Limited research exists on the link between antibiotic use and emotion and behavior, particularly the lack of continuous emotional and behavioral assessment. Emotions and behaviors reflect key modifiable dimensions of brain function and evolve during childhood growth and development. This paper aimed to examine the antibiotic use (yes/no), categories and duration in association with preschool children's emotional and behavioral development trajectory.

Based on Ma'anshan-Anhui Birth Cohort, 1147 mother-child pairs were included in the study. Parents or guardians reported the children's antibiotic use before age 3, including whether antibiotics were used and the types and duration of antibiotics use. The trajectories of children's emotional and behavioral development were fitted using scores from the Strengths and Difficulties Questionnaire (SDQ) at 48, 60, and 72 months.

A total of 23.3 % (268/1147) of children had used antibiotics in the past three months. Children's antibiotic use significantly related with high level of hyperactivity. The use of β-lactam antibiotics, especially non-penicillin, was associated with the risk of high level hyperactivity at a dose-response pattern in duration. Children's combined use of β-lactam and macrolides was related with increased risk of high level hyperactivity, total difficulties and emotional symptoms.

Children's antibiotic use before age 3 is observed to be associated with hyperactivity development, especially using β-lactam antibiotics with a relatively long duration. The combined use of β-lactam and macrolides may increase the development of hyperactivity, total difficulties and emotional symptoms.

Dysbiosis refers to the disruption of the gut microbiota balance and is the pathological basis of various diseases. The main pathogenic mechanisms include impaired intestinal mucosal barrier function, inflammation activation, immune dysregulation, and metabolic abnormalities. These mechanisms involve dysfunctions in the gut-brain axis, gut-liver axis, and others to cause broader effects. Although the association between diseases caused by dysbiosis has been extensively studied, many questions remain regarding the specific pathogenic mechanisms and treatment strategies. This review begins by examining the causes of gut microbiota dysbiosis and summarizes the potential mechanisms of representative diseases caused by microbiota imbalance. It integrates clinical evidence to explore preventive and therapeutic strategies targeting gut microbiota dysregulation, emphasizing the importance of understanding gut microbiota dysbiosis. Finally, we summarized the development of artificial intelligence (AI) in the gut microbiota research and suggested that it will play a critical role in future studies on gut dysbiosis. The research combining multiomics technologies and AI will further uncover the complex mechanisms of gut microbiota dysbiosis. It will drive the development of personalized treatment strategies.

Microplastics (MPs) and antibiotic tetracycline (TC) are widespread in the environment and constitute emerging combined contaminants. Young individuals are particularly vulnerable to agents that disrupt intestinal health and development. However, the combined effects of MPs and TC remain poorly understood. In this study, we developed a young mouse model exposed to polystyrene MPs, either alone or in combination with TC for 8 weeks to simulate real-life dietary exposure during early life. Our findings revealed that concurrent exposure to MPs and TC caused the most severe intestinal barrier dysfunction driven by inflammatory activation and oxidative imbalance. Moreover, exposure to MPs and TC reduced the abundance of potential probiotics while promoting the growth of opportunistic pathogens. Metagenomic analysis further indicated that co-exposure to MPs and TC enhanced the abundance of bacteria carrying either antibiotic resistance genes (ARGs) or virulence factor genes (VFGs), contributing to the widespread dissemination of potentially harmful genes. Finally, a strong positive correlation was observed between microbiota dysbiosis, ARGs, and VFGs. In general, this study highlighted the hazards of MPs and antibiotics to intestinal health in young mice, which provided a new perspective into the dynamics of pathogens, ARGs, and VFGs in early-life intestinal environments.

Environmental factors like diet and antibiotics modulate the gut microbiota in early life. During weaning, gut microbiota progressively diversifies through exposure to non-digestible carbohydrates (NDCs) from diet, while antibiotic perturbations might disrupt this process. Supplementing an infant's diet with prebiotic NDCs may mitigate the adverse effects of antibiotics on gut microbiota development. This study evaluated the influence of supplementation with 2-fucosyllactose (2'-FL), galacto-oligosaccharides (GOS), or isomalto/malto-polysaccharides containing 87% of α(1→6) linkages (IMMP-87), on the recovery of antibiotic-perturbed microbiota. The TIM-2 in vitro colon model inoculated with fecal microbiota of 9-month-old infants was used to simulate the colon of weaning infants exposed to the antibiotics amoxicillin/clavulanate or azithromycin. Both antibiotics induced changes in microbiota composition, with no signs of recovery in azithromycin-treated microbiota within 72 h. Moreover, antibiotic exposure affected microbiota activity, indicated by a low valerate production, and azithromycin treatment was associated with increased succinate production. The IMMP-87 supplementation promoted the compositional recovery of amoxicillin/clavulanate-perturbed microbiota, associated with the recovery of Ruminococcus, Ruminococcus gauvreauii group, and Holdemanella. NDC supplementation did not influence compositional recovery of azithromycin-treated microbiota. Irrespective of antibiotic exposure, supplementation with 2'-FL, GOS, or IMMP-87 enhanced microbiota activity by increasing short-chain fatty acids production (acetate, propionate, and butyrate).

Cardiovascular diseases (CVDs) remain the major cause of morbidity and mortality amongst people of all ages across the world. Research suggests that the initiation and progression of CVDs are associated with antibiotic-induced gut dysbiosis. Antibiotics are primarily intended to be used to treat bacterial infections, which can alter gut microbiota (GM) composition, by lowering the abundance of beneficial bacteria, like Firmicutes, Bacteroidetes, and increasing the profusion of Enterobacteriaceae, leading to harm on gut health. Additionally, it reduces short-chain fatty acids (SCFAs) and bile acid metabolism, increases trimethylamine N-oxide (TMAO) production, intestinal permeability allowing lipopolysaccharide (LPS) and TMAO into systemic circulation. SCFAs play a key role in lipid metabolism, inflammation, and strengthening of the intestinal barrier, and participate in CVDs through FFAR2 and FFAR3 receptors, whereas dysbiosis reduces SCFAs levels and worsens these effects. TMAO enhances oxidative stress, inflammation, endothelial dysfunction, and cholesterol dysregulation, thus worsening CVDs. Furthermore, LPS develops systemic inflammation, insulin resistance, and endothelial dysfunction by activating the NF-κB pathway. Dysbiosis also affects bile acid synthesis, disrupting lipid and glucose metabolism, further participating in the progression of CVDs. This article aims to explore the role of gut dysbiosis in various CVDs, including congenital heart disease, hypertension, valvular heart disease, coronary heart disease, and heart failure. Furthermore, this article aims to bridge the knowledge gap regarding the gut-heart axis by exploring how antibiotics alter the gut microbiota homeostasis, further contributing to the development of CVDs and therapeutic interventions that reduce cardiovascular risks and restore the gut microbiota homeostasis.

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

In the fight against bacterial infections, particularly those caused by multi-resistant pathogens known as "superbugs", the need for new antibacterials is undoubted in scientific communities and is by now also widely perceived by the general population. However, the antibacterial research landscape has changed considerably over the past years. With few exceptions, the majority of big pharma companies has left the field and thus, the decline in R&D on antibacterials severely impacts the drug pipeline. In recent years, antibacterial research has increasingly relied on smaller companies or academic research institutions, which mostly have only limited financial resources, to carry a drug discovery and development process from the beginning and through to the beginning of clinical phases. This review formulates the requirements for an antibacterial in regard of targeted pathogens, resistance mechanisms and drug discovery. Strategies are shown for the discovery of new antibacterial structures originating from natural sources, by chemical synthesis and more recently from artificial intelligence approaches. This is complemented by principles for the computer-aided design of antibacterials and the refinement of a lead structure. The second part of the article comprises a compilation of antibacterial molecules classified according to bacterial target structures, e.g. cell wall synthesis, protein synthesis, as well as more recently emerging target classes, e.g. fatty acid synthesis, proteases and membrane proteins. Aspects of the origin, the antibacterial spectrum, resistance and the current development status of the presented drug molecules are highlighted.

Compelling evidence supports a link between early-life gut microbiota and the metabolic outcomes in later life. Using an early-life antibiotic exposure model in BALB/c mice, we investigated the life-course impact of prenatal and/or postnatal antibiotic exposures on the gut microbiome of offspring and the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Compared to prenatal antibiotic exposure alone, postnatal antibiotic exposure more profoundly affected gut microbiota development and succession, which led to aggravated endotoxemia and metabolic dysfunctions. This was primarily resulted from the overblooming of gut Parabacteroides and hepatic accumulation of cytotoxic lysophosphatidyl cholines (LPCs), which acted in conjunction with LPS derived from Parabacteroides distasonis (LPS_PA) to induce cholesterol metabolic dysregulations, endoplasmic reticulum (ER) stress and apoptosis. Integrated serum metabolomics, hepatic lipidomics and transcriptomics revealed enhanced glycerophospholipid hydrolysis and LPC production in association with the upregulation of PLA2G10, the gene controlling the expression of the group X secretory Phospholipase A2s (sPLA2-X). Taken together, our results show microbial modulations on the systemic MASLD pathogenesis and hepatocellular lipotoxicity pathways following early-life antibiotic exposure, hence help inform refined clinical practices to avoid any prolonged maternal antibiotic administration in early life and potential gut microbiota-targeted intervention strategies.

Background: Obesity contributes to cardiometabolic risk, including subclinical atherosclerosis and insulin resistance. This study examines the predictive roles of trimethylamine N-oxide (TMAO) and resistin in relation to carotid intima-media thickness and metabolic parameters; Methods: Sixty adults (18-71 years) with varying body weights were assessed for body composition, subclinical atherosclerosis, and blood biomarkers, including TMAO and resistin; Results: TMAO correlated strongly with CIMT (r = 0.674, p < 0.001), indicating its role in subclinical atherosclerosis. Logistic regression identified TMAO (threshold 380; AUC = 0.880, accuracy = 91.7%) as a predictor of cardiometabolic risk. Resistin was associated with CIMT, WHR, and total cholesterol, inversely linked to LDL cholesterol (p = 0.003). Less active participants exhibited higher TMAO (p = 0.001) and resistin (p = 0.02). Family histories of obesity and diabetes correlated with elevated TMAO, while resistin linked to shorter sleep duration and diabetes history, highlighting their importance in obesity-related cardiometabolic risks; Conclusions: TMAO is strongly linked to abdominal fat, insulin resistance, and subclinical atherosclerosis, while resistin is associated with lipid metabolism and aging. Their combined assessment enhances the prediction of obesity-related cardiometabolic risk, supporting their role in risk stratification and targeted interventions.

Gut microbiota has been increasingly linked to metabolic health and diseases over the past few decades. Bile acids (BAs), the major components of bile, are bidirectionally linked to intestinal microbiota, also known as the gut microbiome-BA metabolic axis. Gut microbiota-derived bile salt hydrolase (BSH, EC 3.5.1.24), which catalyzes the "gateway" reaction in a wider pathway of bile acid modification, not only shapes the bile acid landscape, but also modulates the crosstalk between gut microbiota and host health. Therefore, microbial BSHs exhibit the potential to directly or indirectly influence microbial and host physiologies, and have been increasingly considered as promising targets for the modulation of gut microbiota to benefit animal and human health. However, their physiological functions in bacterial and host physiologies are still controversial and not clear. In this review, we mainly discuss the current evidence related to the physiological roles that BSHs played in gut microbiota and human health, and the possible underlying mechanisms. Meanwhile, we also present the potential applications of BSHs and BSH-producing probiotics in various fields. Finally, we describe several important questions that need to be addressed by further investigations. A detailed exploration of the physiological significance of BSHs will contribute to their future diagnostic and therapeutic applications in improving animal and human health.

The hypothalamus-pituitary-adrenal (HPA) and gut-brain axes are vital biological pathways in depression. The HPA axis regulates the body's stress response, and chronic stress can lead to overactivation of the HPA axis, resulting in elevated cortisol levels that contribute to neuronal damage, particularly in regions such as the hippocampus and prefrontal cortex, both of which are involved in mood regulation and mental disorders. In parallel, the gut-brain axis, a bidirectional communication network between the gut microbiota and the central nervous system, influences emotional and cognitive functions. Imbalances in gut microbiota can affect the HPA axis, promoting inflammation and increasing gut permeability. This allows endotoxins to enter the bloodstream, contributing to neuroinflammation and altering neurotransmitter production, including serotonin. Since the majority of serotonin is produced in the gut, disruptions in this pathway may be linked to depressive symptoms. This review explores the interplay between the HPA axis and the gut-brain axis in the context of depression.

To evaluate the effectiveness of a cesarean delivery (CD) bundle including preoperative vaginal preparation, cefazolin and azithromycin administration, compared with cefazolin alone, in reducing postoperative infections, among women undergoing CD during the second stage of labor.

In August 2016, our departmental protocol for preventing infectious morbidity in second-stage CD was revised from preoperative intravenous 2 g cefazolin alone, to preoperative intravenous 2 g cefazolin, intravenous 500 mg azithromycin, and vaginal cleansing with povidone-iodine. In this before-and-after study, the medical records of women who underwent CD during the second stage of labor were reviewed, comparing two time periods: January 2014 to August 2016 (control group, cefazolin alone) and November 2016 to January 2021 (CD bundle group). Obstetric characteristics, postoperative infections, and neonatal outcomes were compared between groups. Composite infectious morbidity was defined as one or more of: endometritis, surgical-site infection (SSI), abscess, urinary tract infection, and postpartum fever.

During the study period, there were 5265 intrapartum CD, among them 457 were during the second stage of labor. The CD bundle group (n = 331) had lower rates of endometritis, SSI, and composite infectious morbidity compared with the control group (n = 126, 1.2% vs. 4.8%, P = 0.030; 3.0% vs. 7.1%, P = 0.049, 6.9% vs. 14.3%, P = 0.014, respectively). Neonatal outcomes did not differ between groups. Multivariable regression analysis adjusted for confounders revealed that the CD bundle reduced the risk for the composite infectious outcome, with adjusted odds ratio 0.08 (95% confidence interval 0.01-0.50).

In second-stage CD, adding preoperative azithromycin and vaginal cleansing to cefazolin was efficacious in reducing postoperative infections.

Drug-induced dysbiosis, particularly from antibiotics, has emerged as a significant contributor to chronic diseases by disrupting gut microbiota composition and function. Plant-derived secondary metabolites, such as polysaccharides, polyphenols, alkaloids, and saponins, show potential in mitigating antibiotic-induced dysbiosis. This review aims to consolidate evidence from preclinical studies on the therapeutic effects of secondary metabolites in restoring gut microbial balance, emphasizing their mechanisms and efficacy.

A narrative review was conducted using PubMed, Scopus, and Web of Science. Studies were selected based on specific inclusion criteria, focusing on animal models treated with secondary metabolites for antibiotic-induced dysbiosis. The search terms included "gut microbiota", "antibiotics", and "secondary metabolites". Data extraction focused on microbial alterations, metabolite-specific effects, and mechanisms of action. Relevant findings were systematically analyzed and summarized.

Secondary metabolites demonstrated diverse effects in mitigating the impact of dysbiosis by modulating gut microbial composition, reducing inflammation, and supporting host biological markers. Polysaccharides and polyphenols restored the Firmicutes/Bacteroidetes ratio, increased beneficial taxa such as Lactobacillus and Bifidobacterium, and suppressed pathogenic bacteria like Escherichia-Shigella. Metabolites such as triterpenoid saponins enhanced gut barrier integrity by upregulating tight junction proteins, while alkaloids reduced inflammation by modulating proinflammatory cytokines (e.g., TNF-α, IL-1β). These metabolites also improved short-chain fatty acid production, which is crucial for gut and systemic health. While antibiotic-induced dysbiosis was the primary focus, other drug classes (e.g., PPIs, metformin) require further investigation.

Plant-derived secondary metabolites show promise in managing antibiotic-induced dysbiosis by restoring microbial balance, reducing inflammation, and improving gut barrier function. Future research should explore their applicability to other types of drug-induced dysbiosis and validate findings in human studies to enhance clinical relevance.

Helicobacter pylori (H. pylori) eradication regimens may have different effects on the gut microbiota. Few studies have analyzed the safety of high-dose dual therapy (HDDT) from a micro-ecological perspective. This study aimed to compare the impact of H. pylori eradication with HDDT and bismuth quadruple therapy (BQT) on gut microbiota.

H. Pylori-infected treatment-naive patients were recruited and screened from September 2023 to April 2024 and randomly assigned to the HDDT group (esomeprazole 20 mg, amoxicillin 750 mg, qid, 14 days) or BQT group (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 600 mg, bid, 14 days). Fresh stool specimens were collected and stored before treatment and at week 2 and week 8 after treatment. The diversity and composition of the gut microbiota were compared and analyzed in both groups using 16 S rRNA gene sequencing.

Forty-nine H. pylori positive patients were enrolled and randomly assigned to either the HDDT (n = 24) or the BQT group (n = 25) group. Compared with baseline, alpha and beta diversities significantly changed at week 2 after receiving BQT and did not recover fully at week 8. However, in the HDDT group, the diversities at week 2 changed mildly without statistical significance, compared to baseline. Additionally, a greater number of species had alterations in their abundances in the BQT group compared to the HDDT group at week 2. However, the abundances of these species were restored to their previous levels at week 8 in both the HDDT and BQT groups.

Compared to BQT, HDDT exerted less impact on the diversity and composition of the gut microbiota.

ChiCTR2100053268.

The first 1, 000 days of life, from the fetal stage of a woman's pregnancy to 2 years of age after the baby is born, is a critical period for microbial colonization of the body and development of the immune system. The immune system and microbiota exhibit great plasticity at this stage and play a crucial role in subsequent development and future health. Two-way communication and interaction between immune system and microbiota is helpful to maintain human microecological balance and immune homeostasis. Currently, there is a growing interest in the important role of the microbiota in the newborn, and it is believed that the absence or dysbiosis of human commensal microbiota early in life can have lasting health consequences. Thus, this paper summarizes research advances in the establishment of the oral and intestinal microbiome and immune system in early life, emphasizing the substantial impact of microbiota diversity in the prenatal and early postnatal periods, and summarizes that maternal microbes, mode of delivery, feeding practices, antibiotics, probiotics, and the environment shape the oral and intestinal microbiota of infants in the first 1, 000 days of life and their association with the immune system.

The growing prevalence of antibiotic-resistant bacteria within the human microbiome has become a pressing global health crisis. While antibiotics have revolutionized medicine by significantly reducing mortality and enabling advanced medical interventions, their misuse and overuse have led to the emergence of resistant bacterial strains. Key resistance mechanisms include genetic mutations, horizontal gene transfer, and biofilm formation, with the human microbiota acting as a reservoir for antibiotic resistance genes (ARGs). Industrialization and environmental factors have exacerbated this issue, contributing to a rise in infections with multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae. These resistant pathogens compromise the effectiveness of essential treatments like surgical prophylaxis and chemotherapy, increase healthcare costs, and prolong hospital stays. This crisis highlights the need for a global One-Health approach, particularly in regions with weak regulatory frameworks. Innovative strategies, including next-generation sequencing (NGS) technologies, offer promising avenues for mitigating resistance. Addressing this challenge requires coordinated efforts, encompassing research, policymaking, public education, and antibiotic stewardship, to safeguard current antibiotics and foster the development of new therapeutic solutions. An integrated, multidimensional strategy is essential to tackle this escalating problem and ensure the sustainability of effective antimicrobial treatments.

Chicken bile is a by-product of chicken processing, rich in chenodeoxycholic acid (CDCA), an active pharmaceutical raw material. In this study, a green measure for the extraction and purification of CDCA from chicken biles by enzymatic hydrolysis and macroporous resins refining was established. For the assisted extraction of CDCA, the active bile salt hydrolase (BSH) from Bifidobacterium was heterologously expressed and applied, its activities on GCDCA and TCDCA were 4.96 ± 0.32 U/mg and 3.07 ± 0.031 U/mg and optimal catalytic conditions for the extraction of CDCA were determined as 0.04 g/g of the enzyme dosage, pH 5.0 and 38 °C. Through validation of the conditions, the yield of CDCA was up to 5.32 %, which was equivalent to that by saponification method. In order to further refine CDCA from the extract obtained by enzyme-assisted extraction, a more preferable resin, AB-8 was selected for the purification of CDCA, which had a good adsorption capacity of 61.06 ± 0.57 mg/g for CDCA. Besides, the obtained CDCA extract was purified through AB-8 resin, the purity of CDCA was improved from 51.7 % to 91.4 % and the recovery yield of CDCA was 87.8 %. The advantages of energy conservation, time saving, economy and environmental friendliness make the measure using enzyme-assisted extraction and macroporous resins refining a promising candidate for isolation of CDCA from chicken bile.

Gut microbiota is important for host metabolism regulation. Antibiotic exposure disturbs this regulation by affecting the microbiome. Trace levels of antibiotics in water have been widely reported and the impact on gut microbiota remains understudied. We provide evidence of trace antibiotic exposure affecting the host's gut microbiota using a mouse model exposed to trace amounts of azithromycin (AZI) or ciprofloxacin (CIP) in drinking water. AZI exposure in males changed the distribution of gram-positive (Firmicutes and Bacteroidetes) and gram-negative (Proteobacteria, Fusobacteria, and Verrucomicrobia) bacteria at an early age. Both AZI and CIP resulted in abnormal microbiota maturation. Additionally, the production of short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, in females is affected. Serum hormone and metabolome levels shifted after trace antibiotic exposure. AZI and CIP exposure broadly disrupted original host-microbe interaction relationships between the gut microbiota and SCFAs or serum metabolites. In this study, we demonstrated that trace antibiotic exposure was associated with extensive gut microbiota and metabolism perturbation in mice and that the potential health risks in susceptible populations should be considered.

Many studies have demonstrated the impact of intestinal microbiota on normal brain development. Moreover, the gut microbiota (GM) is impacted by multiple endogenous and environmental factors that may promote gut dysbiosis (GD). An increasing number of studies are investigating the possible role of the GD in the development of neurological and behavioral disorders. For autism spectrum disorders (ASD), specific intestinal bacterial signatures have been identified, knowing that gastrointestinal symptoms are frequently found in ASD. In this review, the peri and post-natal factors modulating the GM are described and the specific gut bacterial signature of ASD children is detailed. Through bidirectional communication between the GM and the brain, several mechanisms are involved in the development of ASD, such as cytokine-mediated neuroinflammation and decreased production of neuroprotective factors such as short-chain fatty acids by the GM. Imbalance of certain neurotransmitters such as serotonin or gamma-aminobutyric acid could also play a role in these gut-brain interactions. Some studies show that this GD in ASD is partly reversible by treatment with pre- and probiotics, or fecal microbiota transplantation with promising results. However, certain limitations have been raised, in particular concerning the short duration of treatment, the small sample sizes and the diversity of protocols. The development of standardized therapeutics acting on GD in large cohort could rescue the gastrointestinal symptoms and behavioral impairments, as well as patient management.

Socioeconomic (SE) disparity and health inequity are closely intertwined and associated with cross-generational increases in the rates of multiple chronic non-communicable diseases (NCDs) in North America and beyond. Coinciding with this social trend is an observed loss of biodiversity within the community of colonizing microbes that live in and on our bodies. Researchers have rightfully pointed to the microbiota as a key modifiable factor with the potential to ease existing health inequities. Although a number of studies have connected the adult microbiome to socioeconomic determinants and health outcomes, few studies have investigated the role of the infant microbiome in perpetuating these outcomes across generations. It is an essential and important question as the infant microbiota is highly sensitive to external forces, and observed shifts during this critical window often portend long-term outcomes of health and disease. While this is often studied in the context of direct modulators, such as delivery mode, family size, antibiotic exposure, and breastfeeding, many of these factors are tied to underlying socioeconomic and/or cross-generational factors. Exploring cross-generational socioeconomic and health inequities through the lens of the infant microbiome may provide valuable avenues to break these intergenerational cycles. In this review, we will focus on the impact of social inequality in infant microbiome development and discuss the benefits of prioritizing and restoring early-life microbiota maturation for reducing intergenerational health disparities.

Children are the age group with the highest exposure to antibiotics (ABX). ABX treatment changes the composition of the intestinal microbiota. The first few years of life are crucial for the establishment of a healthy microbiota and consequently, disturbance of the microbiota during this critical period may have far-reaching consequences. In this review, we summarise studies that have investigated the effect of ABX on the composition of the intestinal microbiota in children.

According to the PRISMA guidelines, a systematic search was done using MEDLINE and Embase to identify original studies that have investigated the effect of systemic ABX on the composition of the intestinal microbiota in children.

We identified 89 studies investigating a total of 9,712 children (including 4,574 controls) and 14,845 samples. All ABX investigated resulted in a reduction in alpha diversity, either when comparing samples before and after ABX or children with ABX and controls. Following treatment with penicillins, the decrease in alpha diversity persisted for up to 6-12 months and with macrolides, up to the latest follow-up at 12-24 months. After ABX in the neonatal period, a decrease in alpha diversity was still found at 36 months. Treatment with penicillins, penicillins plus gentamicin, cephalosporins, carbapenems, macrolides, and aminoglycosides, but not trimethoprim/sulfamethoxazole, was associated with decreased abundances of beneficial bacteria including Actinobacteria, Bifidobacteriales, Bifidobacteriaceae, and/or Bifidobacterium, and Lactobacillus. The direction of change in the abundance of Enterobacteriaceae varied with ABX classes, but an increase in Enterobacteriaceae other than Escherichia coli was frequently observed.

ABX have profound effects on the intestinal microbiota of children, with notable differences between ABX classes. Macrolides have the most substantial impact while trimethoprim/sulfamethoxazole has the least pronounced effect.

Childhood asthma is among the most common chronic lung diseases in the pediatric population, having substantial consequences on the everyday life of children and their caregivers. There remains a lack of a singular, efficacious strategy for averting the inception of childhood asthma. The rate of pediatric antibiotic usage continues to be high, which makes it crucial to understand whether there exists a causal link between the use of antibiotics in infancy and the development of asthma in childhood. In this rostrum, we conduct a critical review of the literature concerning the association of infant antibiotic use and the onset of childhood asthma. Drawing on the results of 5 meta-analyses addressing this topic and of a recent randomized controlled trial, a notable association emerges between antibiotic exposure in the first year of life and the occurrence of childhood asthma that appears to be beyond potential study limitations (such as reverse causation, confounding by indication, and recall bias). Furthermore, we highlight the need for additional research in this field that could improve our understanding of important aspects of this association and lead to the design of an intervention aimed to deliver antibiotics safely during early life and reduce the burden of childhood asthma.

The human gut microbiota is central in regulating all facets of host physiology, and in early life it is thought to influence the host's immune system and metabolism, affecting long-term health. However, longitudinally monitored cohorts with parallel analysis of faecal samples and health data are scarce. In our observational study we describe the gut microbiota development in the first 2 years of life and create a gut microbiota wellbeing index based on the microbiota development and health data in a cohort of nearly 1000 infants using clustering and trajectory modelling. We show that infants' gut microbiota development is highly predictable, following one of five trajectories, dependent on infant exposures, and predictive of later health outcomes. We characterise the natural healthy gut microbiota trajectory and several different dysbiotic trajectories associated with different health outcomes. Bifidobacterium and Bacteroides appear as early keystone organisms, directing microbiota development and consistently predicting positive health outcomes. A microbiota wellbeing index, based on the healthy development trajectory, is predictive of general health over the first 5 years. The results indicate that gut microbiota succession is part of infant physiological development, predictable, and malleable. This information can be utilised to improve the predictions of individual health risks.

Since the advent of new sequencing and bioinformatic technologies, our understanding of the human microbiome has expanded rapidly over recent years. Numerous studies have indicated causal links between alterations to the microbiome and a range of pathological conditions. Furthermore, a large body of epidemiological data is starting to suggest that exposure, or lack thereof, to specific microbial species during the first five years of life has key implications for long-term health outcomes. These include chronic inflammatory and metabolic conditions such as diabetes, asthma, inflammatory bowel disease (IBD), and obesity, with the effects lasting into adulthood. Human microbial colonisation during these first five years of life is a highly dynamic process, with multiple environmental exposures recently being characterised to have influence before the microbiome stabilises and resembles that of an adult at 3-5 years. This short period of time, known as the window of opportunity, appears to "prime" immunoregulation for later life. Understanding and appreciating this aspect of human physiology is therefore crucial for clinicians, scientists, and public health officials. This review outlines the most recent evidence for the pre- and post-natal environments that order the development of the microbiome, how these influences metabolic and immunoregulatory pathways, and their associated health outcomes. It also discusses the limitations of the current knowledge base, and describes the potential microbiome-mediated interventions and public health measures that may have therapeutic potential in the future.

The emerging field of gut-lung axis research has revealed a complex interplay between the gut microbiota and respiratory health, particularly in asthma. This review comprehensively explored the intricate relationship between these two systems, focusing on their influence on immune responses, inflammation, and the pathogenesis of respiratory diseases. Recent studies have demonstrated that gut microbiota dysbiosis can contribute to asthma onset and exacerbation, prompting investigations into therapeutic strategies to correct this imbalance. Probiotics and prebiotics, known for their ability to modulate gut microbial compositions, were discussed as potential interventions to restore immune homeostasis. The impact of antibiotics and metabolites, including short-chain fatty acids produced by the gut microbiota, on immune regulation was examined. Fecal microbiota transplantation has shown promise in various diseases, but its role in respiratory disorders is not established. Innovative approaches, including mucus transplants, inhaled probiotics, and microencapsulation strategies, have been proposed as novel therapeutic avenues. Despite challenges, including the sophisticated adaptability of microbial communities and the need for mechanistic clarity, the potential for microbiota-based interventions is considerable. Collaboration between researchers, clinicians, and other experts is essential to unravel the complexities of the gut-lung axis, paving a way for innovative strategies that could transform the management of respiratory diseases.

Pregnant women undergoing a cesarean section (CS) typically receive antibiotics prior to skin incision to prevent infections. To investigate if the timing of antibiotics influences the infant gut microbiome, we conducted a randomized controlled trial (NCT06030713) in women delivering via a scheduled CS who received antibiotics either before skin incision or after umbilical cord clamping. We performed a longitudinal analysis on 172 samples from 28 infants at 8 post-birth time points and a cross-sectional analysis at 1 month in 79 infants from 3 cohorts. Although no significant associations with bacterial composition, metabolic pathways, short-chain fatty acids, and bile acids were found, we observed subtle differences between the groups at the bacterial strain level and in the load of antibiotic resistance genes. Rather, feeding mode was a predominant and defining factor impacting infant microbial composition. In conclusion, antibiotic administration during CS has only limited effects on the early-life gut microbiome.

To investigate the rate of dispensed antibiotic prescriptions to children and adolescents with PFAPA and compare this with the rate for children in the general population. Furthermore, to compare dispensed antibiotic prescription rates before and after a diagnosis of PFAPA was established.

Patients aged 0-17 years and diagnosed with PFAPA between 1 January 2006 to 31 October 2017 were included retrospectively. Data on dispensed drug prescriptions were obtained from the Swedish National Prescribed Drug Register.

The PFAPA cohort received more antibiotic prescriptions than the general population in all but one of the age groups and time periods that were analysed. The largest difference was seen in 2014-2017 in the youngest age group (0-4 years) when children with PFAPA received 1218 antibiotic prescriptions per 1000 person years compared to 345 in the general population (IRR 3.5; 95% CI 2.8-4.4). The yearly number of antibiotic prescriptions to PFAPA patients was reduced from 2.1 before diagnosis to 0.8 after diagnosis, a reduction of 62%.

This study shows higher rates of dispensed antibiotic prescriptions for children with PFAPA than in the general population. The reduction of prescriptions after an established PFAPA diagnosis indicates that antibiotics were previously incorrectly prescribed for PFAPA episodes.

Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea (AAD) in hospitals in the developed world. Both infected patients and asymptomatic colonized individuals represent important transmission sources of C. difficile. C. difficile infection (CDI) shows a large range of symptoms, from mild diarrhea to severe manifestations such as pseudomembranous colitis. Epidemiological changes in CDIs have been observed in the last two decades, with the emergence of highly virulent types and more numerous and severe CDI cases in the community. C. difficile interacts with the gut microbiota throughout its entire life cycle, and the C. difficile's role as colonizer or invader largely depends on alterations in the gut microbiota, which C. difficile itself can promote and maintain. The restoration of the gut microbiota to a healthy state is considered potentially effective for the prevention and treatment of CDI. Besides a fecal microbiota transplantation (FMT), many other approaches to re-establishing intestinal eubiosis are currently under investigation. This review aims to explore current data on C. difficile and gut microbiota changes in colonized individuals and infected patients with a consideration of the recent emergence of highly virulent C. difficile types, with an overview of the microbial interventions used to restore the human gut microbiota.

The microbiome is known to have a substantial impact on human health and disease. However, the impacts of the microbiome on immune system development, susceptibility to infectious diseases, and vaccine-elicited immune responses are emerging areas of interest.

In this review, we provide an overview of development of the microbiome during childhood. We highlight available data suggesting that the microbiome is critical to maturation of the immune system and modifies susceptibility to a variety of infections during childhood and adolescence, including respiratory tract infections, Clostridioides difficile infection, and sexually transmitted infections. We discuss currently available and investigational therapeutics that have the potential to modify the microbiome to prevent or treat infections among children. Finally, we review the accumulating evidence that the gut microbiome influences vaccine-elicited immune responses among children.

Recent advances in sequencing technologies have led to an explosion of studies associating the human microbiome with the risk and severity of infectious diseases. As our knowledge of the extent to which the microbiome influences childhood infections continues to grow, microbiome-based diagnostics and therapeutics will increasingly be incorporated into clinical practice to improve the prevention, diagnosis, and treatment of infectious diseases among children.

Microbial imbalance in the gut from antibiotic use may be an etiologic factor of Kawasaki disease (KD). We aimed to identify the association between the use of antibiotics and the development of KD, considering various antibiotic profiles.

A population-based, case-control study was performed using data from the Health Insurance Review and Assessment Service database. Children <5 years of age, who were diagnosed with KD between 2016 and 2019, were identified. Propensity score-matched controls were selected from the general population in a 1:5 ratio. Four separate study cohorts were created according to different periods of antibiotic use: (1) within 28 days and (2) 12 months after birth and (3) within 6 months and (4) 12 months from the index date. Profiles regarding antibiotic use were compared between patients with KD and matched controls.

We included 17,818 patients with KD and 89,090 matched controls. Use of antibiotics within 6 months [odds ratio (OR): 1.18; 95% confidence interval (CI): 1.12-1.26] and 12 months (OR: 1.23; 95% CI: 1.14-1.32) from the index date were associated with the development of KD. The association between antibiotic use and KD was most prominent in patients who had received 3 or more types of antibiotics within 12 months from the index date (OR: 1.26; 95% CI: 1.17-1.37).

Antibiotic use within the preceding 6 or 12 months was associated with KD. Alteration in gut microbiota due to antibiotic usage might play a role in the development of KD.

Several hypotheses link reduced microbial exposure to increased prevalence of allergies. Here we capitalize on the opportunity to study a cohort of infants (CORAL), raised during COVID-19 associated social distancing measures, to identify the environmental exposures and dietary factors that contribute to early life microbiota development and to examine their associations with allergic outcomes.

Fecal samples were sequenced from infants at 6 (n = 351) and repeated at 12 (n = 343) months, using 16S sequencing. Published 16S data from pre-pandemic cohorts were included for microbiota comparisons. Online questionnaires collected epidemiological information on home environment, healthcare utilization, infant health, allergic diseases, and diet. Skin prick testing (SPT) was performed at 12 (n = 343) and 24 (n = 320) months of age, accompanied by atopic dermatitis and food allergy assessments.

The relative abundance of bifidobacteria was higher, while environmentally transmitted bacteria such as Clostridia was lower in CORAL infants compared to previous cohorts. The abundance of multiple Clostridia taxa correlated with a microbial exposure index. Plant based foods during weaning positively impacted microbiota development. Bifidobacteria levels at 6 months of age, and relative abundance of butyrate producers at 12 months of age, were negatively associated with AD and SPT positivity. The prevalence of allergen sensitization, food allergy, and AD did not increase over pre-pandemic levels.

Environmental exposures and dietary components significantly impact microbiota community assembly. Our results also suggest that vertically transmitted bacteria and appropriate dietary supports may be more important than exposure to environmental microbes alone for protection against allergic diseases in infancy.

Gut dysbiosis has been associated with impaired outcomes in liver and kidney transplant recipients, but the gut microbiome of lung transplant recipients has not been extensively explored. We assessed the gut microbiome in 64 fecal samples from end-stage lung disease patients before transplantation and 219 samples from lung transplant recipients after transplantation using metagenomic sequencing. To identify dysbiotic microbial signatures, we analyzed 243 fecal samples from age-, sex-, and BMI-matched healthy controls. By unsupervised clustering, we identified five groups of lung transplant recipients using different combinations of immunosuppressants and antibiotics and analyzed them in relation to the gut microbiome. Finally, we investigated the gut microbiome of lung transplant recipients in different chronic lung allograft dysfunction (CLAD) stages and longitudinal gut microbiome changes after transplantation. We found 108 species (58.1%) in end-stage lung disease patients and 139 species (74.7%) in lung transplant recipients that were differentially abundant compared with healthy controls, with several species exhibiting sharp longitudinal increases from before to after transplantation. Different combinations of immunosuppressants and antibiotics were associated with specific gut microbial signatures. We found that the gut microbiome of lung transplant recipients in CLAD stage 0 was more similar to healthy controls compared to those in CLAD stage 1. Finally, the gut microbial diversity of lung transplant recipients remained lower than the average gut microbial diversity of healthy controls up to more than 20 years post-transplantation. Gut dysbiosis, already present before lung transplantation was exacerbated following lung transplantation.IMPORTANCEThis study provides extensive insights into the gut microbiome of end-stage lung disease patients and lung transplant recipients, which warrants further investigation before the gut microbiome can be used for microbiome-targeted interventions that could improve the outcome of lung transplantation.

Recent studies have highlighted the impact of disrupted maternal gut microbiota on the colonization of offspring gut microbiota, with implications for offspring developmental trajectories. The extent to which offspring inherit the characteristics of altered maternal gut microbiota remains elusive. In this study, we employed a mouse model where maternal gut microbiota disruption was induced using non-absorbable antibiotics. Systematic chronological analyses of dam fecal samples, offspring luminal content, and offspring gut tissue samples revealed a notable congruence between offspring gut microbiota profiles and those of the perturbed maternal gut microbiota, highlighting the profound influence of maternal microbiota on early-life colonization of offspring gut microbiota. Nonetheless, certain dominant bacterial genera in maternal microbiota did not transfer to the offspring, indicating a bacterial taxonomy-dependent mechanism in the inheritance of maternal gut microbiota. Our results embody the vertical transmission dynamics of disrupted maternal gut microbiota in an animal model, where the gut microbiota of an offspring closely mirrors the gut microbiota of its mother.

The evolution of the gut-microbiota-brain axis in animals reveals that microbial inputs influence metabolism, the regulation of inflammation and the development of organs, including the brain. Inflammatory, neurodegenerative and psychiatric disorders are more prevalent in people of low socioeconomic status (SES). Many aspects of low SES reduce exposure to the microbial inputs on which we are in a state of evolved dependence, whereas the lifestyle of wealthy citizens maintains these exposures. This partially explains the health deficit of low SES, so focussing on our evolutionary history and on environmental and lifestyle factors that distort microbial exposures might help to mitigate that deficit. But the human microbiota is complex and we have poor understanding of its functions at the microbial and mechanistic levels, and in the brain. Perhaps its composition is more flexible than the microbiota of animals that have restricted habitats and less diverse diets? These uncertainties are discussed in relation to the encouraging but frustrating results of attempts to treat psychiatric disorders by modulating the microbiota.

Broad-spectrum antibiotics are frequently used to treat bacteria-induced infections, but the overuse of antibiotics may induce the gut microbiota dysbiosis and disrupt gastrointestinal tract function. Probiotics can be applied to restore disturbed gut microbiota and repair abnormal intestinal metabolism. In the present study, two strains of Enterococcus faecium (named DC-K7 and DC-K9) were isolated and characterized from the fecal samples of infant dogs. The genomic features of E. faecium DC-K7 and DC-K9 were analyzed, the carbohydrate-active enzyme (CAZyme)-encoding genes were predicted, and their abilities to produce short-chain fatty acids (SCFAs) were investigated. The bacteriocin-encoding genes in the genome sequences of E. faecium DC-K7 and DC-K9 were analyzed, and the gene cluster of Enterolysin-A, which encoded a 401-amino-acid peptide, was predicted. Moreover, the modulating effects of E. faecium DC-K7 and DC-K9 on the gut microbiota dysbiosis induced by antibiotics were analyzed. The current results demonstrated that oral administrations of E. faecium DC-K7 and DC-K9 could enhance the relative abundances of beneficial microbes and decrease the relative abundances of harmful microbes. Therefore, the isolated E. faecium DC-K7 and DC-K9 were proven to be able to alter the gut microbiota dysbiosis induced by antibiotic treatment.

The field of bile acid microbiology in the gastrointestinal tract is going through a current rebirth after a peak of activity in the late 1970s and early 1980s. This renewed activity is a result of many factors, including the discovery near the turn of the century that bile acids are potent signalling molecules and technological advances in next-generation sequencing, computation, culturomics, gnotobiology, and metabolomics. We describe the current state of the field with particular emphasis on questions that have remained unanswered for many decades in both bile acid synthesis by the host and metabolism by the gut microbiota. Current knowledge of established enzymatic pathways, including bile salt hydrolase, hydroxysteroid dehydrogenases involved in the oxidation and epimerization of bile acid hydroxy groups, the Hylemon-Bjӧrkhem pathway of bile acid C7-dehydroxylation, and the formation of secondary allo-bile acids, is described. We cover aspects of bile acid conjugation and esterification as well as evidence for bile acid C3-dehydroxylation and C12-dehydroxylation that are less well understood but potentially critical for our understanding of bile acid metabolism in the human gut. The physiological consequences of bile acid metabolism for human health, important caveats and cautionary notes on experimental design and interpretation of data reflecting bile acid metabolism are also explored.

Early life antibiotic exposure may increase obesity risk. We investigated if prenatal, intrapartum, or childhood antibiotic use is associated with child zBMI score at 4 yrs of age. We included data from the Alberta Pregnancy Outcomes and Nutrition (APrON) study, a prospective cohort study, on maternal and child antibiotic exposure and clinic measures of height and weight at age 4 (n = 408). Prenatal and childhood antibiotic exposure was not associated with zBMI score. Maternal intrapartum antibiotic exposure was associated with a zBMI score increase of 0.12 (95 % CI; 0.04, 0.46) in children at 4 years of age compared to non-exposure intrapartum.

This study investigated the effects of an antibiotic cocktail on intestinal microbial composition, mechanical barrier structure, and immune functions in early broilers. One-day-old healthy male broiler chicks were treated with a broad-spectrum antibiotic cocktail (ABX; neomycin, ampicillin, metronidazole, vancomycin, and kanamycin, 0.5 g/L each) or not in drinking water for 7 and 14 days, respectively. Sequencing of 16S rRNA revealed that ABX treatment significantly reduced relative Firmicutes, unclassified Lachnospiraceae, unclassified Oscillospiraceae, Ruminococcus torques, and unclassified Ruminococcaceae abundance in the cecum and relative Firmicutes, Lactobacillus and Baccillus abundance in the ileum, but significantly increased richness (Chao and ACE indices) and relative Enterococcus abundance in the ileum and cecum along with relatively enriched Bacteroidetes, Proteobacteria, Cyanobacteria, and Enterococcus levels in the ileum following ABX treatment for 14 days. ABX treatment for 14 days also significantly decreased intestinal weight and length, along with villus height (VH) and crypt depth (CD) of the small intestine, and remarkably increased serum LPS, TNF-α, IFN-γ, and IgG levels, as well as intestinal mucosa DAO and MPO activity. Moreover, prolonged use of ABX significantly downregulated occludin, ZO-1, and mucin 2 gene expression, along with goblet cell numbers in the ileum. Additionally, chickens given ABX for 14 days had lower acetic acid, butyric acid, and isobutyric acid content in the cecum than the chickens treated with ABX for 7 days and untreated chickens. Spearman correlation analysis found that those decreased potential beneficial bacteria were positively correlated with gut health-related indices, while those increased potential pathogenic strains were positively correlated with gut inflammation and gut injury-related parameters. Taken together, prolonged ABX application increased antibiotic-resistant species abundance, induced gut microbiota dysbiosis, delayed intestinal morphological development, disrupted intestinal barrier function, and perturbed immune response in early chickens. This study provides a reliable lower-bacteria chicken model for further investigation of the function of certain beneficial bacteria in the gut by fecal microbiota transplantation into germ-free or antibiotic-treated chickens.

The gut microbiota is hypothesized as a prognostic biomarker for cancer immunotherapy. Antibiotic-induced dysbiosis negatively affects the clinical outcomes of immunotherapy. However, the effect of dysbiosis on the efficacy and safety of Chemoimmunotherapy (chemo-IOs), the frontline standard of care, in advanced non-small cell lung cancer (NSCLC) remains unknown. We aimed to compare the efficacy and safety of chemo-IOs in patients exposed to antibiotics before treatment with those of patients who were not exposed.

We retrospectively reviewed patients with advanced NSCLC treated with first-line chemo-IOs between 2018 and 2020 at the National Cancer Center Hospital. The patients were divided into two groups: those exposed to antibiotics within 30 days before induction therapy (ABx group) and those did not antibiotics (Non-ABx group). Propensity score matching was used to control for potential confounding factors. Clinical outcomes including progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were compared.

Of 201 eligible patients, 21 were in the ABx group, and 42 were in the non-ABx group after propensity score matching. No differences in PFS or OS emerged between the two groups (ABx group vs. Non-ABx group) (PFS:7.0 months vs. 6.4 months, hazard ratio [HR] 0.89; 95% confidence interval [CI], 0.49-1.63, OS:20.4 months vs. 20.1 months, HR 0.87; 95% CI 0.44-1.71). The frequency of irAEs before propensity score matching was similar across any-grade irAEs (39.4% vs. 42.9%) or grade 3 or higher irAEs (9.1% vs. 11.3%).

Antibiotic-induced dysbiosis may not affect the efficacy of chemo-IOs in patients with advanced NSCLC.