Maternal colonization with Group B Streptococcus (GBS) disrupts the vaginal microbiota, potentially affecting infant microbiota assembly and growth. While the gut microbiota's importance in infant growth is recognized, the specific effects of maternal GBS on growth remain unclear. This study aimed to explore the effects of maternal vaginal GBS during pregnancy on early infant growth, microbiome, and metabolomics.

We recruited and classified 453 pregnant women from southern China into GBS or healthy groups based on GBS vaginal colonization. Their infants were categorized as GBS-exposed or GBS-unexposed groups. We comprehensively analyzed infant growth, gut microbiota, and metabolites during early life, along with maternal vaginal microbiota during pregnancy, using 16S rDNA sequencing and targeted metabolomics.

GBS-exposed infants exhibited lower length-for-age z-scores (LAZ) than GBS-unexposed infants, especially at 2 months. Altered gut microbiota and metabolites in GBS-exposed infants correlated with growth, mediating the impact of maternal GBS on infant LAZ. Changes in the vaginal microbiota of the GBS group during the third trimester correlated with infant LAZ. Additionally, differences in neonatal gut microbiota, metabolites, and vaginal microbiota during pregnancy were identified between infants with overall LAZ<-1 within 8 months after birth and their counterparts, enhancing the discriminatory power of fundamental data for predicting the occurrence of LAZ<-1 during the first 8 months of life.

GBS exposure is associated with decreased infant length growth, with altered microbiota and metabolites potentially mediating the effects of maternal GBS on offspring length growth, offering potential targets for predicting and addressing growth impairment.

The gut microbiome comprises trillions of microorganisms and profoundly influences human health by modulating metabolism, immune responses and neuronal functions. Disruption in gut microbiome composition is implicated in various inflammatory conditions, metabolic disorders and neurodegenerative diseases. However, determining the underlying mechanisms and establishing cause and effect is extremely difficult. Preclinical models offer crucial insights into the role of the gut microbiome in diseases and help identify potential therapeutic interventions. The Human Microbiome Action Consortium initiated a Delphi survey to assess the utility of preclinical models, including animal and cell-based models, in elucidating the causal role of the gut microbiome in these diseases. The Delphi survey aimed to address the complexity of selecting appropriate preclinical models to investigate disease causality and to study host-microbiome interactions effectively. We adopted a structured approach encompassing a literature review, expert workshops and the Delphi questionnaire to gather insights from a diverse range of stakeholders. Experts were requested to evaluate the strengths, limitations, and suitability of these models in addressing the causal relationship between the gut microbiome and disease pathogenesis. The resulting consensus statements and recommendations provide valuable insights for selecting preclinical models in future studies of gut microbiome-related diseases.

Sarcopenia is an age-related muscle disorder that increases risks of adverse clinical outcomes, but its treatments are still limited. Gut microbiota is potentially associated with sarcopenia, and its role is still unclear. To investigate the role of gut microbiota in sarcopenia, we first compared gut microbiota and metabolites composition in old participants with or without sarcopenia. Fecal microbiota transplantation (FMT) from human donors to antibiotic-treated recipient mice was then performed. Specific probiotics and their mechanisms to treat aged mice were identified. Old people with sarcopenia had different microbial composition and metabolites, including Paraprevotella, Lachnospira, short-chain fatty acids, and purine. After FMT, mice receiving microbes from people with sarcopenia displayed lower muscle mass and strength compared with those receiving microbes from non-sarcopenic donors. Lacticaseibacillus rhamnosus (LR) and Faecalibacterium prausnitzii (FP) were positively related to muscle health of old people, and enhanced muscle mass and function of aged mice. Transcriptomics showed that genes related to tricarboxylic acid cycle (TCA) were enriched after treatments. Metabolic analysis showed increased substrates of TCA cycle in both LR and FP supernatants. Muscle mitochondria density, ATP content, NAD+/NADH, mitochondrial dynamics and biogenesis proteins, as well as colon tight junction proteins of aged mice were improved by both probiotics. LR and the combination of two probiotics also benefit intestinal immune health by reducing CD8+ IFNγ+ T cells. Gut microbiota dysbiosis is a pathogenesis of sarcopenia, and muscle-related probiotics could alleviate age-related muscle disorders mainly through mitochondria improvement. Further clinical translation is warranted.

The ARFID InitiativE Sweden (ARIES) investigates the genetic and environmental factors contributing to avoidant/restrictive food intake disorder (ARFID) in children and adolescents aged 6-14 years. ARIES will establish a national biobank and research registry. It aims to provide data for immediate research and track ARFID outcomes and clarify genetic links between ARFID and other conditions and analyse the gut microbiome to guide nutrition interventions.

The study will involve 1500 Swedish children and adolescents with ARFID and a control group of 500 Swedish children and adolescents without ARFID. Parents/guardians and their children will complete online questionnaires assessing ARFID and other eating disorder (ED) pathology, co-occurring conditions, quality of life and parental stress and ED pathology. All participants will provide a saliva sample for comprehensive genetic analyses. Additionally, a subset of participants will provide a stool sample to investigate the gut microbiome in ARFID.

ARIES was approved by the Swedish Ethical Review Authority (Dnr 2023-04638). All participants will give assent and their parents will complete informed consent. Data will be made available by the authors on reasonable request. Findings will be published in scientific journals and shared with the public and stakeholders in accessible ways, for example, via social media.

Mammalian gut microbiomes are highly dynamic communities that shape and are shaped by host aging, including age-related changes to host immunity, metabolism, and behavior. As such, gut microbial composition may provide valuable information on host biological age. Here, we test this idea by creating a microbiome-based age predictor using 13,563 gut microbial profiles from 479 wild baboons collected over 14 years. The resulting 'microbiome clock' predicts host chronological age. Deviations from the clock's predictions are linked to some demographic and socio-environmental factors that predict baboon health and survival: animals who appear old-for-age tend to be male, sampled in the dry season (for females), and have high social status (both sexes). However, an individual's 'microbiome age' does not predict the attainment of developmental milestones or lifespan. Hence, in our host population, gut microbiome age largely reflects current, as opposed to past, social and environmental conditions, and does not predict the pace of host development or host mortality risk. We add to a growing understanding of how age is reflected in different host phenotypes and what forces modify biological age in primates.

The pathogenesis of non-organic anorexia in children is not clear. This study intends to analyze intestinal bacteria to provide a relevant theoretical basis for the clinical rational selection of microecological agents. In the present study, children with non-organic anorexia were included in the anorexia group and normal healthy children in the control group. Stool samples were collected for the bioinformatics analysis after PCR and high-throughput sequencing. The results showed that the Ace, Chao, and Shannon indexes in the anorexia group were higher than those in the control group, while the Simpson index in the control group was lower than in the anorexia group. There were 14 taxa in the anorexia group and 11 taxa in the healthy control group at the phylum level, and 193 taxa in the anorexia group and 180 in the control group at the genus level. The dominant bacteria at the phylum level of the two groups were the same, while there were 16 dominant bacteria taxa in the anorexia group and 17 in the control group at the genus level. The ratio of percentage abundance of Bacteroidetes to that of Firmicutes (the B/F index) in the anorexia group was higher than in the control group. The abundance of Bacteroidetes in the anorexia group was higher than that in the control group, and the abundance of Actinomycetes in the control group was higher than that in the anorexia group. There were significant differences in 14 dominant genera between the two groups at the genus classification level. The LEfSe multilevel species difference analysis showed that at the phylum level, the significant influential bacterial taxa in the anorexia group were Bacteroidetes and Actinobacteria in the control group. At the genus level, the significant influential bacterial taxa in the anorexia group were Bacteroides, Faecalibacterium, and Subdoligranulum, and Bifidobacterium, Blautia, Streptococcus, Lachnoclostridium, and Erysipelatoclostridium in the control group. We conclude that the increase in Bacteroides abundance or in the B/F index and the reduction in Bifidobacterium abundance were related to the pathogenesis of anorexia.

Gut microbial essential amino acid (EAA) provisioning to mammalian hosts remains a critical yet poorly understood aspect of host-microbe nutritional interactions, with significant implications for human and animal health. To investigate microbial EAA contributions in mice with reconstituted gut microbiomes, we analyzed stable carbon isotopes (13C) of six EAAs across multiple organs. Germ-free (GF) mice fed a high-protein diet (18%) were compared to conventionalized (CVZ) mice fed a low-protein diet (10%) following fecal microbiota transplantation 30 days prior and a 20-day dietary intervention. We found no evidence for microbial EAA contributions to host tissues, with 13C-EAA fingerprinting revealing nearly identical patterns between GF and CVZ organs. Both groups maintained their expected microbiome statuses, with CVZ gut microbiota dominated by Firmicutes and Bacteroidetes phyla. These findings raise important questions about the functional capacities of reconstituted gut microbiomes. Future studies should investigate longer adaptation periods, varied dietary protein levels, and complementary analytical techniques to better understand the context-dependent nature of microbial EAA provisioning in mammalian hosts.

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

This study aims to compare the composition of GM isolated from individuals with AIS or congenital scoliosis (CS) and age-matched control (Ctr).

A total of 48 patients with AIS, 24 patients with CS, and 31 healthy individuals were recruited as the discovery cohort, and 9 pairs of siblings where one was affected by AIS were recruited as the validation cohort. The GM profile was determined with 16S rRNA sequencing, and the alpha-diversity and beta-diversity metrics were performed with Mothur. Linear discriminant analysis (LDA) analysis was performed to identify the enriched species.

The α diversity (Chao1 index) was significantly lower in AIS patients with low BMI (< 18.5) than those with normal BMI. The PcoA analysis showed a trend of clustering of GM in AIS compared to that in Ctr and CS groups (r2 = 0.0553, p = 0.001). METASTAT analysis showed Cellulomonadaceae was significantly enriched in AIS groups compared to CS and Ctr. LDA analysis showed 9 enriched species in AIS patients. Compared to Ctr, two species including Hungatella genus and Bacteroides fragilis were significantly enriched, while the Firmicutes versus Bacteroidetes (F/B) ratio and the Ruminococcus genus were significantly decreased in AIS but not CS groups. The significantly reduced F/B ratio and Ruminococcus genus in AIS were replicated in the validation cohort.

Our study elucidated an association between low BMI and GM diversity in AIS patients. The reduced F/B ratio and Ruminococcus genus in AIS patients were identified and validated in 9 pairs of AIS patients and their unaffected siblings. Our pilot results may help understand the anthropometric discrepancy in these patients and support a possible role of GM in the pathogenesis of AIS.

The human gut microbiome plays a crucial role in regulating intestinal and systemic health, impacting host immune response and metabolic function. Dysbiosis of the gut microbiome is linked to various diseases, including steatotic liver diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), a chronic liver disease characterized by excess hepatic lipid content and impaired metabolism, is the leading cause of liver disease worldwide. Among the gut microbes, Ruminococcus gnavus (R. gnavus) has garnered attention for its association with inflammatory and metabolic diseases. While R. gnavus abundance correlates to liver fat accumulation, further research is needed to identify a causal role or therapeutic intervention in steatotic liver disease. This review surveys our current understanding of R. gnavus in the development and progression of steatotic liver diseases, highlighting its potential mechanisms through metabolite secretion, and emphasizes the need for comprehensive microbiome analyses and longitudinal studies to better understand R. gnavus' impact on liver health. This knowledge could pave the way for targeted interventions aimed at modulating gut microbiota to treat and prevent MASLD and its comorbidities.

The emergence of cancer immunotherapy has revolutionized cancer treatment, offering remarkable outcomes for patients across various malignancies. However, the heterogeneous response to immunotherapy underscores the necessity of understanding additional factors influencing treatment efficacy. Among these factors, the human microbiota has garnered significant attention for its potential role in modulating immune response. Body: This review explores the intricate relationship between the human microbiota and cancer immunotherapy, highlighting recent advances and potential mechanisms underlying microbial influence on treatment outcomes.

Insights into the microbiome's impact on immunotherapy response not only deepen our understanding of cancer pathogenesis but also hold promise for personalized therapeutic strategies aimed at optimizing patient outcomes.

Background: The complementary feeding period, spanning from 6 to 24 months of age, marks the transition from an exclusive liquid diet in infants to a dietary pattern requiring the introduction of solid foods to meet nutritional demands. Complementary feeding coincides with other critical development windows, including the maturation of the gut microbiome. However, the effects of specific solid foods on gut microbiota and the subsequent influence on health outcomes require further investigation. Methods: This narrative review analyzes published research from January 2004 to October 2024 and aims to summarize the current evidence of the effects of complementary feeding on the infant gut microbiota. Results: A total of 43 studies were included in this review. Overall, multiple studies reported an increase in alpha-diversity after solid food introduction. Bifidobacteriaceae is the predominant bacterial family during the first 6 months of life, shifting to Lachnospiraceae, Ruminococcaceae, and Clostridium spp. after the introduction of solid foods. The timing of solid food introduction may also influence gut microbiota, though results were inconclusive. The effect of individual dietary components on the gut microbiota was conflicting, with limited evidence to make inferences. Conclusions: Because of variations in study design, dietary intake quantification, and minimal follow-up, a lack of conclusive evidence exists describing the relationship between complementary feeding and gut microbiota outcomes in infants. Future research to describe these relationships should focus on the impact of individual foods on microbial diversity and maturation, as well as the relationship between microbiota and infant health outcomes.

The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality.

We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births.

The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics.

The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments.

The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

In India, currently, there are no standard guidelines for the management of moderate acute malnutrition (MAM). Previous research in Bangladesh has shown that children with MAM have impaired gut microbiota development, and microbiota-directed complementary foods (MDCF) can potentially repair their gut microbiota.

The objectives of this study were to evaluate the acceptability and safety of supplementing shelf-stable formulation of MDCF in Indian children with MAM as compared with a locally prepared ready-to-use supplementary food (RUSF) in 3 geographically distinct Indian populations and to establish and pilot systems of intervention delivery, collection, transport, and storage of stool samples using stringent protocols.

This pre-proof-of-concept (prePOC), multicentric, open-labeled, age-stratified, randomized controlled trial was done in children aged 6-18 mo with MAM. After a run-in period of 2 wk, the participants were supplemented with MDCF or RUSF for 4 wk through direct observation and followed up for another 2 wk post intervention. Maternal responses to the acceptability of the organoleptic properties of supplements were recorded weekly during the intervention phase of 4 wk. Compliance was reported based on the amount of supplement consumed by the children. Feasibility of weekly stool sample collection (except 7th week) within 30 min of passage was recorded. Anthropometric measurements were done at baseline and endline. Monitoring for adverse events was done throughout the course of the study.

A total of 240 children with MAM were randomly selected to receive either MDCF or RUSF, of which 221 (92.1%) completed follow-up. The overall acceptability for >80% of the maternal responses was reported as good or very good for all organoleptic properties in both MDCF and RUSF arms. MDCF and RUSF interventions had good-to-high compliance in 83.0% and 79.8% of participants, respectively. At the end of the intervention phase, 53.2% (58/109) of children in MDCF arm against 42.0% (47/112) in RUSF arm had weight-for-length Z score >-2. The overall incidence of acute gastroenteritis reported was low; higher in MDCF compared with RUSF but not statistically significant.

The prePOC study demonstrates good acceptability and safety of MDCF among Indian children with MAM including the age group of 6-12 mo of age. The study demonstrates the feasibility of conducting a long-term supplementation study in this population. The study was registered at the clinical trial registry of India as CTRI/2023/01/048716.

There is growing interest in members of the genus Segatella (family Prevotellaceae) as members of a well-balanced human gut microbiota (HGM). Segatella are particularly associated with the consumption of a diet rich in plant polysaccharides comprising dietary fiber. However, understanding of the molecular basis of complex carbohydrate utilization in Segatella species is currently incomplete. Here, we used RNA sequencing (RNA-seq) of the type strain Segatella copri DSM 18205 (previously Prevotella copri CB7) to define precisely individual polysaccharide utilization loci (PULs) and associated carbohydrate-active enzymes (CAZymes) that are implicated in the catabolism of common fruit, vegetable, and grain polysaccharides (viz. mixed-linkage β-glucans, xyloglucans, xylans, pectins, and inulin). Although many commonalities were observed, several of these systems exhibited significant compositional and organizational differences vis-à-vis homologs in the better-studied Bacteroides (sister family Bacteroidaceae), which predominate in post-industrial HGM. Growth on β-mannans, β(1, 3)-galactans, and microbial β(1, 3)-glucans was not observed, due to an apparent lack of cognate PULs. Most notably, S. copri is unable to grow on starch, due to an incomplete starch utilization system (Sus). Subsequent transcriptional profiling of bellwether Ton-B-dependent transporter-encoding genes revealed that PUL upregulation is rapid and general upon transfer from glucose to plant polysaccharides, reflective of de-repression enabling substrate sensing. Distinct from previous observations of Bacteroides species, we were unable to observe clearly delineated substrate prioritization on a polysaccharide mixture designed to mimic in vitro diverse plant cell wall digesta. Finally, co-culture experiments generally indicated stable co-existence and lack of exclusive competition between S. copri and representative HGM Bacteroides species (Bacteroides thetaiotaomicron and Bacteroides ovatus) on individual polysaccharides, except in cases where corresponding PULs were obviously lacking.

There is currently a great level of interest in improving the composition and function of the human gut microbiota (HGM) to improve health. The bacterium Segatella copri is prevalent in people who eat plant-rich diets and is therefore associated with a healthy lifestyle. On one hand, our study reveals the specific molecular systems that enable S. copri to proliferate on individual plant polysaccharides. On the other, a growing body of data suggests that the inability of S. copri to grow on starch and animal glycans, which dominate in post-industrial diets, as well as host mucin, contributes strongly to its displacement from the HGM by Bacteroides species, in the absence of direct antagonism.

Knowledge of the complex interplay between gut microbiota and human health is gradually increasing as it has just recently been a field of such great interest.

Recent studies have reported that communities of microorganisms inhabiting the gut influence the immune system through cellular responses and shape many physiological and pathophysiological aspects of the body, including muscle and bone metabolism (formation and resorption). Specifically, the gut microbiota affects skeletal homeostasis through changes in host metabolism, the immune system, hormone secretion, and the gut-brain axis. The major role on gut-bone axis is due to short-chain fatty acids (SCFAs). They have the ability to influence regulatory T-cell (Tregs) development and activate bone metabolism through the action of Wnt10. SCFA production may be a mechanism by which the microbial community, by increasing the serum level of insulin-like growth factor 1 (IGF-1), leads to the growth and regulation of bone homeostasis. A specific SCFA, butyrate, diffuses into the bone marrow where it expands Tregs. The Tregs induce production of the Wnt ligand Wnt10b by CD8+ T cells, leading to activation of Wnt signaling and stimulation of bone formation. At the hormonal level, the effect of the gut microbiota on bone homeostasis is expressed through the biphasic action of serotonin. Some microbiota, such as spore-forming microbes, regulate the level of serotonin in the gut, serum, and feces. Another group of bacterial species (Lactococcus, Mucispirillum, Lactobacillus, and Bifidobacterium) can increase the level of peripheral/vascular leptin, which in turn manages bone homeostasis through the action of brain serotonin.

Early-life malnutrition adversely affects nearly all organ systems, resulting in multiple physiological adaptations, including growth restriction and muscle and bone loss. Although there is growing evidence that probiotics effectively improve systemic growth under malnourished conditions in different animal models, our knowledge of the beneficial effects of probiotics on various organs is limited. Here, we show that Lactobacillus plantarum strain WJL (LpWJL) can mitigate skeletal muscle and bone loss in protein-malnourished juvenile mice. Mice on prenatal day 21 were fed a protein-malnourished (P-MAL) diet with or without LpWJL supplementation for six weeks. Compared to mice on the P-MAL diet alone, LpWJL supplementation significantly increased muscle mass and size, resulting in enhanced muscle strength and endurance capacity. Furthermore, LpWJL supplementation induced the expression of the key growth factor IGF-1 while decreasing muscle atrophy markers such as Atrogin-1 and MuRF-1, indicating potential mechanisms by which protein malnutrition-induced muscle wasting is counteracted. Additionally, LpWJL supplementation alleviated the reduction in cortical bone thickness and the deterioration of trabecular bone microstructure in the femur. Taken together, these results indicate that LpWJL can protect against skeletal muscle atrophy and compromised bone microarchitecture caused by protein malnutrition, providing novel insights into the potential therapeutic applications of probiotics for treating malnutrition-related disorders.

Various dietary factors in human milk are important nutrients for the formation of the infant gut microbiota (GM). While promoting the growth of the GM, some human milk components that are difficult to absorb and utilize will be broken down by the GM, and converted into nutrients that the baby can use, such as breast milk oligosaccharides-the 'carbon source' for infant GM. This study reveals that nucleotides (NTs), significant non-protein nitrogen sources in human milk, can enhance the abundance of beneficial microbial genera such as g_Bifidobacterium, g_Bacteroides, and g_Blautia in in vitro fecal fermentation fluids of infants at low doses (2 mg/mL). Conversely, high doses of NTs (20 mg/mL) increased the abundance of g_Escherichia-Shigella. Furthermore, low-dose NTs fermentation broth significantly enhanced the expression of neurodevelopmental marker genes such as Tuj1, Sox2, Dcx, and NeuN in NE-4C neural stem cells, whereas a single NTs digestion broth did not exhibit significant activity. However, in vivo studies using neonatal rats as a model demonstrated that both low-dose NTs fermentation broth and NTs digestive juices promoted behavioral development in neonatal rats (PND 20) and neuron maturation in the prefrontal cortex and hippocampus. Non-targeted metabolomics results indicate that low-dose dietary NTs promote the production of certain neuroregulatory metabolites in infant fecal fermentation, such as uridine, L-tyrosine, L-glutamic acid, and succinic acid. These findings suggest that NTs may serve as an important "nitrogen source" during GM formation in early life and have a dose effect in driving the development of the microbiota-gut-brain axis in early life.

Aging is the main risk factor for developing cognitive impairments and associated neurodegenerative diseases. However, environmental factors, including nutritional health, are likely to promote or reduce cognitive impairments and neurodegenerative pathologies. An intricate relationship exists between maternal nutrition and adult eating behavior, metabolic phenotype, and cognitive abilities.

The objective of the present review was to collect available data, suggesting a link between maternal overnutrition and the latter impairment of cognitive functions in the progeny, and to relate this relationship with Alzheimer's disease (AD). Indeed, cognitive impairments are major behavioral signs of AD. We first reviewed studies showing an association between unbalanced maternal diet and cognitive impairments in the progeny in humans and rodent models. Then we looked for cellular and molecular hallmarks which could constitute a breeding ground for AD in those models. With this end, we focused on synaptic dysfunction, altered neurogenesis, neuroinflammation, oxidative stress, and pathological protein aggregation. Finally, we proposed an indirect mechanism linking maternal unbalanced diet and progeny's vulnerability to cognitive impairments and neurodegeneration through promoting metabolic diseases. We also discussed the involvement of progeny's gut microbiota in the maternal diet-induced vulnerability to metabolic and neurodegenerative diseases.

Further investigations are needed to fully decipher how maternal diet programs the fetus and infant brain. Addressing this knowledge gap would pave the way to precise nutrition and personalized medicine to better handle cognitive impairments in adulthood.

The nutritional environment during fetal and early postnatal life has a long-term impact on growth, development, and metabolic health of the offspring, a process termed "nutritional programming." Rodent models studying programming effects of nutritional interventions use either purified or grain-based rodent diets as background diets. However, the impact of these diets on phenotypic outcomes in these models has not been comprehensively investigated. We used a previously validated (C57BL/6J) mouse model to investigate the effects of infant milk formula (IMF) interventions on nutritional programming. Specifically, we investigated the effects of maternal diet type (i.e., grain-based vs purified) during early lactation and prior to the intervention on offspring growth, metabolic phenotype, and gut microbiota profile. Maternal exposure to purified diet led to an increased post-weaning growth velocity in the offspring and reduced adult diet-induced obesity. Further, maternal exposure to purified diet reduced the offspring gut microbiota diversity and modified its composition post-weaning. These data not only reinforce the notion that maternal nutrition significantly influences the programming of offspring vulnerability to an obesogenic diet in adulthood but emphasizes the importance of careful selection of standard background diet type when designing any preclinical study with (early life) nutritional interventions.

Malnutrition affects over 30 million children annually and has profound immediate and enduring repercussions. Survivors often suffer lasting neurocognitive consequences that impact academic performance and socioeconomic outcomes. Mechanistic understanding of the emergence of these consequences is poorly understood. Using multi-system SHAP interpreted random forest models and network analysis, we show that Moderate Acute Malnutrition (MAM) associates with enrichment of faecal Rothia mucilaginosa, Streptococcus salivarius and depletion of Bacteroides fragilis in a cohort of one-year-old children in Dhaka, Bangladesh. These microbiome changes form interconnected pathways that involve reduced plasma odd-chain fatty acid levels, decreased gamma and beta electroencephalogram power in temporal and frontal brain regions, and reduced vocalization. These findings support the hypothesis that prolonged colonization by oral commensal species delay gut microbiome and brain development. While causal links require empirical validation, this study provides insights to improve interventions targeting MAM-associated neurodevelopmental deficits.

Drought induced by climate change poses a serious threat to human health. The gut microbiome also plays a critical role in human health. However, no studies have explored the effect of drought on the human gut microbiome. Therefore, our study aimed to investigate the relationship between drought and gut microbiome. Our study included 59 mothers and 38 neonates in our study. 16S rRNA V3-V4 sequencing was used to profile the gut microbiome. The Standardized Precipitation Evapotranspiration Index (SPEI) was used to represent drought characteristics. KEGG pathway level 3 was employed for functional analysis. Generalized linear models were used to explore the effect of drought on the gut microbiome. Mothers and neonates were divided into the LSPEI (Lower SPEI) group or HSPEI (Higher SPEI) group by calculating the average levels of prenatal SPEI levels. The maternal and neonatal gut microbiome exhibited similar diversities in terms of alpha and beta diversity between the LSPEI and HSPEI groups. However, notable differences were observed in their composition. We found that in the neonatal gut microbiome, Sediminibacterium and Thermovirga were positively associated with SPEI after controlling for PM2.5 in linear regression models. Additionally, SPEI was significantly associated with phenylpropanoid biosynthesis and cyanoamino acid metabolism in neonates. This study identified that prenatal SPEI levels were correlated with specific maternal and neonatal gut microbial taxa, as well as neonatal gut microbial functional pathways. Future studies should further investigate the mechanisms by which drought exposure influences maternal and neonatal gut microbial diversities, composition, and functional pathways.

Bacteria are unicellular organisms with the ability to exist in the harshest of climate and cope with sub-optimal fluctuating environmental conditions. They accomplish this by modification of their internal cellular environment. When external conditions are varied, change in the cell is triggered at the transcriptional level, which usually leads to proteolysis and rewiring of the proteome. Changes in cellular homeostasis, modifications in proteome, and dynamics of such survival mechanisms can be studied using various scientific techniques. Our focus in this chapter would be on comparative proteomics of bacteria under stress conditions using approaches like 2D electrophoresis accompanied by N-terminal sequencing and recently, mass spectrometry. More than 170 such studies on bacteria have been accomplished till to date and involve analysis of whole cells as well as that of cellular fractions, i.e., outer membrane, inner membrane, cell envelope, cytoplasm, thylakoid, lipid bodies, etc. Similar studies conducted on gram-negative and gram-positive model organism, i.e., Escherichia coli and Bacillus subtilis, respectively, have been summarized. Vital information, hypothesis about conservation of stress-specific proteome, and conclusions are also presented in the light of research conducted over the last decades.

The infant gut microbiome undergoes rapid changes in the first year of life, supporting normal development and long-term health. Although diet shapes this process, the role of fibers in complementary foods on gut microbiome maturation is poorly understood.

We explored how the transition from human milk to fibers in complementary foods shapes the taxonomic and functional maturation of the gut microbiome within the first year of life.

We assessed the longitudinal and cross-sectional development of infant gut microbiomes (N = 68 infants) and metabolomes (N = 33 infants) using linear mixed models to uncover their associations to dietary fibers and their food sources. Fiber intakes were assessed with 3-d food records (months 3, 6, 9, and 12) relying on CODEX-compliant fiber fraction values, and questionnaires tracked the overall complementary food introduction. Bacterial species were identified and quantified via MetaPhlAn2 from metagenomic data, and metabolomic profiles were obtained using 4 LC-MS methods.

We identified 176 complementary food fiber-bacterial species associations. First plant-based fibers associated with microbiota compositions similar to breastfeeding, and further associated with aromatic amino acid-derived metabolites, including 5-hydroxyindoleacetic acid (total dietary fiber - complementary foods (g) - β = 3.50, CI: 2.48, 4.52, P = 6.53 × 10-5). Distinct fibers from different food categories showed unique associations with specific bacterial taxa. Key species, such as Faecalibacterium prausnitznii, associated with oat fibers (g/MJ, β = 2.18, confidence interval: 1.36, 2.84, P = 6.12 × 10-6), reflective of maturing microbial communities. Fiber intake during weaning associated with shifts in metabolite profiles, including immunomodulatory metabolites, with fiber effects observed in a source- and timing-dependent manner, implicated in gradual microbiome diversification.

Introducing complementary dietary fibers during the weaning period supports gut microbiome diversification and stabilization. Even minor dietary variations shows significant associations with microbial taxa and functions from the onset of weaning, highlighting the importance of infant dietary recommendations that support the gut microbiome maturation during early life. This trial was registered at clinicaltrials.gov as registration number NCT01735123.

Mammalian gut microbiomes are highly dynamic communities that shape and are shaped by host aging, including age-related changes to host immunity, metabolism, and behavior. As such, gut microbial composition may provide valuable information on host biological age. Here we test this idea by creating a microbiome-based age predictor using 13,563 gut microbial profiles from 479 wild baboons collected over 14 years. The resulting "microbiome clock" predicts host chronological age. Deviations from the clock's predictions are linked to some demographic and socio-environmental factors that predict baboon health and survival: animals who appear old-for-age tend to be male, sampled in the dry season (for females), and have high social status (both sexes). However, an individual's "microbiome age" does not predict the attainment of developmental milestones or lifespan. Hence, in our host population, gut microbiome age largely reflects current, as opposed to past, social and environmental conditions, and does not predict the pace of host development or host mortality risk. We add to a growing understanding of how age is reflected in different host phenotypes and what forces modify biological age in primates.

Sepsis is the body's extreme response to an infection leading to organ dysfunction. Sepsis-related acquired weakness (SAW), a critical illness closely related to metabolic disorders, is characterized by generalized sepsis-induced skeletal muscle weakness, mainly manifesting as symmetrical atrophy of respiratory and limb muscles. Muscle accounts for 40% of the body's total mass and is one of the major sites of glucose and energy absorption. Diet affects skeletal muscle metabolism, which further impacts physiology and signaling pathways. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that has shown benefits in patients with a variety of neuromuscular disorders. Patients with SAW are in a hypermetabolic state and can consume approximately 1% of total body muscle mass in a day. Due to the decreased total body energy expenditure secondary to starvation, skeletal muscles enter a low metabolic state, with reduced gluconeogenesis and protein consumption and elevated levels of ketone bodies. The latest research suggests that KD may be a new strategy for SAW prevention and treatment, but its mechanism is still unclear.

Our article aims to explore the effect and mechanism of KD on SAW. And we hope that our review will inspire further research on the KD and foster the exploration of novel strategies for combating SAW.

Search medical databases and related academic websites, using keywords such as "Sepsis-related acquired weakness," "ketogenic diet," and "skeletal muscle," and select representative literature. Using the method of induction and summary, analyze the effect and mechanism of KD on SAW.

Compared with early nutrition, KD has a more protective effect on SAW, but its mechanism is complex. Firstly, KD can alter energy metabolism substrates to affect SAW's energy metabolism; Secondly, KD can directly act as a signaling molecule to improve mitochondrial function in skeletal muscle and stimulate skeletal muscle regeneration signaling molecules; Thirdly, KD can affect the gut microbiota to exert anti-inflammatory effects, enhance immunity, and thus protect SAW.

KD has a protective effect on SAW, which includes improving energy metabolism, stimulating muscle regeneration signals, optimizing gut microbiota composition, and reducing inflammation and oxidative stress.

The anti-inflammatory and antimicrobial benefits of prebiotics may present an affordable and cost-effective strategy for not only the prevention but also treatment of malnutrition. Therefore, the present trial has been designed with the aim to evaluate the role of prebiotics on the gut microbiome of severe acute malnourished (SAM) children.

The study is designed as a prospective, double-blinded, triple-armed, multi-centered randomized controlled trial, with 6-59 months old uncomplicated SAM children recruited to the experimental group receiving ready-to-use therapeutic food (RUTF) plus prebiotics and the active comparator group receiving RUTF plus starch for 2 months duration (8 weeks). Healthy children with matching age and gender will be recruited to placebo comparator group and will receive starch as a placebo during the study period. A total of 58 participants will be recruited to each arm with 1:1:1 allocation ratio following a pre-defined inclusion and exclusion criteria. The results of the gut microbiome diversity will serve as the primary outcome, while weight-for-height/length z-score, mid-upper-arm circumference, neurodevelopment assessment, and body mass accumulation will serve as the secondary outcome. Data collection and evaluations will be conducted at baseline and at the end of the trial (week 8), while the safety monitoring will be conducted at every second week. For analysis, the principles of intention-to-treat will be followed.

Conclusively, the results of the present trial would provide useful insights and high-quality data for the treatment and management of SAM children by evaluating the effect of RUTF plus prebiotic on the gut microbiome diversity of children, leading to medical evidence for designing the large-scale studies.

The present trial is registered at ClinicalTrials.gov with identifier No: NCT06155474 and registration date 4 December 2023.

Despite efforts within the framework of the Sustainable Development Goal to end malnutrition by 2030, malnutrition and soil-transmitted helminth infections persist in sub-Saharan Africa. A significant barrier to success is the inadequate understanding of effective intervention methods. Most research on the gut microbiota's role in health has been conducted in developed countries, leaving a critical gap in knowledge regarding low-income populations. This study addresses this gap by expanding research on the gut microbiota of underprivileged populations to help tackle these public health challenges.

We employed 16S rDNA sequencing to assess the bacterial gut microbiota composition of 60 children (mean age: 26.63 ± 6.36 months) and their 58 mothers (mean age: 30.03 ± 6.31 years) in Pemba, with a focus on helminth infection and nutritional status.

Our differential abundance analysis identified bacterial taxa that were significantly negatively associated with both helminth infections and malnutrition, highlighting the potential for microbiota-directed interventions to address these health issues simultaneously. Notably, we identified Akkermansia, Blautia, Dorea, and Odoribacter as promising probiotic candidates for such interventions. In stunted children, positive co-occurrences were observed between Lactobacillus, Prevotella, and Bacteroides, while Escherichia/Shigella displayed negative co-abundance relationships with short-chain fatty acid (SCFA) producers in the gut microbiota. These findings suggest that administering Lactobacillus and SCFA-producing probiotics to children may foster the growth of beneficial bacteria like Prevotella and Bacteroides while reducing the relative abundance of Escherichia/Shigella, potentially enhancing overall health.

This study underscores the importance of microbiota-directed interventions in children and women of reproductive age as promising strategies, alongside established approaches, for combating helminth infections and malnutrition in vulnerable populations.

The gut microbiota has a profound effect on immunity and metabolic status of the host, which has increasingly attracted research communities. However, the intrinsic mechanism underlying the interplay among these three aspects remains unclear.

Different immune states were established via shaping the population structure of gut microbiota with antibacterial agents. The gut microbiota population structures altered with the subtherapeutic level of antibacterial agents facilitated growth phenotype in both piglets and infant mice. Notably, increased colonization of Prevotella copri was observed in the intestinal microbiota, which shifted the immune balance from a CD4+ T cell-dominated population toward a T helper 2 cell (Th2) phenotype, accompanied by a significant elevation of interleukin-13 (IL-13) levels in the portal vein, which was found to display a strong positive correlation with hepatic insulin-like growth factor-1 (IGF-1) levels. Subsequent investigations unveiled that gut-derived IL-13 stimulated the production of hepatic IGF-1 by activating the IL-13R/Jak2/Stat6 pathway in vitro. The IGF-1 levels were increased in the muscles, leading to an upregulation of and resulted the increased genes associated with related to myofibrillar synthesis and differentiation, which ultimately improving the growth phenotype.

Our findings highlight the modification of gut immunity states as a central strategy for increasing anabolism of the host, which has significant implications for addressing human undernutrition/stunting, sarcopenia, obesity and related comorbidities. Video Abstract.

The infant gut microbiome matures greatly in the first year of life. Ambient air pollution (AAP) exposure is associated with the infant gut microbiome. However, whether time-varying AAP influences infant gut microbiome variation is rarely investigated. This study aimed to investigate the effects of PM2.5, PM10, and O3 on infant gut microbiome variation longitudinally. Demographic information, stool samples, and AAP exposure concentrations were collected at 6, 12, 24 months from infants. Gut microbiome was processed and analyzed using 16S rRNA V3-V4 gene regions. AAP exposure concentrations were calculated using the China High Air Pollutants (CHAP) database. Multiple pollutant models were used to assess the mixed effects of PM2.5, PM10, and O3 on infant gut microbiome variation. Infants' gut microbiomes at 6, 12, 24 months old had significant differences in alpha diversity, beta diversity, and community composition. PM2.5 and O3 respectively explained 6.3% and 5.3% of the differences in community composition for 24-month-old infants. Single pollutant exposure and multiple pollutant exposure in different periods were both associated with alpha diversity indices and specific gut microbial phyla and genera. AAP was more associated with infant gut microbial alpha diversity indices, phyla variations, and genera variations at 12-24 months than 6-12 months. Multiple pollutant exposure in 0-2 lag months showed negative correlations with 12-24 months variation in Escherichia-Shigella (β = -0.854, 95%CI: 1.398 to -0.310) and Enterococcus (β = -0.979, 95%CI: 1.429 to -0.530). This study highlighted that time-varying PM2.5, PM10, and O3 synergistically influenced the variation of alpha diversity and abundance of gut microbial taxa in infants. Further research is needed to explore the effects and mechanisms of other environmental exposures on infant gut microbiome variation.

To profile the gut microbiome (GM) in infants with congenital heart disease (CHD) undergoing cardiac surgery compared with matched infants and to investigate the association with growth (weight, length, and head circumference).

A prospective study in the cardiac intensive care unit at Children's Healthcare of Atlanta and newborn nursery within the Emory Healthcare system. Characteristics including weight, length, head circumference, and surgical variables were collected. Fecal samples were collected presurgery (T1), postsurgery (T2), and before discharge (T3), and once for controls. 16 small ribosomal RNA subunit V4 gene was sequenced from fecal samples and classified into taxonomy using Silva v138.

There were 34 children with CHD (cases) and 34 controls. Cases had higher alpha-diversity, and beta-diversity showed significant dissimilarities compared with controls. GM was associated with lower weight and smaller head circumference (z-score < 2). Lower weight was associated with less Acinetobacter, Clostridioides, Parabacteroides, and Escherichia-Shigella. Smaller head circumference with more Veillonella, less Acinetobacter, and less Parabacteroides.

Significant differences in GM diversity and abundance were observed between infants with CHD and control infants. Lower weight and smaller head circumference were associated with distinct GM patterns. Further study is needed to understand the longitudinal effect of microbial dysbiosis on growth in children with CHD.

Recent years have witnessed major advances and an ever-growing list of healthcare applications for microbiome-based therapeutics. However, these advances have disproportionately targeted diseases common in high-income countries (HICs). Within low- to middle-income countries (LMIC), opportunities for microbiome-based therapeutics include sexual health epidemics, maternal health, early life mortality, malnutrition, vaccine response and infectious diseases. In this review we detail the advances that have been achieved in microbiome-based therapeutics for these areas of healthcare and identify where further work is required. Current efforts to characterise microbiomes from LMICs will aid in targeting and optimisation of therapeutics and preventative strategies specifically suited to the unmet needs within these populations. Once achieved, opportunities from disease treatment and improved treatment efficacy through to disease prevention and vector control can be effectively addressed using probiotics and live biotherapeutics. Together these strategies have the potential to increase individual health, overcome logistical challenges and reduce overall medical, individual, societal and economic costs.

Undernutrition in Bangladeshi children is associated with disruption of postnatal gut microbiota assembly; compared with standard therapy, a microbiota-directed complementary food (MDCF) substantially improved their ponderal and linear growth. Here, we characterize a fatty acid amide hydrolase (FAAH) from a growth-associated intestinal strain of Faecalibacterium prausnitzii cultured from these children. This enzyme, expressed and purified from Escherichia coli, hydrolyzes a variety of N-acylamides, including oleoylethanolamide (OEA), neurotransmitters, and quorum sensing N-acyl homoserine lactones; it also synthesizes a range of N-acylamides, notably N-acyl amino acids. Treating germ-free mice with N-oleoylarginine and N-oleolyhistidine, major products of FAAH OEA metabolism, markedly affected expression of intestinal immune function pathways. Administering MDCF to Bangladeshi children considerably reduced fecal OEA, a satiety factor whose levels were negatively correlated with abundance and expression of their F. prausnitzii FAAH. This enzyme, structurally and catalytically distinct from mammalian FAAH, is positioned to regulate levels of a variety of bioactive molecules.