis in neonates. In piglets fed sow milk, the gut microbiota comprises predominantly lactobacilli, indicating a host-gut microbiota symbiosis that is influenced by sow milk components. In this study, we sought to elucidate the mechanisms underlying the establishment and maintenance of the gut microbiome in suckling piglets, with a specific focus on the metabolism of sialyl-oligosaccharides by lactobacilli.

Based on liquid chromatography-mass spectrometry analysis, we identified 3'-sialyl-lactose (3'SL) as the major oligosaccharide in porcine milk, and microbiome profiling revealed the predominance of Ligilactobacillus salivarius during the suckling period, with a subsequent transition to Limosilactobacillus reuteri dominance post-weaning. Notably, sialic acid metabolism was established to be exclusively attributable to L. salivarius, thereby highlighting the pivotal role of 3'SL in determining species-specific bacterial segregation. L. salivarius was found to metabolize 3'SL when co-cultured with Bacteroides thetaiotaomicron, resulting in a shift in the predominant short-chain fatty acid produced, from lactate to acetate. This metabolic shift, in turn, inhibits the growth of enterotoxigenic Escherichia coli. Furthermore, the comparison of the gut microbiota between suckling piglets and those fed a low-3'SL formula revealed distinct diversity profiles. We accordingly speculate that an absence of sialyl-oligosaccharides in the formula-fed piglets may have restricted the growth of sialic acid-utilizing bacteria such as L. salivarius, thereby leading to a higher abundance of Enterobacteriaceae.

Our findings reveal the influence of sialyl-oligosaccharides in promoting microbial diversity and gut homeostasis, thereby highlighting the importance of sialic acid as a key factor in shaping milk-driven microbial colonization during the early stages of piglet development. Video Abstract.

Watery Mouth Disease is the main disease in neonatal lambs, causing great economic losses. Despite this, the cause of the condition remains poorly understood. Therefore, we have analysed the main bacteria found in sick animals, their intestinal and temporal distribution, as well as the main sources of contamination. Twelve different farms were sampled, from which 331 samples were taken in total. From these samples, 184 environments were analyzed using 16S rRNA amplicon sequencing, 164 isolates were identified by whole genome sequencing and 35 bacterial counts were performed. The dominant bacterial groups at the rectal level were Escherichia-Shigella (36 %) and Clostridium (29 %), with a homogeneous distribution along the digestive tract and a maximum abundance ranging between 12 and 24 hours of lamb life. Within Escherichia-Shigella: Escherichia coli and Escherichia fergusonii and within Clostridium: Clostridium perfringens, Clostridium cadaveris, Clostridium tertium and Clostridium paraputricum were identified as the main isolates present in sick animals. The high presence of Clostridium strains, especially potentially pathogenic species like C. perfringens in sick animals, point out Clostridium as a new important protagonist of watery mouth disease and the need of their inclusion in future studies. In particular, bedding was established as the main microbial contaminating factor, reaching the highest increase 48 hours after removal and cleaning of the lambing area (i.e. 8.03 ×108, 1.88 ×106, 3.88 ×106, 4.85 ×107 and 4.00 ×105 CFU/g for mesophilic aerobes, coliforms, E. coli, mesophilic anaerobes and sporulates, respectively). These results highlight the need to increase cleanliness in bedding to reduce the presence of these bacteria.

Colonic permeability is a major consequence of dysbiosis and diseases affecting the colon, further contributing to inflammation and extraintestinal diseases. Recent advances have shed light on the association between colonocyte energy utilization and the mechanisms that support epithelial function and homeostasis. One unifying theme is the induction of colonocyte hypoxia, driven by the aerobic oxidation of microbial-derived butyrate, as a critical factor promoting multiple cellular processes that support intestinal barrier function, mucus secretion, and the maintenance of synergistic luminal microbes. Particular attention will be focused on experimental evidence supporting beta-oxidation via activation of peroxisome proliferators-activated receptor-γ (PPAR) and upregulation and activation of processes that promote barrier function by hypoxia-inducible factor (HIF) signaling. Growing evidence suggests that colonocyte energy utilization is tightly regulated and switches between beta-oxidation of butyrate and anaerobic glycolysis, the latter being associated with several disease states. As most of the primary literature associated with colonocyte energy utilization has focused on adult models, evidence supporting butyrate oxidation in the neonatal gut is lacking. Thus, this review details the current state of knowledge linking colonocyte substrate utilization to mechanisms supporting gut health, but also highlights the counterindications of colonic butyrate availability and utilization in developmental periods.

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.

Until recently, it was believed that bacterial translocation occurs as a result of leaky gut syndrome or sepsis. To confirm or exclude the process of bacterial translocation, biomarkers can be used. One such biomarker is defensins, which indicate immune activity, as defensins are cationic peptides with antibacterial properties produced by intestinal epithelial cells. Also, fatty acid-binding proteins (I-FABP and L-FABP) can serve as useful serological markers for intestinal epithelial damage, indicating impaired intestinal permeability or organ damage, as high concentrations of them are found in tissues and low concentrations in blood serum. In the context of obesity, the integrity of the intestinal barrier, which can be disrupted by dietary fat, leads to increased intestinal permeability. Since bacterial translocation and microbiota contribute to obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) associated with metabolic dysfunction, intestinal barrier markers can be used to study the role of the gut-liver axis. The aim of this study was to gain insight into the pathogenesis of MASLD and examine the impact of bacterial translocation markers and intestinal and hepatic fatty acid-binding proteins (I-FABP and L-FABP) in children with MASLD. Method: We examined 60 children with MASLD and overweight/obesity (MASLD was diagnosed based on increased liver echogenicity in ultrasound and elevated ALT activity), aged 14.5 years (range 8.5 to 15.8); 33 children with overweight/obesity without MASLD, aged 13.0 years (range 11.4 to 15.8); and 16 healthy controls aged 11.0 years (range 7.0 to 16.2). Defensin, I-FABP, and L-FABP levels were measured using commercial kits: ELISA kits (Drg Medtek) were used to assess α-5 and α-6 defensin concentrations (HBD5, HBD6). I-FABP and L-FABP concentrations were measured using commercial ELISA kits (Hycult Biotech Inc., Wayne, PA, USA). ANOVA analysis was used to compare results across the three study groups. Results: A significant difference was found for the following tests among children with MASLD, obesity, and healthy controls: defensin 6 (14.4 ng/mL vs. 6.13 ng/mL vs. 17.2 ng/mL, respectively), L-FABP (9168 pg/mL vs. 7954 pg/mL vs. 7620 pg/mL, respectively), and I-FABP (272 pg/mL vs. 321 pg/mL vs. 330 pg/mL, respectively). No differences were found in defensin 5 levels (median 567.2 pg/mL vs. 485.7 pg/mL vs. 601.8 pg/mL). No differences were observed in cholesterol levels (HDL, LDL) or triglyceride concentrations, as well as apolipoprotein levels. Conclusions: Based on our study, it was concluded that inflammation and intestinal barrier damage lead to increased L-FABP levels, as it is released from enterocytes in response to oxidative stress or tissue damage. Defensin 6 may indirectly affect L-FABP through microbiota regulation and protection of the intestinal barrier. Defensin 6 also exerts antimicrobial activity and may accompany liver inflammation, with its increased concentration in comparison to obesity explained by the activation of defense mechanisms.

Exercise and diet modulate the gut microbiota, which is involved in the regulation of orthopaedic diseases and synthesises a wide range of metabolites that modulate cellular function and play an important role in bone development, remodelling and disease. G protein-coupled receptors (GPCRs), the largest family of transmembrane receptors in the human body, interact with gut microbial metabolites to regulate relevant pathological processes. This paper provides a review of different dietary and exercise effects on the pathogenic gut microbiota and their metabolites associated with GPCRs in orthopaedic diseases. RESULTS: Generally, metabolites produced by gut microbiota contribute to the maintenance of bone health by activating the corresponding GPCRs, which are involved in bone metabolism, regulation of immune response, and maintenance of gut flora homeostasis. Exercise and diet can influence gut microbiota, and an imbalance in gut microbiota homeostasis can trigger a series of adverse immune and metabolic responses by affecting GPCR function, ultimately leading to the onset and progression of various orthopaedic diseases. Understanding these relationships is crucial for elucidating the pathogenesis of orthopaedic diseases and developing personalised probiotic-based therapeutic strategies. In the future, we should further explore how to prevent and treat orthopaedic diseases through GPCR-based modulation of gut microbes and their interactions. The development of substances that precisely modulate gut microbes through different exercises and diets will provide more effective interventions to improve bone health in patients.

Group B Streptococcus is a significant cause of early-onset disease in term newborns, with a global incidence of 0.41/1000 live births. Intrapartum antibiotic prophylaxis (IAP) has reduced EOD incidence by over 80%, but concerns exist about its impact on the neonatal gut microbiome and potential long-term health effects.

This single center study examines the effects of IAP on the fecal infant microbiome in the first year of age and on the T cell phenotype in the first days after birth among 22 infants receiving IAP with penicillin due to maternal GBS colonization and 26 infants not exposed to IAP. The fecal microbiome was analyzed at birth, one month and one year of age through 16S rRNA gene sequencing. Additionally, a T cell phenotyping of peripheral blood was performed between the second and fifth day of age.

At one month, IAP exposed infants had a significantly lower relative abundance of Bifidobacterium longum in fecal samples, an effect which was sustained at one year. In IAP exposed infants we found a proinflammatory T-helper cell profile, characterized by higher IL-17A, RORgt, and TGF-b expression.

This study proposes a sustained impact of IAP on the neonatal microbiome and T cell repertoire.

Despite established links between the infant gut microbiome and health, how complementary feeding shapes colonization remains unclear. Using FoodSeq, a DNA-based dietary assessment technique, we surveyed food intake across 729 children (0-3 y) from North and Central America, Africa, and Asia. We detected 199 unique plant food sequences, with only eight staples shared across all countries. Despite this global variation, early-life diets followed a common trajectory: weaning stage emerged as the dominant dietary signature across populations. Crucially, dietary diversity did not correlate with gut microbial diversity. Instead, dietary diversity and weaning stage specifically predicted the abundance of adult-associated bacteria. Our findings support a two-stage maturation model: an initial milk-dominated phase, followed by a diet-responsive phase that yields adult-like communities. Monitoring and promoting plant dietary diversity may thus support timely microbiome maturation worldwide.

Prolonged breastfeeding (BF), as opposed to artificial infant formula feeding (FF), has been shown to prevent the development of obesity later in life. The aim of our narrative review is to investigate the missing molecular link between postnatal protein overfeeding-often referred to as the "early protein hypothesis"-and the subsequent transcriptional and epigenetic changes that accelerate the expansion of adipocyte stem cells (ASCs) in the adipose vascular niche during postnatal white adipose tissue (WAT) development. To achieve this, we conducted a search on the Web of Science, Google Scholar, and PubMed databases from 2000 to 2025 and reviewed 750 papers. Our findings revealed that the overactivation of mechanistic target of rapamycin complex 1 (mTORC1) and S6 kinase 1 (S6K1), which inhibits wingless (Wnt) signaling due to protein overfeeding, serves as the primary pathway promoting ASC commitment and increasing preadipocyte numbers. Moreover, excessive protein intake, combined with the upregulation of the fat mass and obesity-associated gene (FTO) and a deficiency of breast milk-derived microRNAs from lactation, disrupts the proper regulation of FTO and Wnt pathway components. This disruption enhances ASC expansion in WAT while inhibiting brown adipose tissue development. While BF has been shown to have protective effects against obesity, the postnatal transcriptional and epigenetic changes induced by excessive protein intake from FF may predispose infants to early and excessive ASC commitment in WAT, thereby increasing the risk of obesity later in life.

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.

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.

Microplastics (MPs) and antibiotics are pervasive pollutants that may pose a risk to human health. Studies have shown that both MPs and antibiotics adversely affect lipid metabolism and increase the risk of obesity. However, it remains unclear whether combined exposure to these pollutants intensify the cumulative detrimental effect on obesity and metabolism. This study demonstrated the impact of exposure to polystyrene MPs (PS, 25 nm) and ciprofloxacin (CIP), both individually and combined, for 30 d and 90 d on the hepatic metabolism of male C57BL/6J mice. The results showed that mice exposed to PS and CIP for either 30 d or 90 d exhibited lipid metabolism disorders such as increased body weight, enlarged adipocytes, triglyceride accumulation in the liver, and higher HDL-C. Differentially expressed hepatic proteins were identified via proteomic analysis. The findings indicated that exposure for 30 d caused abnormal bile acid (BA) secretion in the liver and inhibited the BA secretion pathway, which resulted in intrahepatic cholestasis. Furthermore, exposure for 90 d resolved cholestasis and reduced the overall number of differentially expressed proteins. Intestinal pathology revealed more severe damage after exposure for 30 d, while 90 d exposure decreased the adverse effect. Combined CIP and PS exposure caused damage to the organism. However, the adaptive capacity of the organism during prolonged exposure mitigated the damage caused by both, but did not imply the complete eradication of adverse effects. This study found that 90 d exposure to PS and CIP resulted in weight gain, possibly due to changes in the gut flora and suppressed energy metabolism. These results indicated that simultaneous exposure to CIP and PS exacerbated the adverse impact on the liver, causing short-term intrahepatic cholestasis. Prolonged exposure reduced the energy metabolism in the body, exhibiting varied toxicity outcomes and mechanisms at different exposure durations. This study offers novel insights into the effect of MPs and antibiotic CIP exposure on metabolic abnormalities and provides a scientific basis for assessing these risks. It also emphasizes that the adverse effect resulting from 30 d (short-term) toxic exposure may not persist and that long-term chronic toxicity needs warrants.

Interactions between the gut microbiome and bile acids are complex and are linked to outcomes in pediatric liver disease by mechanisms that are incompletely understood. In adults, primary bile acids are synthesized in the liver and secreted into the intestine, where complex communities of gut microbes deconjugate, oxidize, epimerize, and 7α-dehydroxylate bile acids into a diverse array of unconjugated, secondary, allo-, iso-, and oxo-bile acids. In contrast, the infant gut microbiota contains a simple, Bifidobacterium-dominant community that transitions to a more diverse, adult-like community as additional microbes colonize the gut. This microbial succession gradually confers deconjugation, oxidation, epimerization, and 7α-dehydroxylation activities that mature the bile acid pool from a profile dominated by primary bile acids early in life to a more diverse, adult-like bile acid profile in later childhood. Altered bile acid profiles in pediatric cholestatic disorders have the potential to change the developmental trajectory of the microbiome. Conversely, alterations in the gut microbiome may re-shape the bile acid pool and hepatic bile acid metabolism. Understanding the mechanisms underlying these interactions will increase our understanding of liver pathophysiology and will motivate new therapeutic strategies for pediatric hepatic disorders. This review aims to highlight differences between the pediatric and adult intestinal microbiome and bile acid pool, and to discuss interactions between gut microbes and bile acids that are critical in early life and that may impact outcomes in infants and children with cholestatic liver disease, including biliary atresia.

Microbial communities are not simply remnants of the past but dynamic entities that continuously evolve under the selective pressures of nature, reflecting the intricate and adaptive processes of evolution. The microbiota residing in the various regions of the human body has numerous roles in different physiological processes such as nutrition, metabolism, immune regulation, etc. In the zeal of achieving empirical insights into the ambit of the gut microbiome, the research over the years led to the revelation of reciprocal interaction between the gut microbiome and the cognitive functioning of the human body. Dysbiosis in the gut microbial composition disturbs the homeostatic cognitive functioning of the human body. This dysbiosis has been associated with various chronic diseases, including brain cancer, such as glioma, glioblastoma, etc. This review explores the mechanistic role of dysbiosis-mediated progression of brain cancers and their subtypes. Moreover, it demonstrates the regulatory role of microbial metabolites produced by the gut microbiota, such as short-chain fatty acids, amino acids, lipids, etc., in the tumour progression. Further, we also provide valuable insights into the microbiota mediating the efficiency of therapeutic regimens, thereby leveraging gut microbiota as potential biomarkers and targets for improved treatment outcomes.

Moringa oleifera Lamarck seeds (MOS) have been traditionally used in folk medicine and documented for their potential to alleviate type 2 diabetes symptoms, but the potential mechanisms are still unknown. The purpose of this article is to investigate the effects of MSAP (alkali-extracted polysaccharide from MOS) on diabetic rats by assessing its impact on the gut microbiome, diabetes-related biochemical markers, and fecal metabolomics. The results demonstrated that the fasting blood glucose, glucose tolerance, insulin resistance, insulin level and lipopolysaccharides (LPS) level in the rats treated with MSAP were all improved. Specifically, MSAP was found to modulate the composition and diversity of the gut microbiota, increasing the ratio of Firmicutes/Bacteroidetes, which enhanced the quantity of probiotic Lactobacillus and butyrate-producing bacteria, such as Roseburia, thereby reinforcing the intestinal epithelial barrier. Furthermore, fecal metabolomics indicates that MSAP actively regulates pathways closely associated with diabetes, including sphingolipid metabolism, amino acid synthesis and catabolism, retrograde endogenous cannabinoid signaling, and the modulation of TRP channels by inflammatory mediators. By integrating microbiome and metabolomics data, this study elucidated the mechanisms through which MSAP alleviates diabetes. In conclusion, the findings suggest that polysaccharides from MOS hold potential as a medicinal and edible homologous food for diabetes management.

The human gut harbors thousands of microbial species, each exhibiting significant inter-individual genetic variability. Although many studies have associated microbial relative abundances with human-health-related phenotypes, the substantial intraspecies genetic variability of gut microbes has not yet been comprehensively considered, limiting the potential of linking such genetic traits with host conditions. Here, we analyzed 32,152 metagenomes from 94 microbiome studies across the globe to investigate the human microbiome intraspecies genetic diversity. We reconstructed 583 species-specific phylogenies and linked them to geographic information and species' horizontal transmissibility. We identified 484 microbial-strain-level associations with 241 host phenotypes, encompassing human anthropometric factors, biochemical measurements, diseases, and lifestyle. We observed a higher prevalence of a Ruminococcus gnavus clade in nonagenarians correlated with distinct plasma bile acid profiles and a melanoma and prostate-cancer-associated Collinsella clade. Our large-scale intraspecies genetic analysis highlights the relevance of strain diversity as it relates to human health.

Atopic dermatitis is a chronic inflammatory skin condition with a higher incidence rate among children. In recent years, the role of the gut microbiota in the pathogenesis of atopic dermatitis has garnered increasing attention. This review systematically delineates the research advancements in the structural characteristics of the gut microbiota in children with atopic dermatitis and its influencing factors. Studies have revealed significant differences in the gut microbiota structure between children with atopic dermatitis and healthy controls, characterized by a reduction in microbial diversity, a decrease in beneficial bacteria, and an increase in harmful bacteria. Dietary patterns, environmental factors, birth patterns, antibiotic use, and gestational diabetes mellitus are factors could impact the gut microbiota hence influencing the susceptibility of children to atopic dermatitis. Moreover, this review explores the interplay between the gut microbiota and the immune system in atopic dermatitis, with the potential to inform more effective probiotic treatment strategies for children with atopic dermatitis.

The gut microbiome plays a vital role in human health, functioning as a metabolic organ that influences nutrient absorption and overall well-being. With growing evidence that dietary interventions can modulate the microbiome and improve health, this review examines whether healthcare systems should prioritize personalized microbiome-targeted therapies, such as probiotics, prebiotics, and microbiota transplants, over traditional pharmaceutical treatments for chronic diseases like obesity, diabetes, cardiovascular risk, and inflammatory conditions. A systematic review using Web of Science and Scopus databases was conducted, followed by a scientometric analysis. Key metabolic pathways, such as dietary fiber fermentation and short-chain fatty acid production, were explored, focusing on their impact on lipid and glucose metabolism. The interactions between microbial metabolites and the immune system were also investigated. Dietary interventions, including increased fiber and probiotic intake, show potential for addressing dysbiosis linked to conditions, such as type 2 diabetes, obesity, and autoimmune diseases. The review emphasizes the need to incorporate microbiome modulation strategies into clinical practice and research, calling for a multidisciplinary approach that integrates nutrition, microbiology, and biochemistry to better understand the gut microbiome's complex role in health.

Inteins can connect flanking external proteins into a new protein fragment and excise themselves. Here, we report the in situ splicing of proteins by engineered microbial consortia. This study pioneers a programmable microbial consortia platform enabling in situ protein splicing through split intein-mediated assembly. Engineered Escherichia coli with the ePop autolysis system release intein-fused protein fragments via synchronized lysis, while Pichia pastoris secretes complementary domains, enabling extracellular reconstitution directly in culture. With the application of integrating quorum-sensing controls and eukaryotic secretion pathways, this approach bypasses in vitro purification, supporting scalable one-pot synthesis of multiple functional proteins. The platform's versatility in logic computation and antibiotic resistance engineering highlights its potential for adaptive biomanufacturing and context-aware biomaterial design.

Early-life establishment of the gut microbiota plays a role in lifelong health, with disruptions linked to heightened risks of metabolic and immune disorders. Probiotic supplementation may be used to modulate the infant gut microbiome to promote favourable development. Here, we evaluate how Lab4B probiotic supplementation shapes the development of the infant gut microbiome over the first 6 months. Faecal samples collected from infants enrolled in PROBAT (ISRCTN26287422), a randomised, double-blind, placebo-controlled trial, were analysed using culture-dependent and -independent (16S rDNA and metagenomic shotgun sequencing) techniques to examine the composition, diversity, and metabolic capabilities of the microbiome, as well as the abundance of antimicrobial resistance genes (ARGs). Probiotic supplementation encouraged the development of a microbiome with a distinct composition characterised by elevated abundances of Bifidobacteriaceae in the first 6 weeks (p = 0.006) and Lactobacillaceae throughout the first 6 months (p < 0.05 at every 6-week time point), accelerated microbial diversification, reduced abundance of beta-lactam- and cephalosporin-resistance genes, and differences in predicted metabolic capabilities at the start and end points. Supplementation of this neonatal population, which is at high risk of atopy, with the Lab4B probiotic significantly influenced the development of the infant gut microbiota during the first 6 months.

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.

Hypertensive disorders of pregnancy (HDP) pose significant risks to both maternal and fetal health and have been associated with alterations in the maternal gut microbiota. However, the impact of HDP on neonatal microbiota remains poorly understood. This study aimed to characterize the gut microbiota of pregnant women with HDP and evaluate its potential influence on the meconium microbiota of their newborns.

A cohort of 67 pregnant women, including 36 diagnosed with HDP (HDP group) and 31 healthy, age-matched controls (HC group), along with their offspring, were recruited. Fecal samples collected during the third trimester and meconium samples from the newborns were subjected to microbial community profiling via 16S rRNA gene sequencing.

Principal coordinate analysis (PCoA) based on Bray-Curtis distances revealed significant differences in microbial community composition between the HDP and HC groups in both maternal and neonatal samples. Subgroup analyses, stratified by HDP severity and medication use, further delineated distinct microbial profiles relative to controls. Notably, both maternal and neonatal microbiota in the HDP group exhibited increased abundances of Enterobacter, Klebsiella, and Sphingomonas, coupled with a reduction in Acidovorax, Azospirillum, Caulobacter, Flavobacterium, Magnetospirillum, and Rubrivivax compared to the HC group. Moreover, the P4-PWY pathway, which is involved in the biosynthesis of L-lysine, L-threonine, and L-methionine, was differentially represented in both maternal and neonatal microbiota in the HDP group. These parallel patterns suggest an intergenerational concordance associated with HDP.

This study demonstrates significant alterations in the microbial communities of both maternal fecal and neonatal meconium samples in the context of HDP. The findings highlight the importance of further research to elucidate the long-term health implications of HDP-associated microbiota shifts on offspring.

Background and Aim: The human gut microbiome plays a crucial role in maintaining health. Artificial sweeteners, also known as non-nutritive sweeteners (NNS), have garnered attention for their potential to disrupt the balance of the gut microbiome. This review explores the complex relationship between NNS and the gut microbiome, highlighting their potential benefits and risks. By synthesizing current evidence, we aim to provide a balanced perspective on the role of AS in dietary practices and health outcomes, emphasizing the need for targeted research to guide their safe and effective use. Methods: A comprehensive literature review was conducted through searches in PubMed and Google Scholar, focusing on the effects of artificial sweeteners on gut microbiota. The search utilized key terms including "Gut Microbiome", "gut microbiota", "Eubiosis", "Dysbiosis", "Artificial Sweeteners", and "Nonnutritive Sweeteners". Results: NNS may alter the gut microbiome, but findings remain inconsistent. Animal studies often report a decrease in beneficial bacteria like Bifidobacterium and Lactobacillus, and an increase in harmful strains such as Clostridium difficile and E. coli, potentially leading to inflammation and gut imbalance. Disruptions in short-chain fatty acid (SCFA) production and gut hormone signaling have also been observed. However, human studies generally show milder or no significant changes, highlighting the limitations in translating animal model findings directly to humans. Differences in study design, dosage, exposure time, and sweetener type likely contribute to these varied outcomes. Conclusions: While NNS offer certain benefits, including reduced caloric intake and improved blood sugar regulation, their impact on gut microbiome health raises important concerns. The observed reduction in beneficial bacteria and the rise in pathogenic strains underscore the need for caution in NNS consumption. Furthermore, the disruption of SCFA production and metabolic pathways illustrates the intricate relationship between diet and gut health.

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.

Breastfeeding is a major determinant of gut microbiota composition and fermentation activity during the first months of life. Breastmilk delivers human milk oligosaccharides (HMO) as substrates for microbial intestinal fermentation. One of the main metabolites that accumulates in feces of breastfed infants is 1,2-propanediol (1,2PD) resulting from the metabolism of fucosylated HMO. 1,2PD is used in microbial cross-feeding to produce propionate, but 1,2PD is also an alcohol that can impact the state of the microbial cell envelope. To shed further light on an understudied compound in the infant gut, we investigated the genetic and metabolic potential of the early gut colonizer Clostridium perfringens to utilise 1,2PD, and the interactions of 1,2PD with the cell envelope.

Based on genome analysis, C. perfringens FMT 1006 isolated from infant feces possessed most genes of the pdu operon related to 1,2PD metabolism. C. perfringens consumed 1,2PD (78%) and produced 1-propanol as the main metabolite, while propionate was not detected. In agreement, genes responsible for 1,2PD utilisation and propanol formation (pduCDE, dhaT) were highly expressed. When cultivated in the presence of 1,2PD and glucose, a higher proportion of 1,2PD carbon (87%) was recovered as compared to incubation with only 1,2PD (34%). At the same time, lactate and acetate were formed in a ratio of 2.16:1.0 with 1,2PD and glucose compared to a ratio 9.0:1.0 during growth with only glucose possibly due to reallocation of the NAD+/NADH pool in favor of 1-propanol formation. The presence of 1,2PD slightly increased membrane fluidity and modified the composition of the membrane to a higher content of elongated glycerophosphoethanolamines.

We provide here new knowledge on the metabolism of 1,2PD by a microbial species that is present during breastfeeding and observed that C. perfringens metabolised 1,2PD mainly to propanol. The presence of 1,2PD had little impact on membrane fluidity and let to modifications of membrane lipid composition. Collectively, these findings advance our understanding of on intestinal metabolite-microbe interactions during breastfeeding.

This study aims to investigate whether human milk exosomes from gestational diabetes mellitus (GDM-EXO) and healthy (HEA-EXO) parturients differ in regulating intestinal development in offspring. The differential miRNAs associated with intestinal development in GDM-EXO and HEA-EXO were verified by using qPCR and their relationships with gut microbiota (GM) in infants were analyzed. C57BL/6J mice were gavaged with 50 mg/kg·BW HEA-EXO or GDM-EXO. The intestinal morphology, gut barriers, ZO-1 and Occludin, and GM were determined by histological staining, Western blotting, and 16S rDNA amplicon sequencing, respectively. Hsa-miR-19b-3p, hsa-miR-148a-3p, and hsa-miR-320a-3p were upregulated, and hsa-miR-429 was decreased in GDM-EXO compared to HEA-EXO. The GDM parturients' infants had increased intestinal Coriobacteriaceae, Clostridiaceae, Erysipelotrichaceae, Erysipelatoclostridiaceae, and fewer Lactobacillaceae than the healthy parturient's infants. The four differential miRNAs in GDM-EXO all correlated with the infants' GM. GDM-EXO- and HEA-EXO-fed mice had greater villus lengths, villus length-to-crypt depth ratios, goblet cell numbers, elevated ZO-1 and Occludin, and lower crypt depths than control mice. HEA-EXO-fed mice had better intestinal morphology and gut barrier integrity than GDM-EXO-fed mice. GDM-EXO-fed mice had significantly decreased Lachnospiraceae and Oscillospiraceae than HEA-EXO-fed mice. GDM-EXO demonstrate weaker ability to promote intestinal development in offspring than HEA-EXO.