The development of the gut microbiome is crucial to human health, particularly during the first three years of life. Given its role in immune development, disturbances in the establishment process of the gut microbiome may have long term consequences. This review summarizes evidence for these claims, highlighting compositional changes of the gut microbiome during this critical period of life as well as factors that affect gut microbiome development. Based on human and animal data, we conclude that the early-life microbiome is a determinant of long-term health, impacting physiological, metabolic, and immune processes. The early-life gut microbiome field faces challenges. Some of these challenges are technical, such as lack of standardized stool collection protocols, inconsistent DNA extraction methods, and outdated sequencing technologies. Other challenges are methodological: small sample sizes, lack of longitudinal studies, and poor control of confounding variables. To address these limitations, we advocate for more robust research methodologies to better understand the microbiome's role in health and disease. Improved methods will lead to more reliable microbiome studies and a deeper understanding of its impact on health outcomes.

Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.

Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD) is increasing in prevalence worldwide and has become the greatest potential risk for cirrhosis and hepatocellular liver cancer. Currently, the role of gut microbiota in the development of MASLD has become a research hotspot. The development of MASLD can affect the homeostasis of gut microbiota, and significant changes in the composition or abundance of gut microbiota and its metabolite abnormalities can influence disease progression. The regulation of gut microbiota is an important strategy and novel target for the treatment of MASLD with good prospects. In this paper, we summarize the role of gut microbiota and its metabolites in the pathogenesis of MASLD, and describe the potential preventive and therapeutic efficacy of gut microbiota as a noninvasive marker to regulate the pathogenesis of MASLD based on the "gut-hepatic axis", which will provide new therapeutic ideas for the clinic.

Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome. Recent clinical trials have indicated that gut microbiome modulation using probiotics, prebiotics, and fecal microbiota transplantation (FMT) led to improvements in multiple symptoms related to PACS, including fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and disturbances in sleep and mood. In this review, we highlight the latest evidence on the key microbial alterations observed in PACS, as well as the use of microbiome-based therapeutics in managing PACS symptoms. These novel findings altogether shed light on the treatment of PACS and other chronic conditions.

Partial RAG deficiency (pRD) can manifest with systemic and tissue-specific immune dysregulation, with inflammatory bowel disease (IBD) in 15% of the patients. We aimed at identifying the immunopathological and microbial signatures associated with IBD in patients with pRD and in a mouse model of pRD (Rag1w/w) with spontaneous development of colitis. pRD patients with IBD and Rag1w/w mice showed a systemic and colonic Th1/Th17 inflammatory signature. Restriction of fecal microbial diversity, abundance of pathogenic bacteria, and depletion of microbial species producing short-chain fatty acid were observed, which were associated with impaired induction of lamina propria peripheral Treg cells in Rag1w/w mice. The use of vedolizumab in Rag1w/w mice and of ustekinumab in a pRD patient were ineffective. Antibiotics ameliorated gut inflammation in Rag1w/w mice, but only bone marrow transplantation (BMT) rescued the immunopathological and microbial signatures. Our findings shed new light in the pathophysiology of gut inflammation in pRD and establish a curative role for BMT to resolve the disease phenotype.

The impact of behaviors on the microbiome, and in turn its effects on health, are increasingly recognized by the scientific and medical communities. Yet little is known about public understandings of the microbiome and the relationships with health. We developed a semi-structured interview tool covering topics from microbiome composition to behavioral factors affecting microbiomes and related health throughout the life course. Drawing on semi-structured interviews conducted in 2021-22 with 32 US women purposefully recruited from 5 demographic categories (with pets, chronic illness, young children, complementary and alternative medicine use, and elders), we explore perspectives on topics including microbiome and diet, medicine use, cleaning practices, and travel. We conducted a thematic analysis, tallied response frequencies of elicited themes, and plotted emerging themes on semantic maps to provide visual representations of connections between concepts, and commonly mentioned metaphors to identify promising new lines of inquiry on public understandings of the microbiome. We observed interconnections between domains, as shown in semantic maps, and examples of ecological and militaristic analogies. Participants used analogies to estimate duration of microbiome disruption and recovery. Metaphors provide scaffolding for organizing new information about the microbiome and influence how people make choices about when and how to kill or promote microbes in their bodies and their environment. Characterizing these public understandings of microbiomes and linkages to health behaviors among different demographic groups is critical to designing and implementing health education and policy and informing future research inquiries in a participatory way through public-research collaborations.

Numerous studies have shown an interconnection between the gut microbiota and the brain via the "gut-brain" axis. However, the causal relationships between gut microbiota, lipids, and neuropsychiatric disorders remain unclear. This study aimed to analyze potential associations among gut microbiota, lipids, and neuropsychiatric disorders-including AD, PD, ALS, MS, SCZ, MDD, and BD-using summary data from large-scale GWAS.

Bidirectional Mendelian randomization (MR) with inverse variance weighting (IVW) was the primary method. Supplementary analyses included sensitivity analyses, Steiger tests, and Bayesian weighted MR (BWMR). Mediation analyses used two-step MR (TSMR) and multivariable MR (MVMR).

The analyses revealed 51 positive correlations (risk factors) (β > 0, P < 0.05) and 47 negative correlations (protective factors) (β < 0, P < 0.05) between gut microbiota and neuropsychiatric disorders. In addition, 35 positive correlations (β > 0, P < 0.05) and 22 negative correlations (β < 0, P < 0.05) between lipids and neuropsychiatric disorders were observed. Assessment of reverse causality with the seven neuropsychiatric disorders as exposures and the identified gut microbiota and lipids as outcomes revealed no evidence of reverse causality (P > 0.05). Mediation analysis indicated that the effect of the species Bacteroides plebeius on MDD is partially mediated through the regulation of phosphatidylcholine (16:0_20:4) levels (mediation proportion = 10.9 % [95 % CI = 0.0110-0.2073]).

This study provides evidence of a causal relationship between gut microbiota and neuropsychiatric disorders, suggesting lipids as mediators. These findings offer new insights into the mechanisms by which gut microbiota may influence neuropsychiatric disorders.

Co-pollution of microplastics (MPs) and novel brominated flame retardants (NBFRs) in aquatic environments is becoming increasingly common in aquatic environments, raising concerns about their comprehensive ecological impacts. This study investigated the effects of fibrous polyethylene terephthalate (PET) MPs on the bioaccumulation and toxicity of decabromodiphenyl ethane (DBDPE) in zebrafish (Danio rerio). In a 28-day water exposure experiment, co-exposure of fibrous MPs and DBDPE significantly increased the bioavailability of DBDPE in zebrafish and prolonged the half-life of DBDPE in vivo. The elimination rates of DBDPE concentration in muscles of single DBDPE exposure and co-exposure groups were 61.58 % and 56.63 %, respectively. Additionally, the co-exposure exacerbated intestinal damage, including structural deterioration and nutrients depletion, disrupted gut microbiota, promoted the enrichment of genes related to reproductive toxicity, and affected the gut-brain axis, indicating complex toxic interactions in zebrafish. Furthermore, genera of Aurantimicrobium, Cypionkella, and Gemmobacter were the gut microbes significantly associated with main differentially expressed genes(DEGs)in the brain. This study emphasized the exacerbating role of fibrous MPs in DBDPE toxicity, providing new insights into the ecological risks posed by the coexistence of MPs and NBFRs in aquatic ecosystems.

Over the past 3 years, there has been a growing interest in clinical research regarding the potential involvement of intestinal flora in thyroid cancer (TC). This review delves into the intricate connection between intestinal flora and TC, focusing on the particular intestinal flora that is directly linked to the disease and identifying which may be able to predict potential microbial markers of TC. In order to shed light on the inflammatory pathways connected to the onset of TC, we investigated the impact of intestinal flora on immune modulation and the connection between chronic inflammation when investigating the role of intestinal flora in the pathogenesis of TC. Furthermore, the potential role of intestinal flora metabolites in the regulation of thyroid function was clarified by exploring the effects of short-chain fatty acids and lipopolysaccharide on thyroid hormone synthesis and metabolism. Based on these findings, we further explore the effects of probiotics, prebiotics, postbiotics, vitamins, and trace elements.

When the available human-derived information at a crime scene is limited, it poses challenges in determining the origin of the biological materials and identifying their donors. In this context, microorganisms have gradually emerged as a valuable complementary tool. Nowadays, the application of third-generation sequencing technology for full-length 16S rRNA sequencing to explore the specific bacterial biomarkers in various biological materials holds significant research and practical value. In this study, we performed full-length 16S rRNA gene sequencing on sterile swabs from palmar skin, oral mucosa, and nasal cavity using the PacBio single-molecule real-time sequencing (SMRT) platform. Alongside identifying specific bacterial biomarkers for these biological materials from different body sites, the study also preliminarily explored the specific bacterial taxa in 19 individuals at the phylum, genus, and species levels. The results showed that the palmar skin bacteria primarily consist of Cutibacterium, Staphylococcus, and Streptococcus, the oral mucosal bacteria are dominated by Streptococcus, Neisseria, and Haemophilus, while the dominant bacteria in nasal cavity are Staphylococcus and Cutibacterium. Beta diversity analysis revealed significant differences in the bacterial community composition across the three origins of biological materials. Furthermore, classification models based on the bacterial species were constructed using the Random Forest, XGBoost, and KNN algorithms. The results showed that both Random Forest and XGBoost models achieved an accuracy of 97 %, significantly outperforming the KNN model (79 %). The prediction accuracy at the OTU level was comparable to that at the species level. In addition, bacterial community differences between individuals were observed at both the genus and species levels. Overall, this study further explores the potential of classification prediction methods based on bacterial features for distinguishing the body site origins of different biological materials and enabling individual traceability, thereby providing valuable data to support the application of microbiological techniques in forensic practice.

Probiotic bacteria play a vital role in maintaining gut microbial homeostasis and are widely used in various commercial products. Although 16S rRNA amplicon-based next-generation sequencing (NGS) is commonly used to analyze probiotic products, biases can arise from various 16S rRNA amplification regions, sequencing platforms, and library kits. In this study, a reference-based bias correction model was developed to correct sequencing biases. The model was validated using eight mock communities and 12 commercial products, which were analyzed across multiple NGS platforms and various 16S rRNA regions. Specific primer-probe assays were developed for accurate bacterial quantification, and their specificity was validated and used in conjunction with droplet digital PCR (ddPCR) to establish initial bacterial ratios within communities. Analysis of the mock communities revealed platform- and region-specific biases, with specific species consistently over- or under-represented. Similarly, commercial product analyses have shown biased outcomes owing to varying sequencing protocols. The correction model, based on PCR efficiencies from the reference communities, successfully corrected biased ratios across different amplification regions and platforms to achieve results that closely matched the proportions predicted by ddPCR. The model effectively corrected the biases arising from the different polymerases. Notably, partial references containing approximately 40 % of the species achieved correction results that were comparable to those of the complete references. This approach demonstrates the potential for improving microbiome analysis accuracy within predictable ranges, and could serve as a model for addressing sequencing bias in metagenomic research.

Bacteria are associated with certain cancers and may induce genetic instability and cancer progression. The gut microbiome modulates the response to cancer therapy. Training machine learning models with response associated taxa or bacterial genes predict patients' response to immunotherapies with moderate accuracy. Clinical trials targeting the gut microbiome to improve immunotherapy efficacy have been conducted. While single bacterial strains or small consortia have not be reported yet to be successful, encouraging results have been reported in small single arm and randomized studies using transplant of fecal microbiome from cancer patients who successfully responded to therapy or from healthy volunteers.

Selenium-enriched tea represents an ideal source of selenium supplements, yet its effects on mice with intestinal disorders remain under-documented. Therefore, we have carried out relevant research.

We determined the main chemical components of selenium-enriched green tea and evaluated the antioxidant and anti-inflammatory effects of selenium-enriched green tea extract and changes in intestinal flora of antibiotic-induced intestinal disease mice through BALB/c mouse experiments.

The main chemical components of selenium-enriched green tea and green tea are significantly different. Selenium-enriched green tea is characterized by a high selenium content, with tea polyphenols, flavonoids, tea polysaccharides and catechins being the primary constituents. The results of animal experiments indicate that the extract of green tea rich in selenium increased the content of antioxidant factors in the intestines of mice and reduced the levels of intestinal inflammatory factors. This was also confirmed by mRNA gene expression determination. In addition, selenium-enriched green tea extracts can reduce the weight loss and intestinal pathological damage induced by antibiotics, promote the colonization of Bifidobacterium and Lactobacillus in the intestinal tract of mice and inhibit the growth of Escherichia coli and Enterococcus in the intestinal tract.

Selenium-enriched green tea has high nutritional content. It demonstrates superior potential in alleviating oxidative stress and inflammatory responses caused by intestinal diseases, and plays a role in regulating the intestinal flora. © 2025 Society of Chemical Industry.

The widespread use of plastic agricultural films necessitates a thorough evaluation of environmental risks posed by soil microplastics (MPs). While the intestinal tract is a critical site for MP interactions in soil organisms, current research predominantly focuses on overall physiological responses, overlooking organ-specific toxic mechanisms. To address this gap, we exposed earthworms (Eisenia fetida) to polyethylene (PE) and biodegradable polylactic acid (PLA) MPs sourced from agricultural films at an environmentally realistic concentration of 1.0 g/kg. Incorporating natural earthworm mobility, we designed two exposure scenarios: migration from clean to contaminated soil (scenario A) and vice versa (scenario B). Machine learning-driven image analysis and phenotypic profiling revealed that PE induced more severe intestinal lesions than PLA, adversely affecting intestinal immune functions. Furthermore, PE resulted in greater oxidative damage and significantly activated immune proteins such as melanin and antimicrobial peptides through reprograming immune-related gene and protein pathways. Conversely, PLA predominantly disrupted intestinal digestive and absorptive functions, though the gut microbial community partially mitigated damage through structural and compositional adaptation. Compared with scenario A, earthworms in scenario B exhibited reduced tissue damage, enhanced digestive enzyme activity, and upregulated energy-related metabolites and cell proliferation genes, indicating partial recovery from MP-induced intestinal dysfunction. These findings elucidate the distinct toxicity mechanisms of conventional and biodegradable agricultural MPs on soil organisms, while the scenario-based approach advances risk assessment by aligning experimental design with real-world ecological behaviors.

The fruit fly Drosophila melanogaster is a vital model for studying the microbiome due to the availability of genetic resources and procedures. To understand better the importance of microbial composition in shaping immune modulation, we can investigate the role of the microbiota through parasitic infection. For this, we use entomopathogenic nematodes (EPN) of the genus Steinernema which exhibit remarkable ability to efficiently infect a diverse array of insect species, facilitated by the mutualistic bacteria Xenorhabdus found within their gut. To examine the microbiome changes in D. melanogaster larvae in response to Steinernema nematode infection, D. melanogaster late second to early third instar larvae were exposed separately to S. carpocapsae and S. hermaphroditum infective juveniles. We have found that S. carpocapsae infective juveniles are more pathogenic to D. melanogaster larvae compared to the closely related S. hermaphroditum. Our microbiome analysis also indicates substantial changes in the size and composition of the D. melanogaster larval microbiome during infection with either nematode species compared to the uninfected controls. Our results serve as a foundation for future studies to elucidate the entomopathogenic-specific effector molecules that alter the D. melanogaster microbiome and understand the role of the microbiome in regulating insect anti-nematode immune processes.

The gut microbiome (GM) is implicated in human health and varies among lifestyles. So-called "traditional" diets have been suggested to promote health-associated taxa. However, most studies focused only on diets including domesticated foods. Historically, humans consumed only wild foods, which might uniquely shape GM composition. We explored the impact of a wild-food-only diet on GM, particularly whether it increases the presence of health-associated and/or "old friend" taxa, and if the alterations to GM are persistent or transient. One participant collected daily fecal samples and recorded daily food consumption over an eight-week period, the middle four weeks of which he consumed only wild foods. Samples were profiled by 16S rRNA sequencing, and oligotyping and network analysis were conducted to assess microbial co-occurrence patterns. A wild-food-only diet considerably alters the composition of the GM, and the magnitude of the changes is larger than that observed in other diet interventions. No new taxa, including "old friends" appeared; instead, the proportions of already-present taxa shifted. Network analysis revealed distinct microbial co-abundance groups restructuring across dietary phases. There is a clear successional shift from the pre-, during- and post-wild-food-only diet. This analysis highlighted structural and functional shifts in microbial interactions, underscoring diet's role in shaping the gut ecosystem.

The role of gut microbiota in human health and disease is becoming increasingly recognized. Historically, the impact of human gut microbiota on health has been studied using clinical trials and animal models. However, clinical studies often struggle with controlling variables and pinpointing disease-causing factors, while animal models fall short of accurately replicating the human gut environment. Additionally, continuous sample collection for gut microbiota analysis in vivo presents significant ethical and technical challenges. To address these limitations, in vitro fermentation models have emerged as promising alternatives. These models aim to simulate the structural and functional characteristics of the human gut in a controlled setting, offering valuable insights into microbial behavior. This review highlights current knowledge and technological advances in in vitro cultivation systems for human gut microbiota, focusing on key elements such as three-dimensional scaffolds, culture media, fermentation systems, and analytical techniques. By examining these components, the review establishes a framework for improving methods to cultivate and study human gut microbiota, enhancing research methodologies for better understanding microbial interactions, behavior, and adaptation in diverse environments.

Growing evidence suggests that microbes located within the gastrointestinal tract and other anatomical locations influence the development and progression of diseases such as cancer.

Clinical and preclinical evidence suggests that microbes in the gastrointestinal tract and other anatomical locations, such as the respiratory tract, may affect carcinogenesis, development of metastases, cancer treatment response, and cancer treatment-related adverse effects. Within tumors of patients with cancer, microbes may affect response to treatment, and therapies that reduce or eliminate these microbes may improve outcomes in patients with cancer. Modulating gastrointestinal tract (gut) microbes through fecal microbiota transplant and other strategies such as dietary intervention (eg, high-fiber diet intervention) has improved outcomes in small studies of patients treated with cancer immunotherapy. In contrast, disruption of the gut microbiota by receipt of broad-spectrum antibiotics prior to treatment with cancer immunotherapy has been associated with poorer overall survival and higher rates of adverse effects in patients treated with immune checkpoint blockade for solid tumors and also with chimeric antigen receptor T-cell therapy for hematologic malignancies.

Microbes in the gut and other locations in the body may influence the development and progression of cancer and may affect the response to adverse effects from cancer therapy. Future therapies targeting microbes in the gut and other locations in the body could potentially improve outcomes in patients with cancer.

Jellyfish blooms have significant ecological and economic impacts, yet the microbial communities associated with these blooms remain poorly understood, despite their potential influence on host fitness and microbial communities in the surrounding water. In this study, we explored temporal and tissue-specific variations in the microbiota of Rhopilema nomadica, the dominant jellyfish species in the Eastern Mediterranean Sea, across winter and summer blooms. During late summer blooms, microbial richness declined, coinciding with an increase in Endozoicomonas and unclassified Rickettsiales, while Tenacibaculum predominantly characterized winter blooms. Tissue-specific analyses revealed bacterial groups that were more consistently associated with different jellyfish tissues (e.g., Bacteroides in the bell and Simkaniaceae in the gonads), suggesting different microbial niches within the host. Furthermore, some key bacteria associated with R. nomadica, including Endozoicomonas, unclassified Rickettsiales, and Bacteroides were detected in the surrounding bloom water but absent from remote seawater, suggesting potential localized transmission dynamics between jellyfish and their immediate marine environment. Finally, a comparative analysis with nine additional jellyfish species identified recurring microbial taxa, including Endozoicomonas, Mycoplasma, and Spiroplasma, though no universal core microbiota was observed. This study represents the first exploration of microbial dynamics within R. nomadica blooms and the most comprehensive analysis of jellyfish-associated microbiomes across bloom stages and tissues to date. Our findings reveal complex relationships between jellyfish species, bloom progression, their microbial communities, and the surrounding seawater.

Cow milk contains essential nutrients, with β-casein existing in A1 and A2 forms. Studies suggest that A2 milk (containing only A2 β-casein) may offer gastrointestinal (GI) benefits compared to A1/A2 milk (containing both forms). This study investigated the effects of A2 milk consumption on the gut microbiota of South Korean cohort experiencing GI discomfort after consuming A1/A2 milk. Thirty-five participants with GI discomfort after milk consumption were included. Stool DNA was analyzed using 16S rRNA gene sequencing before and after consuming either A1/A2 or A2 milk. Beta diversity analysis using the generalized UniFrac distance method revealed a significant shift in gut microbiota composition after A2 milk consumption (p = 0.04), but no significant change after consuming A1/A2 milk. Significant differences in gut microbiota composition were found between A1/A2 and A2 milk drinkers after milk consumption (p = 0.031). Alpha diversity indices remained unchanged. Notable increases in beneficial microbes, including Bifidobacterium and Blautia, were observed after A2 milk intake. Linear discriminant analysis Effect Size (LEfSe) analysis identified significant enrichment of Actinobacteria, particularly Bifidobacterium longum and Blautia wexlerae, in the A2 group. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis highlighted enriched transport systems related to energy, peptides, sugars, and raffinose family oligosaccharides in the A2 group. Spearman correlation showed significant associations between Bifidobacterium, Blautia, and enhanced transport systems exclusively in the A2 group. Two weeks of A2 milk consumption led to significant alterations in gut microbiota, promoting beneficial microbes and related functions. A2 milk could be a suitable alternative for subjects who experience milk-intake-related GI discomfort.

The importance of the microbiome, particularly the gut microbiota and its implications for health, is well established. However, an increasing number of studies further strengthen the link between an imbalanced gut microbiota and a greater predisposition to different diseases. The gut microbiota constitutes a fundamental ecosystem for maintaining human health. Its alteration, known as dysbiosis, is associated with a wide range of conditions, including intestinal, metabolic, immunological, or neurological pathologies, among others. In recent years, there has been a substantial increase in knowledge about probiotics-bacterial species that enhance health or address various diseases-with numerous studies reporting their benefits in preventing or improving these conditions. This review aims to analyze the most common pathologies resulting from an imbalance in the gut microbiota, as well as detail the most important and known gut probiotics, their functions, and mechanisms of action in relation to these conditions.

This chapter examines how human biology and microbial "secondary genomes" have co-evolved to shape neurodevelopment through the gut-brain axis. Microbial communities generate metabolites that cross blood-brain and placental barriers, influencing synaptogenesis, immune responses, and neural circuit formation. Simultaneously, Human Accelerated Regions (HARs) and Endogenous Retroviruses (ERVs) modulate gene expression and immune pathways, determining which microbes thrive in the gut and impacting brain maturation. These factors converge to form a dynamic host-microbe dialogue with significant consequences for neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia. Building on evolutionary perspectives, the chapter elucidates how genetic and immune mechanisms orchestrate beneficial and pathological host-microbe interactions in early brain development. It then explores therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation, and CRISPR-driven microbial engineering, targeting gut dysbiosis to mitigate or prevent neurodevelopmental dysfunctions. Furthermore, innovative organ-on-chip models reveal mechanistic insights under physiologically relevant conditions, offering a translational bridge between in vitro experiments and clinical applications. As the field continues to evolve, this work underscores the translational potential of manipulating the microbiome to optimize neurological outcomes. It enriches our understanding of the intricate evolutionary interplay between host genomes and the microbial world.

Dysbiosis, characterized by a microbial imbalance, particularly within the gut microbiota, has emerged as a significant health concern linked to various diseases. This study analyzed 8097 patent documents from The Lens database (2005-2024) to examine global innovation trends in dysbiosis management. The patent filings showed exponential growth, peaking at 1222 documents in 2022, with the United States leading in publications (4361 documents). The analysis revealed three primary innovation clusters: bacterial-based therapeutics (44.8% of patents), specific therapeutic applications (27.6%), and diagnostic methods (15.9%). The disease associations predominantly included inflammatory conditions, infections, and cancer. The patent classifications highlighted a significant focus on probiotic development and microbiota modulation. The surge in patent activity since 2014 correlates with advances in DNA sequencing technology and the growing recognition of dysbiosis's role in human health. This analysis provides valuable insights into the evolving landscape of microbiome therapeutics and future directions for dysbiosis management.

Whole-brain radiotherapy (WBRT) is an important way to treat multiple metastases. Ultra-high dose rate (FLASH) can avoid neurotoxicity caused by conventional irradiation, it has attracted much attention. This study aims to study the difference of irradiation-induced intestinal flora between conventional dose rate and FLASH WBRT.

WBRT with 10 Gy was performed with electron-beam conventional irradiation (2 Gy/s) and electron-beam FLASH (eFLASH) irradiation (230 Gy/s). The intestinal feces and whole brain of mice were isolated after behavioral evaluation at 1st, 3rd and 10th weeks post-irradiation. HE staining and immunofluorescence were used to access the level of brain damage. The differences in intestinal microbes and transcription levels were detected by 16S rRNA gene sequencing and transcriptome sequencing, respectively.

eFLASH irradiation significantly reduced radiation neurotoxicity and had a long-term protective effect on cognitive function and learning and memory ability. Compared with conventional irradiation, eFLASH irradiation not only up-regulated the expression of genes related to neuronal regeneration and digestive system, but also induced more abundant intestinal microflora, especially the "probiotics" such as Lachnospiraceae and others, which were proved to play a role in radiation protection, increased significantly after eFLASH irradiation. The up-regulated microbiota after eFLASH irradiation was significantly positively correlated with genes related to neuronal development and regeneration, while significantly negatively correlated with genes related to inhibitory synapses. Additionally, conventional irradiation down-regulated microbial metabolism-related pathways, while FLASH did not.

In summary, we explored the unique gut microbiota changes induced by eFLASH WBRT for the first time, providing a theoretical basis for exploring the mechanism of action of FLASH.

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

Esophageal cancer (EC) ranks among the most prevalent cancers worldwide, with a particularly high incidence in the Asian population. Due to the inconspicuous nature of early symptoms, patients with esophageal cancer are typically diagnosed in the middle to late stages, resulting in suboptimal overall treatment outcomes. Consequently, there is an urgent need to explore and refine therapeutic strategies. Microorganisms have been identified in numerous tumor tissues, including EC, and these microorganisms are referred to as the intratumoral microbiome. Intratumoral microbiota and their metabolic byproducts can influence the progression and treatment of esophageal cancer through various mechanisms, such as modulating tumor cell metabolism and local immune responses. Therefore, the intratumoral microbiota may potentially serve as a target for the treatment of esophageal cancer. This review delineates the composition, origin, and diagnostic significance of intratumoral microbiota in esophageal cancer tissue, and discusses the mechanisms by which intratumoral microbiota contribute to the onset of esophageal cancer. In addition, the impact of intratumoral microbiota on the treatment of esophageal cancer and its intervention measures are also addressed.

We use open source human gut microbiome data to learn a microbial "language" model by adapting techniques from Natural Language Processing (NLP). Our microbial "language" model is trained in a self-supervised fashion (i.e., without additional external labels) to capture the interactions among different microbial taxa and the common compositional patterns in microbial communities. The learned model produces contextualized taxon representations that allow a single microbial taxon to be represented differently according to the specific microbial environment in which it appears. The model further provides a sample representation by collectively interpreting different microbial taxa in the sample and their interactions as a whole. We demonstrate that, while our sample representation performs comparably to baseline models in in-domain prediction tasks such as predicting Irritable Bowel Disease (IBD) and diet patterns, it significantly outperforms them when generalizing to test data from independent studies, even in the presence of substantial distribution shifts. Through a variety of analyses, we further show that the pre-trained, context-sensitive embedding captures meaningful biological information, including taxonomic relationships, correlations with biological pathways, and relevance to IBD expression, despite the model never being explicitly exposed to such signals.

Cardiovascular diseases (CVDs), including heart failure (HF), hypertension, myocardial infarction (MI), and atherosclerosis, are increasingly linked to gut microbiota dysbiosis and its metabolic byproducts. HF, affecting over 64 million individuals globally, is associated with systemic inflammation and gut barrier dysfunction, exacerbating disease progression. Similarly, hypertension and MI correlate with reduced microbial diversity and an abundance of pro-inflammatory bacteria, contributing to vascular inflammation and increased cardiovascular risk. Atherosclerosis is also influenced by gut dysbiosis, with key microbial metabolites such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs) playing crucial roles in disease pathogenesis. Emerging evidence highlights the therapeutic potential of natural compounds, including flavonoids, omega-3 fatty acids, resveratrol, curcumin, and marine-derived bioactives, which modulate the gut microbiota and confer cardioprotective effects. These insights underscore the gut microbiota as a critical regulator of cardiovascular health, suggesting that targeting dysbiosis may offer novel preventive and therapeutic strategies. Further research is needed to elucidate underlying mechanisms and optimize microbiome-based interventions for improved cardiovascular outcomes.

Laryngeal cancer incidence is rising globally; the role of gut microbiota remains underexplored. This study aimed to establish a causal link between gut microbiota and laryngeal cancer to inform preventive and therapeutic strategies.

Gut microbiota data from GWAS conducted by the MiBioGen consortium served as the exposure variable, with laryngeal cancer as the outcome variable. the exposure variable and the outcome variable were analyzed using Mendelian Randomization. The primary method was Inverse Variance Weighted analysis, with heterogeneity and pleiotropy assessed through Cochran's Q test, MR-Egger regression, and MR-PRESSO.

In the study, we identified five bacterial taxa with potential causal relationships with laryngeal cancer risk: Higher levels of Clostridiaceae1 (OR = 0.9993, 95% CI 0.9986-0.9999, p = 0.0463) and Turicibacter (OR = 0.9995, 95% CI 0.9989-0.9999, p = 0.0384) were linked to reduced cancer risk, while Mollicutes RF9 (OR = 1.0010, 95% CI 1.0003-1.0016, p = 0.0027), Euryarchaeota (OR = 1.0004, 95% CI 1.0001-1.0007, p = 0.0234), and Cyanobacteria (OR = 1.0005, 95% CI 1.0000-1.0009, p = 0.0464) were associated with increased risk.

Our findings suggest a causal relationship between gut microbiota composition and laryngeal cancer risk. Clostridiaceae1 and Turicibacter may play a protective role, while Mollicutes RF9, Euryarchaeota, and Cyanobacteria could contribute to increased cancer susceptibility. These insights highlight potential microbiome-based strategies for early detection, prevention, and therapeutic intervention in laryngeal cancer.

Level 5.

A growing body of evidence supports the potential role of the oral microbiota in influencing cognitive function. Centenarians, at the extreme end of the lifespan, are the ideal cohort to study the long-term effects of inflammaging.

Twenty-three centenarians were examined by a neurologist, neuropsychologist and dentist to assess cognitive status and oral health. They were also profiled for oral microbiota and inflammasome.

We found less alpha diversity in the oral microbiota of participants with dementia and an overall depletion of typical oral commensals, including Alloprevotella, Prevotella, Veillonella, Fusobacterium and Leptotrichia. The latter two were also underrepresented in edentulous compared with dentate subjects. Moreover, levels of pro-inflammatory cytokines and chemokines tended to be higher in participants with dementia.

Our data support a relationship between oral microbiota, cognitive status and inflammation, which deserves further exploration to counteract cognitive decline while promoting healthy aging.

The gut microbiome contributes to chronic inflammatory responses in ulcerative colitis (UC), but molecular mechanisms and disease-relevant effectors remain unclear. Here we analyze the pro-inflammatory properties of colonic fluid obtained during colonoscopy from UC and control patients. In patients with UC, we find that the pelletable effector fraction is composed mostly of bacterial extracellular vesicles (BEVs) that exhibit high IgA-levels and incite strong pro-inflammatory responses in IgA receptor-positive (CD89+) immune cells. Biopsy analyses reveal higher infiltration of CD89+ immune cells in the colonic mucosa from patients with UC than control individuals. Further studies show that IgA-coated BEVs, but not host-derived vesicles nor soluble IgA, are potent activators of pro-inflammatory responses in CD89+ cells. IgA-coated BEVs also exacerbate intestinal inflammation in a dextran sodium sulfate colitis model using transgenic mice expressing human CD89. Our data thus implicate a link between IgA-coated BEVs and intestinal inflammation via CD89+ immune cells, and also hint a potential new therapeutic target for UC.

Background/Objectives: Alginate and its oligosaccharides (AOS) are widely used in the food industry all over the world. However, how they are fermented by the human gut microbiota has not been fully elucidated. Here, we aim to explore the structure-property relationships of the fermentation of these carbohydrates by the human gut microbiota. Methods: High-performance liquid chromatography, 16S rRNA gene amplicon high-throughput sequencing, whole genome sequencing, and metabolome analysis were used to study the fermentation of alginate and AOS by the human gut microbiota. Results and Conclusions: Low-molecular-weight alginate and AOS were more fermentable than alginate. Moreover, fermentation of AOS with a molecular weight (Mw) of 0.8 kDa produced higher amounts of acetate and butyrate than that with a Mw of 0.3 kDa. B. xylanisolvens was a keystone species responsible for the fermentation. Additionally, each B. xylanisolvens strain was characterized with a unique capability for AOS fermentation. Specifically, B. xylanisolvens P19-10, a bacterium isolated from healthy human colon, exhibited the best fermentation capacity. Genomic analysis suggested that B. xylanisolvens P19-10 was armed with a plethora of carbohydrate-active enzymes. Additionally, the polysaccharide lyase family 6_1 was identified as a candidate enzyme responsible for the utilization of AOS. Moreover, fermentation of AOS by B. xylanisolvens P19-10 was associated with significant changes in bacterial metabolites and metabolic pathways. Future perspectives: Our study provides novel mechanistic insights into the fermentation of alginate and AOS by human gut microbiota, which has applications for the development of new carbohydrate-based nutraceuticals and foods.

Many studies indicate the gut microbiome is associated with diseases caused by administering high-dose glucocorticoids (GCs), such as hypertension, hyperglycemia, and osteoporosis. However, the association between intestinal flora and the use of high-dose GCs remains elusive. We aimed to characterize gut microbiome in Graves' ophthalmopathy (GO) patients after administering high-dose GCs. In this study, 20 primary GO patients were recruited. The differences in gut microbiota of GO patients before and after administering high-dose GCs were analyzed by 16S rDNA sequencing technology. Untargeted metabolomic analysis was used to examine the differences in gut metabolites between two groups. There were significant differences in α and β diversities of gut microbiota in GO patients before and after administering high-dose GCs. The random forest analysis indicated that three intestinal bacteria (Faecalibacterium, Streptococcus, and Prevotella) could distinguish the two groups with the highest accuracy, which was proven by receiver operator characteristic curve and linear discriminant analysis effect size analysis. The short-chain fatty acid-producing ability in GO patients' gut after high-dose GC administration was significantly decreased. The 5-hydroxytryptamine levels significantly increased in the gut of GO patients after administering high-dose GCs. Our study suggests that high-dose GC administration causes the changes in gut microbiome and metabolites. Moreover, the altered flora and metabolites are related to hypertension, hyperglycemia, and osteoporosis. These findings can help understand the development of side effects caused by high-dose GCs and can be further used to develop potential probiotics to facilitate the prevention for those side effects.IMPORTANCEFor the first time, we revealed that gut microbiome and metabolome in Graves' ophthalmopathy patients after high-dose glucocorticoid (GC) administration significantly changed, and the altered flora and metabolites are related to hypertension, hyperglycemia, and osteoporosis. These findings can help understand the development of side effects caused by high-dose GCs and can be further used to develop potential probiotics to facilitate the prevention for those side effects.

This systematic review aims to synthesize key empirical findings to understand how various elements of the built environment influence the microbiome concerning children's health and well-being. A comprehensive literature search was conducted across multiple databases, focusing on studies that examined the relationship between built environment factors and the microbiome aspects of childhood. A total of 42 studies were included in the final systematic review. We analyzed these studies from a range of different lenses, starting with basic research questions and variables to types of built environments, age groups of children, sampling strategy, bioinformatics, and the biological methods utilized. This review highlights a growing emphasis on children's exposure to nature within built environments and its potential to beneficially alter the microbiome, with 38% of studies addressing this link. It also identifies a significant research gap in connecting built environment design features (landscape and/or architectural) to microbiome outcomes and associated health, behavioral, and mental health impacts on children. The findings indicate that interventions aimed at improving the built environment quality via design could foster healthier microbiomes in children's environments. This review underscores the need for interdisciplinary research and policy initiatives that integrate microbiome science with built environment design to promote children's health and well-being.

Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.