Micronutrients have demonstrated promise in managing inattention and emotional dysregulation in children with attention-deficit/hyperactivity disorder (ADHD). One plausible pathway by which micronutrients improve symptoms is the gut microbiome. This study examines changes in fecal microbial composition and diversity after micronutrient supplementation in children with ADHD (N = 44) and highlights potential mechanisms responsible for the behavioral improvement, as determined by blinded clinician-rated global improvement response to micronutrients. Participants represent a sub-group of the Micronutrients for ADHD in Youth (MADDY) study, a double blind randomized controlled trial in which participants received micronutrients or placebo for 8 weeks, followed by an 8-week open extension. Stool samples collected at baseline, week 8, and week 16 were analyzed using 16S rRNA amplicon sequencing targeting the V4 hypervariable region. Pairwise compositional analyses investigated changes in fecal microbial composition between micronutrients versus placebo and responders versus non-responders. A significant change in microbial evenness, as measured by alpha diversity, and beta-diversity, as measured by Bray-Curtis, was observed following micronutrients supplementation. The phylum Actinobacteriota decreased in the micronutrients group compared to placebo. Two butyrate-producing bacterial families: Rikenellaceae and Oscillospiraceae, exhibited a significant increase in change following micronutrients between responders versus non-responders. These findings suggest that micronutrients modulated the composition of the fecal microbiota and identified specific bacterial changes associated with micronutrient responders.

Short-chain fatty acids (SCFAs) are a group of organic compounds produced by the fermentation of dietary fibre by the human gut microbiota. They play diverse roles in different physiological processes of the host with implications for human health and disease. This Review provides an overview of the complex microbial metabolism underlying SCFA formation, considering microbial interactions and modulating factors of the gut environment. We explore the multifaceted mechanistic interactions between SCFAs and the host, with a particular focus on the local actions of SCFAs in the gut and their complex interactions with the immune system. We also discuss how these actions influence intestinal and extraintestinal diseases and emerging therapeutic strategies using SCFAs.

Despite broad knowledge of the pathogenesis, our understanding of the origin of allergy and asthma remains poor, preventing etiotropic treatments. The gut microbiome is seen to be altered in asthmatics; however, proof of causality of the microbiome alterations is lacking. We report on gut microbiome transplantation (GMT) from mice predisposed to asthma by maternal exposure to pro-allergy environmental particles into naive recipients. This GMT confers asthma predisposition, and the effect is abrogated by gamma sterilization of the transplant material or by co-administration of antibacterials, indicating that viable bacteria are mediating the effect. Metagenomics identifies key changes in the "pro-asthma" microbiome, and metabolomics links the identified species to altered production of butyrate known to act on immune cells and epigenetic mechanisms. We further show that transplant recipients develop DNA methylation alterations in dendritic cells. Finally, dendritic cells with an altered methylome present allergen to T cells, and this effect is abrogated by an epigenetically acting drug in vitro.

Pediatric asthma is a common chronic airway inflammatory disease that begins in childhood and its impact persists throughout all age stages of patients. With the continuous progress of detection technologies, numerous studies have firmly demonstrated that gut microbiota and respiratory microbiota are closely related to the occurrence and development of asthma, and related research is increasing day by day. This article elaborates in detail on the characteristics, composition of normal gut microbiota and lung microbiota at different ages and in different sites, as well as the connection of the gut-lung axis. Subsequently, it deeply analyzes various factors influencing microbiota colonization, including host factor, delivery mode, maternal dietary and infant feeding patterns, environmental microbial exposure and pollutants, and the use of antibiotics in early life. These factors are highly likely to play a crucial role in the onset process and disease progression of asthma. Research shows that obvious changes have occurred in the respiratory and gut microbiota of asthma patients, and these microbiomes exhibit different characteristics according to the phenotypes and endotypes of asthma. Finally, the article summarizes the microbiota-related treatment approaches for asthma carried out in recent years, including the application of probiotics, nutritional interventions, and fecal microbiota transplantation. These treatment modalities are expected to become new directions for future asthma treatment and bring new hope for solving the problem of childhood asthma.

Apple pomace is a waste in fruit juice processing and is an important raw material for pectin extraction. The addition of pectinase will not only change the juice characteristics but also affect the apple pomace. However, the differences in the structure and function of pectin obtained from the pectinase-treated (TAPP) and untreated apple pomace (NTAPP) are unclear. In this paper, TAPP and NTAPP (APPs) were prepared using the subcritical-water method. Structural analysis showed that the APPs were acidic-pectin polysaccharides with low molecular weight (Mw) and a high esterification degree (DE), but TAPP had a lower Mw, DE, and galacturonic acid content and smoother surface. Immune activity detection demonstrated that NTAPP can stimulate macrophage proliferation, phagocytosis, and cytokine release by activating the TLR4/p-ERK/p-NFκB pathway, while TAPP activates the TLR4/p-NFκB to stimulate macrophage phagocytosis and the cytokine release. In vitro fermentation characteristics indicate that anaerobic fermentation using APPs as the sole carbon source can significantly promote the production of lactic acid and the short-chain fatty acids (SCFAs). Microbial diversity analysis revealed that the APPs exhibit prebiotic properties, but their effects on the gut microbiota composition differ: TAPP mainly promotes the enrichment of Akkermansia, while NTAPP primarily enhances the abundance of Faecalibaculum and Dubosiella. Finally, structure-function correlation analysis suggests that monosaccharide composition (particularly mannose) and molecular weight (Mw) are key factors influencing the gut microbiota composition, providing a research direction for future studies on their structure-activity relationships.

Early-life gut microbiota metabolites profoundly influence gut homeostasis, neurodevelopment, metabolic regulation, and immune system maturation. However, there is still a lack of comprehensive summaries and discussions regarding gut microbiota metabolites during early-life stages. This review systematically analyzes microbiota metabolites, including short-chain fatty acids, secondary bile acids, tryptophan metabolites, and branched-chain fatty acids, and delves into their production mechanisms and temporal dynamics. Additionally, the review highlights how maternal factors, breastfeeding, complementary feeding, and environmental influences shape the composition and metabolic functions of the early-life gut microbiota, emphasizing that early life is a crucial window for lifelong health interventions. By integrating the latest research findings and identifying knowledge gaps, this review emphasizes the molecular mechanisms of gut microbiota metabolites and their role in addressing common early-life diseases, including their potential as early biomarkers for screening, prevention, improvement, and even treatment of early diseases, as well as predicting their potential related diseases. On the basis of these insights, this review lays the foundation for future research and practical applications, aiming to promote optimal health from infancy to childhood.

Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate-to-severe atopic dermatitis (AD).

In this randomized, double-blind, placebo-controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate-to-severe adult patients with AD. All patients received FMT or placebo once a week for 3 weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial.

Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo-treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF-α, and total IgE in serum. By contrast, the expression levels of IL-12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4-dihydroxy-6-naphthoate biosynthesis II.

FMT was a safe and effective therapy in moderate-to-severe adult patients with AD; the treatment changed the gut microbiota compositions and functions.

Canine atopic dermatitis (cAD) is a chronic inflammatory disease that significantly reduces the quality of life in dogs. Dysbiosis of the gut microbiota affects skin diseases through the gut-skin axis. Therefore, microbiota-targeted therapy may potentially serve as a new management strategy for cAD. The present study aimed to investigate the association between gut microbiota and cAD and to evaluate the effect of probiotics on the clinical symptoms of cAD and gut microbiota in dogs.

Gut microbiota was analyzed at baseline and after 8 and 16 weeks. Baseline analysis revealed significantly lower (p < 0.05) gut microbial diversity in dogs with cAD than in healthy dogs. Differential abundance analysis showed that Fusobacterium, Megamonas, Collinsella, unclassified Clostridiales, Bacillus, Helicobacter, and Caproiciproducens were significantly more abundant in healthy dogs. In contrast, Clostridioides, Erysipelatoclostridium, Clostridium, Terrisporobacter, and unclassified Ruminococcaceae were significantly more abundant in dogs with cAD, In addition, differential abundance analysis showed that the abundance of 46 metabolic pathways were significantly different between healthy dogs and dogs with cAD indicating the dysbiosis of the gut microbiota in cAD. Moreover, the clinical severity of cAD was negatively correlated (p < 0.05) with alpha diversity and the abundance of Fusobacterium and Megamonas. Notably, daily probiotic administration for 16 weeks significantly decreased the clinical severity (p < 0.05). Dogs with good prognoses exhibited significantly increased alpha diversity, whereas those with poor prognoses did not, suggesting that the therapeutic effects of probiotics may be mediated by changes in gut microbial diversity.

This study highlights the association between gut microbiota dysbiosis and cAD in dogs and demonstrates that probiotic administration can effectively ameliorate cAD by improving gut microbial dysbiosis. These findings provide a basis for novel microbiota-based therapies in cAD treatment.

Infant food allergies have become a continually rising global health issue. There is a lack of global standardized recommendations on measures for prevention and treatment of infant food allergies because of the variations in ethnic, social, educational, and healthcare practices that affect the outcomes of research studies. Food allergies can cause mild to severe reactions and can affect social and emotional aspects of life up to the adolescent stage and are sometimes never outgrown. Maternal factors such as in utero supply of antibodies, dietary diversity, genetics, food allergen consumption during pregnancy, gut microbiota, and breastfeeding characteristics are the cornerstones of the development of an infant's immune system. In this review, we discuss how prenatal and postnatal factors affect the gut microbiota and development of an infant's immune system, and the current therapies available. The importance of food processing and education of stakeholders in the care of infants with food allergies is also discussed.

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

Cold argon plasma (CAP) effectively modifies casein (CN) structures by cleaving peptide chains and altering allergenic epitopes. This study assessed the allergenicity of CAP-treated CN in KU812 cells and BALB/c mouse models, supported by a multiomics approach integrating 16S rDNA sequencing, serum metabolomics, and jejunal transcriptomics. CAP treatment reduced CN allergenicity, evidenced by decreased KU812 cell degranulation, alleviated allergic responses in mice, and a Th1/Th2 balance shift toward Th1 dominance. Furthermore, CAP-treated CN restored the gut microbiota equilibrium, increasing the number of beneficial bacteria. Multiomics analysis highlighted its impact on lipid metabolism pathways, with Zbp1 and Hbb-bt identified as potential regulators of allergic responses. These findings underscore the potential of cold argon plasma as an innovative strategy to reduce food allergenicity through multifaceted physiological mechanisms, offering promising therapeutic applications in food allergy management.

Propionate, a short-chain fatty acid (SCFA), has recently attracted attention for its various health benefits. However, elevated levels of propionate in certain pathological conditions can have adverse effects. Propionic acidemia (PA) is a rare metabolic disorder caused by mutations in the propionyl-CoA carboxylase (PCC) gene (PCCA or PCCB), leading to reduced PCC activity and impaired propionyl-CoA metabolism. This metabolic block at the PCC-mediated step results in the accumulation of propionyl-CoA and its metabolites, including propionate, contributing to various complications, such as neurological dysfunction, in patients with PA. This review examines propionate synthesis, its physiological role, its metabolism in healthy individuals and those with PA, and the pathological link between elevated propionate levels and neurological dysfunctions in PA patients. A deeper understanding of propionate metabolism under both normal and pathological conditions will help clarify the full spectrum of its metabolic effects.

Food allergies are increasing globally, particularly in Asia; however, the etiologies of allergic diseases remain poorly understood despite comprehensive studies conducted across a variety of populations. Epidemiological research demonstrates that food allergy is more prevalent in Westernized or urbanized societies than in rural or developing ones. As such, comparing the distribution and patterns of food allergies as well as the environmental exposures between regions may provide insight into potential causal and protective factors of food allergy. Diet is an important exposome that has been shown to modulate the immune system both directly and indirectly via pathways involving the microbiota. Changes in dietary patterns, especially the shift to a Westernized diet with reduced dietary fiber and an abundance of processed foods, impact the gut and skin epithelial barrier and contribute to the development of chronic inflammatory diseases, such as food allergy. Although dietary intervention is believed to have tremendous potential as a strategy to promote immunological health, it is essential to recognize that diet is only one of many factors that have changed in urbanized societies. Other factors, such as pollution, microplastics, the use of medications like antibiotics, and exposure to biodiversity and animals, may also play significant roles, and further research is needed to determine which exposures are most critical for the development of food allergies.

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

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

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

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

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

Childhood is a multifactorial disease, and recent research highlights the influence of early-life microbial communities in shaping disease risk. This review explores the roles of the gut and respiratory microbiota in asthma development, emphasizing the importance of early microbial exposure. The gut microbiota has been particularly well studied, with certain taxa like Faecalibacterium and Bifidobacterium linked to asthma protection, whereas short-chain fatty acids produced by gut microbes support immune tolerance through the gut-lung axis. In contrast, the respiratory microbiota, though low in biomass, shows consistent associations between early bacterial colonization by Streptococcus, Moraxella, and Haemophilus and increased asthma risk. The review also addresses the emerging roles of the skin microbiota and environmental fungi in asthma, though findings remain inconsistent. Timing is a critical factor, with early-life disruptions, such as antibiotic use, potentially leading to increased asthma risk. Despite significant advances, there are still unresolved questions about the long-term consequences of early microbial perturbations, particularly regarding whether microbial dysbiosis is a cause or consequence of asthma. This review integrates current findings, highlighting the need for deeper investigation into cross-organ interactions and early microbial exposures to understand childhood asthma pathophysiology.

There is a growing acknowledgment of the gut microbiome's impact on widespread immune responses, which holds considerable importance for comprehending and addressing asthma. Recent research has clarified the complex interactions between gut microbiota and airway immune systems, demonstrating that microbial diversity and composition can affect both the initiation and advancement of asthma. Gut microbial species and metabolites primarily short-chain fatty acids (SCFAs) may either worsen or reduce airway inflammation by regulating the balance of helper T cell 1 (Th1) / helper T cell 2 (Th2) and other immune mediators. This interaction presents innovative therapeutic possibilities, including modulation of gut microbiome during early life through breastfeeding and control of antibiotic use, particularly with prebiotics, which could selectively stimulate the growth of beneficial bacteria, promote immune maturation, reducing susceptibility to asthma and allergic airway inflammation. Besides, investigating the gut-lung axis reveals new opportunities for personalized medicine in asthma treatment, emphasizing the necessity for integrated strategies that take individual microbiome profiles into account. This paper examines the latest developments in comprehending the mechanisms by which gut microbiota affect airway inflammation and hypersensitivity, especially focusing on treatment strategies.

An estimated 10% of COVID-19 survivors have been reported to suffer from complaints after at least three months. The intestinal microbiome has been shown to impact long COVID through the gut-lung axis and impact the severity. We aimed to investigate the relationship between the gut microbiome and clinical characteristics, exploring microbiome heterogeneity through clustering. Seventy-nine patients with long COVID evaluated at 3 to 6 months after infection were sampled for fecal metagenome analysis. Patients were divided into two distinct hierarchical clusters, based solely on the microbiome composition. Compared to cluster 1 (n = 67), patients in cluster 2 (n = 12) showed a significantly reduced lung function (FEV1, FVC, and DLCO) and during acute COVID-19 showed a longer duration of hospital admissions (48 compared to 7 days) and higher rates of ICU admissions (92% compared to 22%). Additionally, the microbiome composition showed a reduced alpha diversity and lower proportion of butyrate-producing bacteria in cluster 2 together with higher abundances of Ruminococcus gnavus, Escherichia coli, Veillonella spp. and Streptococcus spp. and reduced abundances of Faecalibacterium prausnitzii and Eubacteria spp. Further research could explore the effect of pre- and pro-biotic supplementation and its impact on lung function and societal participation in long COVID.

Epidemiological studies indicate a rising prevalence of allergic diseases, now recognized as a major global public health concern. In children, the progression of these diseases often follows the "atopic march," beginning with eczema, followed by food allergies, allergic rhinitis, and asthma. Recent research has linked gut microbiota dysbiosis to the development of allergic diseases in children. The gut microbiota, a crucial component of human health, plays a vital role in maintaining overall well-being, highlighting its potential in preventing and modifying the course of allergic diseases. This review examines the relationship between childhood allergic diseases and gut microbiota, drawing on the latest evidence. We first elaborated the concepts of allergic diseases and gut microbiota, followed by a discussion of the developmental trajectory of the gut microbiota in healthy children. This review further explored the richness, diversity, and composition of the gut microbiota, as well as specific microbial taxa associated with allergic disease. Lastly, we discussed the current status and future potential of probiotic interventions in managing pediatric allergic diseases.

The prebiotic properties of human milk oligosaccharides (HMOs) and emerging evidence of immunomodulatory effects suggest their potential therapeutic value in allergy management. 2'-Fucosyllactose (2'-FL) has been reported to alleviate food allergies, while the effect of other fucosylated HMOs on food allergy remains unclear. In this study, we assess the effect of two HMOs, 2'-FL and 3-fucosyllactose (3-FL), on symptomatology and immunological responses in an ovalbumin (OVA)-sensitized mouse model of food allergy as well as their influence on gut microbiota. The assessment of allergic symptoms, specific immunoglobulin E (IgE), and related gene expression levels in sensitized mice indicated that 3-FL was as effective as 2'-FL in alleviating food allergy. 2'-FL and 3-FL significantly decreased serum levels of OVA-specific IgE, mouse mast cell protease (mMCP-1) and IL-4 while increasing the levels of IFN-γ. Additionally, 2'-FL and 3-FL down-regulated gene expression of allergy-related cytokines in the small intestine and improved intestinal barrier damage. Furthermore, both 2'-FL and 3-FL treatment positively influenced the gut microbial profiles, in particular by enhancing the proportion of beneficial bacteria such as Lactobacillus and Bifidobacterium and decreasing the percentage of Turicibacter and Lachnospiraceae NK4A136 group, thereby modulating the immune system. Therefore, this study can provide insights into 2'-FL and 3-FL to alleviate OVA-induced allergy.

Type 2 innate lymphoid cells (ILC2s) are essential for maintaining immune regulation and promoting tissue homeostasis in allergic asthma. How the development of gut microbiota on neonatal ILC2s influences allergic airway inflammation remains unclear. Here we focus on offspring ILC2 development in the context of alterations in maternal gut microbiota.

C57BL/6 maternal mice were gavaged with OM-85 during pregnancy and/or lactation, ILC2-driven allergic airway inflammation in the OVA-sensitized adult offspring was observed. ILC2 development in offspring early life were investigated using recombinant (r)IL-33, rIL-25 and Bromodeoxyuridine in the vivo experiments. Further ILC2 promoting factors- IL-33 and IL-25 production in offspring early life were analysed. Finally, we examined the changes in gut microbiota and its metabolites in both dams and pups, and explored the effects of short-chain fatty acids (SCFAs) on IL-33 expression and secretion.

Maternal OM-85 administration restrained ILC2-driven allergic airway inflammation in the OVA-sensitized adult offspring. During ILC2 development in offspring early life, maternal OM-85 administration suppressed IL-33 and IL-25 production to inhibit ILC2 expansion and ILC2 responsiveness to alarmins, and infantile ILC2s could persist into adulthood. Maternal OM-85 administration increased SCFAs in breast milk and SCFA-producing gut probiotics (predominant Bacteroides and Blautia) in offspring, especially during pregnancy and lactation. SCFAs down-regulated IL-33 expression and reduced IL-33 secretion by inhibited gasdermin D (GSDMD) formation.

Maternal OM-85 administration restrains ILC2-driven allergic airway inflammation in adult offspring by increasing offspring intestinal SCFAs to modulate ILC2 development at an early stage, demonstrating that the transgenerational effects of maternal OM-85 exposure on offspring innate immunity.

We explored the effects of two formulas, extensively hydrolyzed formula (EHF) and amino acid-based formula (AAF), on the gut microbiota and short-chain fatty acids (SCFAs) in infants with food protein-induced enterocolitis syndrome (FPIES).

Fecal samples of thirty infants with bloody diarrhea receiving EHF or AAF feeding were collected at enrollment, diagnosis of FPIES, and four weeks after diagnosis. The gut microbiota and SCFAs were analyzed using 16 S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively.

Microbial diversity of FPIES infants was significantly different from that of the controls. FPIES infants had a significantly lower abundance of Bifidobacterium and a higher level of hexanoic acid compared with controls. In EHF-fed FPIES infants, microbial richness was significantly decreased over time; while the microbial diversity and richness in AAF-fed FPIES infants exhibited no differences at the three time points. By four weeks after diagnosis, EHF-fed FPIES infants contained a decreased abundance of Acinetobacter, whereas AAF-fed FPIES infants contained an increased abundance of Escherichia-Shigella. EHF-fed infants experienced significantly decreased levels of butyric acid and hexanoic acid at four weeks after diagnosis.

Infants with FPIES had intestinal dysbiosis and different formulas differentially affected gut microbiota and SCFAs in FPIES infants.

We firstly report the impacts of two different nutritional milk formulas on the gut microbial composition and SCFAs levels in infants with FPIES. We show that infants with FPIES have obvious intestinal dysbiosis and different formulas differentially affect gut microbiota and SCFAs in FPIES infants. Understanding the effects of different types of formulas on gut microbial colonization and composition, as well as the related metabolites in infants with FPIES could help provide valuable insights for making choices about feeding practices.

The intestinal microbiota is a complex community of organisms present in the human gastrointestinal tract, some of which can produce short-chain fatty acids (SCFAs) through the fermentation of dietary fiber. SCFAs play a major role in mediating the intestinal microbiota's regulation of host immunity and intestinal homeostasis. Respiratory syncytial virus (RSV) can cause an imbalance between anti-inflammatory and proinflammatory responses in the host. In addition, changes in SCFA levels and the structure of the intestinal microbiota have been observed after RSV infection. Therefore, there may be a link between SCFAs and RSV infection, and SCFAs are expected to be therapeutic targets for RSV infection.

Perinatal nicotine exposure (PNE) induces pulmonary dysplasia in offspring and it increases the risk of respiratory diseases both in offspring and across generations. The maternal gut microbiota and its metabolites, such as short-chain fatty acids (SCFAs), can regulate fetal lung development and are susceptible to nicotine exposure. Therefore, modulation of PNE-induced changes in maternal gut microbiota and SCFAs may prevent the occurrence of pulmonary dysplasia in offspring.

Our previous studies demonstrated that electroacupuncture (EA) ameliorated PNE-induced impairment in offspring lung development. To further our study, we aimed to determine whether the protective effect of EA is associated with the modulation of changes in maternal gut microbiota and SCFAs.

We observed changes in maternal gut microbiota and serum SCFA levels in both mother and offspring after EA treatment using a PNE rat model. Furthermore, using broad-spectrum antibiotics, we established a pseudo-germ-free PNE rat model to explore whether EA can protect offspring's pulmonary function and lung morphology in the presence of depleted maternal gut microbiota.

Our study revealed that EA increased the community richness (Sobs index) of perinatal nicotine-exposed maternal gut microbiota and the abundance of beneficial bacteria (RF39, Clostridia, Oscillospirales, etc.). This was accompanied by an upregulated serum levels of acetate, butyrate, and total SCFAs in both mother and offspring rats, as well as stimulated expression of SCFA receptors (GPR41 and GPR43) in the lung tissue of offspring rats. However, the beneficial effects of EA on offspring pulmonary function (FVC, PEF, PIF, and Cdyn) and lung morphology (alveolar number and MLI) were lost after maternal gut microbiota depletion.

These findings suggest that EA may exert its therapeutic effects on PNE-induced lung phenotype by altering maternal gut microbiota. The likely mechanism involves the associated improvement in serum SCFA levels in both mother and offspring, as well as the upregulation of SCFA receptors in the lung tissue of offspring.

Many studies reported the influence of infants' gut microbiota on atopic dermatitis (AD) postnatally, yet the role of maternal gut microbiota and plasma metabolites in infants' AD remains largely unexplored.

Sixty-three pregnant mother-infants were enrolled and followed after childbirth in Guangzhou, China. Demographic information, maternal stool and plasma samples, and records for infants' AD were collected. Maternal gut microbiota/metabolome and plasma metabolome were profiled using shotgun metagenomics and non-targeted metabolomics. Logistic regression and multi-omics analysis were used to explore characteristic maternal gut microbiota in the AD and health groups.

The α-diversity of maternal gut microbiota in health group was significantly higher than AD group (Shannon diversity P = 0.02, Simpson diversity P = 0.04). Short-chain fatty acids (SCFAs) producing microorganisms, including Faecalibacterium, Roseburia, Butyricicoccus, and Ruminococcus, as well as the abundance of phenylalanine, tyrosine, and tryptophan biosynthesis pathway, were enriched in health group (LDA>2 and P < 0.05). Virulent factors (VFs) involved in immune modulation were enriched in the health group, while VFs involving in adhesin were enriched in the AD group (P < 0.05). Metabolomic analysis showed that a polyunsaturated fatty acid/linoleic acid, 13S-hydroxyoctadecadienoic, were negatively associated with AD in both the gut and plasma samples (FDR<0.05). Several other linoleic acids and flavonoids were negatively associated with AD (FDR<0.05). Neural network analysis revealed that microorganisms enriched in health group may produce these protective fatty acids.

Our findings show that maternal gut microorganisms/metabolites and plasma metabolites during pregnancy impact subsequent pathogenesis of infants AD. This illuminates new strategies against early AD in offspring.

Food allergies, particularly peanut (PN) allergies, are a growing concern, with fatal anaphylaxis incidents often reported. While palforzia is the sole FDA-approved drug for managing PN allergies, it is not universally effective.

This study aimed to investigate the potential of Gynostemma pentaphyllum saponins (GpS) as a novel therapeutic agent for PN allergy through modulation of gut microbiota, addressing the limitations of current treatments.

To elucidate the role of GpS on peanut allergy, we first built a PN-sensitized C57BL/6J model mice. Through comprehensive sequencing analysis, we identified Parabacteroides distasonis as a key bacterium triggering PN sensitization. Employing the same mouse model, GpS was evaluated for its effects on anaphylactic symptoms, serum immunoglobulin levels, and allergy-related biomarkers. 16S rRNA sequencing and transcriptomic analysis were applied to investigate the impact of GpS on the host's gut epithelium and microbiome.

GpS treatment effectively reduced anaphylactic symptoms in PN-sensitized mice, as shown by decreased IgG1, total IgE, and PN-specific IgE levels. It also modulated the immune response by suppressing proinflammatory cytokines (IL-1β, IFN-γ, IL-21) and chemokines (CCL5, CCL12, CCL17, CCL22), while enhancing anti-inflammatory cytokines (IL-4, IL-10, IL-12, IL-13). Fecal microbial transplant from GpS-treated Model mice to PN-sensitized mice displayed anti-peanut allergy effects. Additionally, the administration of GpS-enhanced bacteria (Clostridium aldenese or Lactobacillus murinus), alleviated anaphylactic symptoms and reduced serum allergy markers in PN-sensitized mice.

To conclude, we revealed the intestinal environment, signaling molecules, mucosal cytokines, and commensal microbial profiles in the peanut-sensitized mouse model. We further presented evidence for the protective effect of GpS against PN allergen sensitization by downregulating a series of food-allergy-associated biomarkers and cytokines via the modulation of gut bacteria. More importantly, supported by both in vitro and in vivo experiments, we demonstrated that the protective effect of GpS against PN-allergy is through the enhancement of two commensal bacteria, Clostridium aldenese, and Lactobacillus murinus.

Studies of childhood diet diversity and allergic disease have not examined additional associations with an offspring allergy-linked maternal diet index during pregnancy. We studied both associations in a pre-birth cohort.

Offspring allergic disease diagnoses were obtained from electronic medical records. Maternal and infant diet were self-reported. Adjusted parametric Weibull time-to-event models assessed associations between maternal diet index, infant diet diversity and time to development of allergic rhinitis, atopic dermatitis, asthma, wheeze, IgE-mediated food allergy, and a combined outcome of any allergic disease except for wheeze.

Infant diet diversity at 1 year was associated with the risk of the combined outcome between 1 and 4 years of age (p = .002). While both maternal diet index and infant diet diversity at 1 year were associated with the risk of the combined outcome between 1 and 4 years of age (both p < .05), infant diet diversity at 1 year did not modify the association between maternal diet index and the risk of the combined outcome between 1 and 4 years of age (p = .5). The group with the lowest risk of the combined allergy outcome had higher maternal diet index and higher infant diet diversity.

The novel finding that both maternal diet index during pregnancy and infant diet diversity at 12 months are associated with the risk of a combined allergic disease outcome points to two targets for preventive interventions: maternal diet index scores during pregnancy and offspring diet diversity during infancy.

Allergies are among the top causes of chronic disease in children. Their pathogenesis classically involves T helper 2 (Th2)-type inflammation driven by IgE-mediated allergen sensing. Triggers influencing allergic disease occur early in life, including before birth. The immature fetal immune system and mucosal barriers undergo periods of plasticity that are open to longitudinal programming by maternal influence. Evidence supports the importance of the maternal immune system in shaping perinatal immunity, as the transfer of cytokines, antibodies, and cells promotes offspring protection from pathogens. However, the same components may lead to allergic predisposition. Maternal-fetal interactions are further modified by epigenetic, metabolic, dietary, and microbiome-mediated effects. Here, we review how diverse maternal exposures and mediators signal across the placenta and through nursing perinatally to promote future tolerance or enhance reactivity against allergens. Improved understanding of the mechanisms predisposing for allergic disease in early life can guide the development of new therapeutics and preventative lifestyle modifications.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.

Over the past decades, the prevalence of allergic diseases noticeably increased in industrialized countries. The Th2 immune response plays a central role in these pathologies and its modulation using pro-/postbiotics constitutes a promising approach to prevent or alleviate disease symptoms. The aim of this in vitro study, was to investigate the ability of human milk-derived Bifidobacterium breve DSM 32583 (Bb) and Limosilactobacillus fermentum CECT5716 (Lf), to modulate the Th2 induced responses. To this end, Th2 cells were generated by co-culturing of human naïve Th cells with monocyte-derived dendritic cells (moDCs) either stimulated with Staphylococcus aureus or IL-33. The immunomodulatory effects of pro-/postbiotic preparations of Bb and Lf on moDCs and Th2 cells were evaluated in terms of maturation markers expression and cytokines production. Remarkably, the tested strains induced the anti-inflammatory cytokine IL-10 in moDCs, in a strain-, dose- and viability-dependent manner with no significant upregulation of IL-12p70 nor CD83, CD86 or HLA-DR. Interestingly, Bb and Lf postbiotics were able to dampen the Th2/Th1 response induced upon S. aureus- or IL-33 stimulation. They were also able to synergistically induce IL-10 in moDCs and T cells, upon co-stimulation with LPS. Finally, we observed that live probiotics triggered a mild Th1 response that was attenuated in the presence of galacto-oligosaccharides. Altogether, Bb and Lf pro-/postbiotics exhibited remarkable immune regulatory effects on both moDCs and Th2 cells. Therefore, further in vivo studies should be considered to validate these findings and assess their ability to prevent allergy or alleviate its symptoms in affected patients.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with multifactorial and unclear pathogenesis. Its development is characterized by two key elements: epigenetic dysregulation of molecular pathways involved in AD pathogenesis and disrupted skin and gut microbiota (dysbiosis) that jointly trigger and maintain chronic inflammation, a core AD characteristic. Current data suggest that failed inflammation resolution is the main pathogenic mechanism underlying AD development. Inflammation resolution is provided by specialized pro-resolving mediators (SPMs) derived from dietary polyunsaturated fatty acids acting through cognate receptors. SPM levels are reduced in AD patients. Administration of SPMs or their stable, small-molecule mimetics and receptor agonists, as well as supplementation with probiotics/prebiotics, demonstrate beneficial effects in AD animal models. Epidrugs, compounds capable of restoring disrupted epigenetic mechanisms associated with the disease, improve impaired skin barrier function in AD models. Based on these findings, we propose a novel, multilevel AD treatment strategy aimed at resolving chronic inflammation by application of SPM mimetics and receptor agonists, probiotics/prebiotics, and epi-drugs. This approach can be used in conjunction with current AD therapy, resulting in AD alleviation.

At the beginning of the COVID-19 pandemic, people had to stay at home due to quarantine, and the food delivery industry grew significantly. Concerns have been raised regarding the popularity of away-from-home (AFH) meals and their impact on health. In this study, we evaluated the association between the frequency of AFH meals and the prevalence of allergic rhinitis (AR) and chronic rhinosinusitis (CRS). In this cross-sectional study, the Korean National Health and Nutrition Examination Survey was reviewed from 2010 to 2019. The frequency of AFH meals was assessed as how often the respondents ate AFH meals in an average week. Those who ate AFH meals less than once per week were designated as group 1, one to four times as group 2, and five times or more as group 3. The diagnoses of AR and CRS were evaluated, and symptoms, endoscopic findings, and serum immunoglobulin E (IgE) levels were assessed. Logistic regression analyses were performed. A total of 48,515 participants were eligible. In multivariate logistic regression analysis for AR, when compared to group 1, the odds ratios (ORs) for AR in participants of group 2 (OR = 1.226, 95% confidence interval [CI] = 1.136-1.324) and group 3 (OR = 1.227, 95% CI = 1.126-1.337) were significantly higher (p < 0.0001). For CRS, group 2 (OR = 1.139, 95% CI = 1.029-1.260) and group 3 (OR = 1.210, 95% CI = 1.078-1.358) showed a significantly higher risk than group 1 (p = 0.0044). Individuals who consume AFH meals frequently might suffer less from AR or CRS if they change their dietary habits and prepare meals more often at home.

The microbes, nutrients and toxins that we are exposed to can have a profound effect on the composition and function of the gut microbiome. Thousands of peer-reviewed publications link microbiome composition and function to health from the moment of birth, right through to centenarians, generating a tantalizing glimpse of what might be possible if we could intervene rationally. Nevertheless, there remain relatively few real-world examples where successful microbiome engineering leads to beneficial health effects. Here we aim to provide a framework for the progress needed to turn gut microbiome engineering from a trial-and-error approach to a rational medical intervention. The workflow starts with truly understanding and accurately diagnosing the problems that we are trying to fix, before moving on to developing technologies that can achieve the desired changes.

Moderate-late preterm-born infants experience more frequent and severe respiratory tract infections and wheezing compared to term-born infants. Decreasing the risk on respiratory tract infections and wheezing in this group is vital to improve quality of life and reduce medical consumption during infancy, but also to reduce the risk on asthma and COPD later in life. Until now, moderate-late preterm infants are underrepresented in research and mechanisms underlying their morbidity are largely unknown, although they represent 80% of all preterm-born infants. In order to protect these infants effectively, it is essential to understand the role of the immune system in early life respiratory health and to identify strategies to optimize immune development and respiratory health. This review elaborates on risk factors and preventative measures concerning respiratory tract infections and wheezing in preterm-born infants, exploring their impact on the immune system and microbiome. Factors discussed are early life antibiotic use, birth mode, feeding type and living environment. Further, differences in adaptive and innate immune maturation between term and preterm infants are discussed, as well as differences in local immune reactions in the lungs. Finally, preventative strategies are being explored, including microbiota transplantation, immune modulation (through pre-, pro-, syn- and postbiotics, bacterial lysates, vaccinations, and monoclonal antibodies) and antibiotic prophylaxis.

Epigenetic modifications control gene expression and are essential for turning genes on and off to regulate and maintain differentiated cell types. Epigenetics are also modified by a multitude of environmental exposures, including diet and pollutants, allowing an individual's environment to influence gene expression and resultant phenotypes and clinical outcomes. These epigenetic modifications due to gene-environment interactions can also be transmitted across generations, raising the possibility that environmental influences that occurred in one generation may be transmitted beyond the second generation, exerting a long-lasting effect. In this review, we cover the known mechanisms of epigenetic modification acquisition, reprogramming and persistence, animal models and human studies used to understand multigenerational epigenetic transmission, and examples of environmentally induced epigenetic change and its transmission across generations. We highlight the importance of environmental health not only on the current population but also on future generations that will experience health outcomes transmitted through epigenetic inheritance.

The infant gut microbiota undergoes significant changes during early life, which are essential for immune system maturation, nutrient absorption, and metabolic programming. Among the various microbial metabolites, short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, produced through the fermentation of dietary fibers by gut bacteria, have emerged as critical modulators of host-microbiota interactions. SCFAs serve as energy sources for colonic cells and play pivotal roles in regulating immune responses, maintaining gut barrier integrity, and influencing systemic metabolic pathways. Recent research highlights the potential neuroprotective effects of SCFAs in pediatric populations. Disruptions in gut microbiota composition and SCFA production are increasingly associated with a range of pediatric health issues, including obesity, allergic disorders, inflammatory bowel disease (IBD), and neurodevelopmental disorders. This review synthesizes current knowledge on the role of microbiota-derived SCFAs in pediatric health, emphasizing their contributions from gut development to neuroprotection. It also underscores the need for further research to unravel the precise mechanisms by which SCFAs influence pediatric health and to develop targeted interventions that leverage SCFAs for therapeutic benefits.