Dietary fiber interventions to modulate the gut microbiota have largely relied on isolated fibers or specific fiber sources. We hypothesized that fibers systematically blended could promote more health-related bacterial groups. Initially, pooled in vitro fecal fermentations were used to design dietary fiber mixtures to support complementary microbial groups related to health. Then, microbial responses were compared for the designed mixtures versus their single fiber components in vitro using fecal samples from a separate cohort of 10 healthy adults. The designed fiber mixtures outperformed individual fibers in supporting bacterial taxa across donors resulting in superior alpha diversity and unexpected higher SCFA production. Moreover, unique shifts in community structure and specific taxa were observed for fiber mixtures that were not observed for single fibers, suggesting a synergistic effect when certain fibers are put together. Fiber mixture responses were remarkably more consistent than individual fibers across donors in promoting several taxa, especially butyrate producers from the Clostridium cluster XIVa. This is the first demonstration of synergistic fiber interactions for superior support of a diverse group of important beneficial microbes consistent across people, and unexpectedly high SCFA production. Overall, harnessing the synergistic potential of designed fiber mixtures represents a promising and more efficacious avenue for future prebiotic development.

IgA-coated fractions of the intestinal microbiota of Crohn's disease (CD) patients have been shown to contain taxa that hallmark the compositional dysbiosis in CD microbiomes. However, the correlation between other cellular properties of intestinal bacteria and disease has not been explored further, especially for features that are not directly driven by the host immune-system, e.g. the expression of surface sugars by bacteria. By sorting and sequencing IgA-coated and lectin-stained fractions from CD patients microbiota and healthy controls, we found that lectin-stained bacteria were distinct from IgA-coated bacteria, but still displayed specific differences between CD and healthy controls. To exploit the discriminatory potential of both, immunoglobulin coated bacteria and the altered surface sugar expression of bacteria in CD, we developed a multiplexed single cell-based analysis approach for intestinal microbiota. By multi-parameter microbiota flow cytometry (mMFC) we characterized the intestinal microbiota of 55 CD patients and 44 healthy controls for 11-parameters in total, comprising host-immunoglobulin coating and the presence of distinct surface sugar moieties. The data were analyzed by machine-learning to assess disease-specific marker patterns in the microbiota phenotype. mMFC captured detailed characteristics of CD microbiota and identified patterns to classify CD patients. In addition, we identified phenotypic signatures in the CD microbiota which not only reflected remission after 6 weeks of anti-TNF treatment, but were also able to predict remission before the start of an adalimumab treatment course in a pilot study. We here present the proof-of-concept demonstrating that multi-parameter single-cell bacterial phenotyping by mMFC could be a novel tool with high translational potential to expand current microbiome investigations by phenotyping of bacteria to identify disease- and therapy-associated cellular alterations and to reveal novel target properties of bacteria for functional assays and therapeutic approaches.

Liver cancer is usually diagnosed at an advanced stage and is the third most common cause of cancer-related death worldwide. In addition to the lack of effective treatment options, resistance to therapeutic drugs is a major clinical challenge. The gut microbiota has recently been recognized as one of the key factors regulating host health. The microbiota and its metabolites can directly or indirectly regulate gene expression in the liver, leading to gut-liver axis dysregulation, which is closely related to liver cancer occurrence and the treatment response. Gut microbiota disturbance may participate in tumor progression and drug resistance through metabolite production, gene transfer, immune regulation, and other mechanisms. However, systematic reviews on the role of the gut microbiota in drug resistance in liver cancer are lacking. Herein, we review the relationships between the gut microbiota and the occurrence and drug resistance of hepatocellular carcinoma, summarize the emerging mechanisms underlying gut microbiota-mediated drug resistance, and propose new personalized treatment options to overcome this resistance.

The probiotic impact of microbes on host metabolism and health depends on both host genetics and bacterial genomic variation. Faecalibacterium prausnitzii is the predominant human gut commensal emerging as a next-generation probiotic. Although this bacterium exhibits substantial intraspecies diversity, it is unclear whether genetically distinct F. prausnitzii strains might lead to functional differences in the gut microbiome. Here, we isolated and characterized a novel F. prausnitzii strain (UT1) that belongs to the most prevalent but underappreciated phylogenetic clade in the global human population. Genome analysis showed that this butyrate-producing isolate carries multiple putative mobile genetic elements, a clade-specific defense system, and a range of carbohydrate catabolic enzymes. Multiomic approaches were used to profile the impact of UT1 on the gut microbiome and associated metabolic activity of C57BL/6 mice at homeostasis. Both 16S rRNA and metagenomic sequencing demonstrated that oral administration of UT1 resulted in profound microbial compositional changes including a significant enrichment of Lactobacillus, Bifidobacterium, and Turicibacter. Functional profiling of the fecal metagenomes revealed a markedly higher abundance of carbohydrate-active enzymes (CAZymes) in UT1-gavaged mice. Accordingly, UT1-conditioned microbiota possessed the elevated capability of utilizing starch in vitro and exhibited a lower availability of microbiota-accessible carbohydrates in the gut. Further analysis uncovered a functional network wherein UT1 reduced the abundance of mucin-degrading CAZymes and microbes, which correlated with a concomitant reduction of fecal mucin glycans. Collectively, our results reveal a crucial role of UT1 in facilitating the carbohydrate metabolism of the gut microbiome and expand our understanding of the genetic and phenotypic diversity of F. prausnitzii.

In health, the gut microbiome functions as a stable ecosystem maintaining overall balance and ensuring its own survival against environmental stressors through complex microbial interaction. This balance and protection from stressors is maintained through interactions both within the bacterial ecosystem as well as with its host. As a consequence, the gut microbiome plays a critical role in various physiological processes including maintaining the structure and function of the gut barrier, educating the gut immune system, and modulating the gut motor, digestive/absorptive, as well as neuroendocrine system all of which are crucial for human health and disease pathogenesis. Pre- and probiotics, widely available and clinically established, offer various health benefits primarily by beneficially modulating the gut microbiome. However, their clinical outcomes can vary significantly due to differences in host physiology, diets, individual microbiome compositions, and other environmental factors. This perspective paper highlights emerging scientific insights into the importance of microbial micronutrient sharing, gut redox balance, keystone species, and the gut barrier in maintaining a diverse and functional microbial ecosystem, and their relevance to human health. We propose a novel approach that targets microbial ecosystems and keystone taxa performance by supplying microbial micronutrients in the form of colon-delivered vitamins, and precision prebiotics [e.g. human milk oligosaccharides (HMOs) or synthetic glycans] as components of precisely tailored ingredient combinations to optimize human health. Such a strategy may effectively support and stabilize microbial ecosystems, providing a more robust and consistent approach across various individuals and environmental conditions, thus, overcoming the limitations of current single biotic solutions.

The COVID-19 pandemic highlighted the potential of peptide-based therapies as an alternative to traditional pharmaceutical treatments for SARS-CoV-2 and its variants. Our review explores the role of therapeutic peptides in modulating immune responses, inhibiting viral entry, and disrupting replication. Despite challenges such as stability, bioavailability, and the rapid mutation of the virus, ongoing research and clinical trials show that peptide-based treatments are increasingly becoming integral to future viral outbreak responses. Advancements in computational modelling methods in combination with artificial intelligence will enable mass screening of therapeutic peptides and thereby, comprehending a peptide repurposing strategy similar to the small molecule repurposing. These findings suggest that peptide-based therapies play a critical and promising role in future pandemic preparedness and outbreak management.

Combining brachytherapy with immunotherapies, particularly immune checkpoint inhibitors (ICIs), is a promising approach for potentiating both local control of the tumor and fully exploiting the synergies between pharmaceutic immunomodulation and radiotherapy. Compared to other radiotherapy techniques, BT has a potential to better spare lymphatic drainage areas and gut microbiota, thus reducing the immunosuppressive effects of radiation therapy. In addition, it delivers a broad range of doses due to inherent dose inhomogeneity within the implanted volume. This variability increases the probability that immune infiltrates would be activated, particularly since the optimal dose for immune activation is not yet firmly established. Even if preclinical models show that radiotherapy can stimulate immune responses, it can also induce toxic effects on immune effectors and combination trials show conflicting outcomes. There is a need for refining radiation modalities to enhance immune potentiation. The dosimetric specificities of BT may offer various advantages and should be explored further. Scarce clinical data on combining brachytherapy with ICIs in advanced cancer suggest potential benefits, with case reports of complete local responses and abscopal effects. However, validation requires a large number of patients in randomized clinical trials for which ideal design is discussed. In parallel with ongoing clinical developments, there is a need to refine preclinical models in order to better analyze the specific biological effects involved in BT, in light of immunomodulatory systemic treatments.

The gut microbiota is a key modulator of human health and the status of major diseases including cancer, diabetes and inflammatory bowel disease. Central to microbiota survival is the ability to metabolise complex dietary and host-derived glycans, including intestinal mucins. The prominent human gut microbe Bacteroides thetaiotaomicron (B. theta) is a versatile and highly efficient complex glycan degrader thanks to the expansion of gene clusters termed polysaccharide utilisation loci (PULs). While the mechanism of action for several singular dietary glycan-induced PULs have been elucidated, studies on the unusually high number of mucin-inducible PULs in B. theta significantly lag behind. Here we show that a mucin inducible PUL BT4240-50 encodes activities consistent with the processing and metabolism of mucin O-glycoproteins and their core sugar N-acetylgalactosamine (GalNAc). PUL BT4240-50 was also shown to be important for competitive growth on mucins in vitro, encoding a kinase (BT4240) critical for GalNAc metabolism. Additionally, BT4240-kinase was shown to be essential for glycosaminoglycan metabolism, extending the PULs function beyond mucins. These data advance our understanding of glycoprotein metabolism at mucosal surfaces, highlighting GalNAc as a key metabolite for competitive microbial survival in the human gut.

Despite explosive rise in allergies, little is known about early life gut microbiota effects on postnatal respiratory function. We hypothesized that Enterobacteriaceae-dominant gut microbiota from eczemic infants increases Type 2 inflammation and decreases lung function in transplanted mice, while Bacteroidaceae-dominant gut microbiota from non-eczemic infants is protective. Fecal microbiota transplants (FMT) from eczemic infants "Infant A" and non-eczemic infants "Infant B" were successfully transplanted into germ-free C57BL/6 mice, passing to offspring unchanged. Infant A and B, Adult C-human-derived (positive control), and Mouse (negative control) microbiotas all in C57BL/6 mice were tested for effects on airway function in nonallergic (phosphate-buffered saline [PBS]) and allergic (house dust mite [HDM]) conditions. Baseline lung mechanics in mice with human microbiotas (HUmicrobiota) were significantly impaired compared to Mouse microbiota controls (MOmicrobiota) with or without HDM; respiratory system resistance (Rrs) was increased (P < 0.05-P < 0.01), and respiratory system compliance (Crs) was decreased (P < 0.05-P < 0.01). HUMicrobiota mice showed a statistically significant impairment compared to MOmicrobiota mice in lung parameters Rrs, Ers, Rn, and G at baseline, and at multiple methacholine (MCh) doses with baseline removed. Impairment manifested as increased small airway resistance and tissue resistance. HDM significantly elevated IL-4, eosinophils, lung inflammation, and mucus cell metaplasia, and decreased macrophages and lung function (P < 0.05) in mice of all microbiotas, yet each HUmicrobiota produced distinct features. Infant B and Adult C mice had elevated basal levels of total IgE compared to MOmicrobiota and Infant A mice (P < 0.05). In HUmicrobiota mice given HDM, only Adult C had elevated IL-5 and IL-13 (P < 0.05), only Adult C and Infant B mice had elevated neutrophils (P < 0.05), and only Infant A had elevated lymphocytes (P < 0.01).

Fecal microbiota transplants (FMT) of three distinct human communities to germ-free mice exacerbated inflammation and decreased lung function in their offspring. Taxa formerly described to induce an allergic response (agonists) and pro-inflammatory taxa were abundant in HUmicrobiotas compared to MOmicrobiota controls, while taxa formerly described to reduce allergic responses (antagonists) and anti-inflammatory taxa were numerous in MOmicrobiotas and low in HUmicrobiotas. Thus, we largely rejected our hypotheses because data supported multiple pro-inflammatory allergy agonists functioning in a community-wide fashion to impair lung function in the absence of antagonistic anti-inflammatory taxa. Structure of HUmicrobiotas played a key role in determining varied allergic responses and resulting lung impairment, yet, strikingly, all mice with HUmicrobiotas had impaired lung function even in the absence of allergens. Using a comparative approach, we showed that composition of gut microbiota can alter innate/immune regulation in the gut-lung axis to increase baseline lung function responses and the risk of allergic sensitization.

Live biotherapeutic products (LBPs) are biological products composed of living micro-organisms, developed to prevent, treat, or cure diseases. Examples include cultured strains of Akkermansia muciniphila and Christensenella minuta, as well as treatments using purified Firmicutes spores for recurrent Clostridioides difficile infections. There is a need for guidelines over the increasing interest in developing LBPs. A panel of microbiome experts from Asia-Pacific countries articulates their perspectives on key considerations for LBP development.

Experts in microbiome research, microbiology, gastroenterology, internal medicine and biotherapeutics industry were invited to form a panel. During the 2023 Inauguration Conference of the Asia-Pacific Microbiota Consortium, an organised, iterative roundtable discussion was conducted to build expert consensus on critical issues surrounding the development of LBP.

The consensus statements were organised into three main aspects: (a) rationales of LBP development, (b) preclinical studies and (c) preparation for clinical studies. The panel strongly recommended to prioritise human-derived and food-sourced strains for development, with indications based on clinical need and efficacy shown in studies. Preclinical evaluation should involve thorough screening, genotyping and phenotyping, as well as comprehensive in vitro and animal studies to assess functional mechanisms and microbiological safety. Rigorous cell banking practices and genetic monitoring are essential to ensure product consistency and safety throughout the manufacturing process. Clinical trials, including postmarketing surveillance, must be carefully designed and closely monitored, with robust safety and risk management protocols in place.

The development of LBP should be approached with a strong emphasis on microbiological evaluation, clinical relevance, scientific mechanisms and safety at every stage. These measures are essential to ensure the safety, effectiveness and long-term success of the product.

The gut and lung microbiomes play crucial roles in host defense and mayserve as predictive markersfor clinical outcomes in critically ill patients. Despite this, the simultaneous dynamics of lung and gut microbiomes during critical illness remain unclear. This study aims to assess the longitudinal changes in lung and gut microbiota among mechanically ventilated ICU patients with and without infection and to identify microbial features predictive of clinical outcomes, including the development of ventilator associated pneumonia (VAP).

In this prospective observational study, we analyzed 73 endotracheal aspirates (ETA) and 93 rectal swabs collected from 38 ICU patients over multiple timepoints (intubation, infection onset, post-antibiotic, and extubation/discharge). Patients were categorized into three groups: (1) VAP, (2) other infections, and (3) uninfected controls. Lung and gut microbiota were characterized using 16S rRNA gene sequencing. Primary outcomes included microbial diversity and community composition; secondary outcomes included ICU length of stay and ventilator-free days.

Alpha diversity declined more significantly in infected patients than in controls during the ICU stay, with the most pronounced changes in lung microbiota. We found an enrichment of Enterobacteriaceae and other Proteobacteria in the lung microbiome of pneumonia patients, while the gut microbiota remained relatively stable. Relative abundances of key taxa such as Mogibacterium were associated with mechanical ventilation duration.

This study reveals that distinct microbial patterns in both lung and gut microbiota are associated with infection and clinical outcomes in critically ill patients. Understanding these dynamics is crucial for developing targeted microbiota interventions, potentially improving outcomes such as VAP prevention and management.

Ethics Committee of Canton Vaud, Switzerland (2017-01820).

The human gut microbiome is most dynamic in early life. Although sweeping changes in taxonomic architecture are well described, it remains unknown how, and to what extent, individual strains colonize and persist and how selective pressures define their genomic architecture. In this study, we combined shotgun sequencing of 1,203 stool samples from 26 mothers and their twins (52 infants), sampled from childbirth to 8 years after birth, with culture-enhanced, deep short-read and long-read stool sequencing from a subset of 10 twins (20 infants) to define transmission, persistence and evolutionary trajectories of gut species from infancy to middle childhood. We constructed 3,995 strain-resolved metagenome-assembled genomes across 399 taxa, and we found that 27.4% persist within individuals. We identified 726 strains shared within families, with Bacteroidales, Oscillospiraceae and Lachnospiraceae, but not Bifidobacteriaceae, vertically transferred. Lastly, we identified weaning as a critical inflection point that accelerates bacterial mutation rates and separates functional profiles of genes accruing mutations.

Although disturbances in the gut microbiome have been implicated in multiple sclerosis (MS), little is known about the changes and interactions between the gut microbiome and blood metabolome, and how these changes affect disease-modifying therapy (DMT) in preventing the progression of MS. In this study, the structure and composition of the gut microbiota were evaluated using 16S rRNA gene sequencing and an untargeted metabolomics approach was used to compare the serum metabolite profiles from patients with relapsing-remitting MS (RRMS) and healthy controls (HCs). Results indicated that RRMS was characterized by phase-dependent α-phylogenetic diversity and significant disturbances in serum glycerophospholipid metabolism. Notably, α-phylogenetic diversity was significantly decreased in RRMS patients during the chronic phase (CMS) compared with those in the acute phase (AMS). A distinctive combination of two elevated genera (Slackia, Lactobacillus) and five glycerophospholipid metabolism-associated metabolites (four increased: GPCho(22:5/20:3), PC(18:2(9Z,12Z)/16:0), PE(16:0/18:2(9Z,12Z)), PE(18:1(11Z)/18:2(9Z,12Z)); one decreased: PS(15:0/22:1(13Z))) in RRMS patients when comparing to HCs. Moreover, a biomarker panel consisting of four microbial genera (three decreased: Lysinibacillus, Parabacteroides, UBA1819; one increased: Lachnoanaerobaculum) and two glycerophospholipid metabolism-associated metabolites (one increased: PE(P-16:0/22:6); one decreased: CL(i-12:0/i-16:0/i-17:0/i-12:0)) effectively discriminated CMS patients from AMS patients, which indicate correlation with higher disability. Additionally, DMTs appeared to attenuate MS progression by reducing UBA1819 and upregulating CL(i-12:0/i-16:0/i-17:0/i-12:0). These findings expand our understanding of the microbiome and metabolome roles in RRMS and may contribute to identifying novel diagnostic biomarkers and promising therapeutic targets.

Diet can impact host health through changes to the gut microbiota, yet we lack mechanistic understanding linking nutrient availability and microbiota composition. Here, we use thousands of microbial communities cultured in vitro from human stool to develop a predictive model of community composition upon addition of single nutrients from central carbon metabolism to a complex medium. Among these communities, membership was largely determined by the donor stool, whereas relative abundances were determined by the supplemental carbon source. The absolute abundance of most taxa was independent of the supplementing nutrient due to the ability of a few organisms to quickly exhaust their niche in the complex medium and then exploit and monopolize the supplemental carbon source. Relative abundances of dominant taxa could be predicted from the nutritional preferences and growth dynamics of species in isolation, and exceptions were consistent with strain-level variation in growth capabilities. Our study reveals that assembly of this community of gut commensals can be explained by nutrient utilization dynamics that provide a predictive framework for manipulating community composition through nutritional perturbations.

The gut-liver axis plays a crucial role in maintaining metabolic balance and overall human health. It orchestrates various processes, such as blood flow, nutrient transfer, metabolite processing, and immune cell communication between the two organs. Traditional methods, such as animal models and two-dimensional (2D) cell cultures, are insufficient in fully replicating the intricate functions of the gut-liver axis. The emergence of microfluidic technology has revolutionized this field, facilitating the development of organ-on-a-chip (OOC) systems. These systems are capable of mimicking the complex structures and dynamic environments of the gut and liver in vitro and incorporating sensors for real-time monitoring. In this article, we review the latest progress in gut-on-a-chip (GOC) and liver-on-a-chip (LOC) systems, as well as the integrated gut-liver-on-a-chip (GLOC) models. Our focus lies in the simulation of physiological parameters, three-dimensional (3D) structural mimicry, microbiome integration, and multicellular co-culture. All these aspects are essential for constructing accurate in vitro models of the gut and liver. Furthermore, we explore the current applications of OOC technology in the study of the gut and liver, including its use in disease modeling, toxicity testing, and drug screening. Finally, we discuss the challenges that remain and outline potential future directions for advancing GOC and LOC development in vitro.

Avian coccidiosis is an intestinal parasitic disease introduced by Eimeria spp., causing a major economic loss in the world poultry industry. Eimeria necatrix is the most pathogenic species that causes acute coccidiosis in chickens, leading to high mortality. Studies have shown that disruption of the gut environment due to Eimeria infection causes an imbalance in intestinal homeostasis. However, changes in the intestinal microbiota of chickens infected with E. necatrix remain unclear. In the present study, we performed full-length 16S ribosomal RNA amplicon sequencing to assess the effects of E. necatrix infection on jejunal and cecal microbiota at 4 and 10 days post-infection (dpi). The results showed that in both the infected and not infected groups at both time points, the most abundant phyla were Firmicutes, Proteobacteria and Bacteroidetes in the jejunum, and Firmicutes, Bacteroidetes and Proteobacteria in the cecum. The most common genera in the jejunum were Lactobacillus, Limosilactobacillus and Ligilactobacillus at 4 dpi, and Lactobacillus, Limosilactobacillus and Enterococcus in the infected group, and Lactobacillus, Limosilactobacillus and Streptococcus in the control group at 10 dpi. In the cecum, the most common genera were Phocaeicola, Lactobacillus and Alistipes at 4 dpi, and Lactobacillus, Phocaeicola and Alistipes in the infected group, and Lactobacillus, Phocaeicola and Bacteroides in the control group at 10 dpi. A total of 1528 species was annotated, and differences in relative abundance at the species level were analyzed using Lefse method. The results showed that the relative abundance of 23 species, including Acetilactobacillus jinshanensis, Anaerotruncus colihominis, Bacteroides heparinolyticus, Bacteroides ndongoniae, Bariatricus comes, Bifidobacterium gallinarum, Blautia coccoides, Butyricimonas paravirosa, Caproiciproducens galactitolivorans, Clostridioides difficile, Enterococcus cecorum, Escherichia coli, Intestinimonas timonensis, Lachnoanaerobaculum umeaense, Lactobacillus acetotolerans, Ligilactobacillus aviarius, Ligilactobacillus aviarius _B, Limosilactobacillus oris, Limosilactobacillus vaginalis, Megamonas funiformis, Plesiomonas shigelloides, Streptococcus pneumoniae, and Veillonella denticariosi, were significantly different between the infected and not infected groups. Our data reveal that E. necatrix infenction disrupts the integrity of gut microbiota, potentially promoting the establishment and growth of pathogenic bacteria; some species such as Bariatricus comes and Ligilactobacillus aviarius_B may be associated with the pathogenicity of the coccidian parasite and recovery of coccidiosis.

The gut microbiome functions as a metabolic organ, producing numerous enzymes that influence host health; however, their substrates and metabolites remain largely unknown.

We present MicrobeRX, an enzyme-based metabolite prediction tool that employs 5487 human reactions and 4030 unique microbial reactions from 6286 genome-scale models, as well as 3650 drug metabolic reactions from the DrugBank database (v.5.1.12). MicrobeRX includes additional analysis modules for metabolite visualization and enzymatic and taxonomic analyses. When we applied MicrobeRX to 1083 orally administered drugs that have been approved in at least one jurisdiction at some point in time (DrugBank), it predicted metabolites with physicochemical properties and structures similar to metabolites found in biosamples (from MiMeDB). It also outperformed another existing metabolite prediction tool (BioTransformer 3.0) in terms of predictive potential, molecular diversity, reduction of redundant predictions, and enzyme annotation.

Our analysis revealed both unique and overlapping metabolic capabilities in human and microbial metabolism and chemo- and taxa-specific microbial biotransformations. MicrobeRX bridges the genomic and chemical spaces of the gut microbiome, making it a valuable tool for unlocking the chemical potential of the gut microbiome in human health, the food and pharmaceutical industries, and environmental safety. Video Abstract.

Obesity, a pressing global health issue, is intricately associated with distinct gut microbiota profiles. Bariatric surgeries, such as Laparoscopic Sleeve Gastrectomy (LSG), Sleeve Gastrectomy (SG), and Roux-en-Y Gastric Bypass (RYGB), induce substantial weight loss and reshape gut microbiota composition and functionality, yet their comparative impacts remain underexplored.

This study integrated four published metagenomic datasets, encompassing 500 samples, and employed a unified bioinformatics workflow for analysis. We assessed gut microbiota α-diversity, identified species biomarkers using three differential analysis approaches, and constructed high-quality Metagenome-Assembled Genomes (MAGs). Comparative genomic, functional profiling and KEGG pathway analyses were performed, alongside estimation of microbial growth rates via Peak-to-Trough Ratios (PTRs).

RYGB exhibited the most pronounced enhancement of gut microbiota α-diversity compared to LSG and SG. Cross-cohort analysis identified 39 species biomarkers: 27 enriched in the non-obesity group (NonOB_Enrich) and 12 in the obesity group (OB_Enrich). Among the MAGs, 177 were NonOB_Enrich and 14 were OB_Enrich. NonOB_Enrich MAGs displayed enriched carbohydrate degradation profiles (e.g., GH105, GH2, GH23, GH43, and GT0 families) and higher gene diversity in fatty acid biosynthesis and secondary metabolite pathways, alongside significant enrichment in amino acid metabolism (KEGG analysis). Post-surgery, Akkermansia muciniphila and Bacteroides uniformis showed elevated growth rates based on PTRs.

These findings underscore RYGB's superior impact on gut microbiota diversity and highlight distinct microbial functional adaptations linked to weight loss, offering insights for targeted therapeutic strategies.

Gut microbiota plays an important role in gut health, and its dysbiosis is closely related to the pathogenesis of various intestinal diseases. The field of gut microbiota and intestinal diseases has not yet been systematically quantified through bibliometric methods. This study conducted bibliometric analysis to delineate the evolution of research on gut microbiota and intestinal diseases. Data were sourced from the Web of Science Core Collection database from 2009 to 2023 and were scientometrically analyzed using CiteSpace. We have found that the number of annual publications has been steadily increasing and showing an upward trend. China and the Chinese Academy of Sciences are the country and institution with the most contributions, respectively. Frontiers in Microbiology and Nutrients are the journals with the most publications, while Plos One and Nature are the journals with the most citations. The field has shifted from focusing on traditional descriptive analysis of gut microbiota composition to exploring the causal relationship between gut microbiota and intestinal diseases. The research hotspots and trends mainly include the correlation between specific intestinal diseases and gut microbiota diversity, the mechanism of gut microbiota involvement in intestinal diseases, the exploration of important gut microbiota related to intestinal diseases, and the relationship between gut microbiota and human gut health. This study provides a comprehensive knowledge map of gut microbiota and intestinal diseases, highlights key research areas, and outlines potential future directions.

According to traditional Chinese medicine (TCM) constitutional theory, individuals with phlegm-dampness constitution (PDC) are at increased risk for metabolic disorders. Previous studies have indicated that PDC individuals exhibit gene expression changes associated with metabolic disorders, even individuals with normal metabolic indices. However, the biological mechanisms underlying these changes remain unclear. The gut microbiota has recently emerged as a promising avenue for elucidating TCM principles. Here, we revealed that individuals with PDC have distinct gut microbiota and serum metabolite profiles. A decrease in phytosphingosine was associated with increased PDC scores and metabolic disorder severity. Subsequent experiments demonstrated that Flavonifractor plautii can biosynthesize phytosphingosine, which was also negatively correlated with the PDC score. Interestingly, both F. plautii and phytosphingosine levels decreased in PDC subjects with normal metabolic indices. Fecal transplantation from these individuals accelerated the development of metabolic disorders in mice. However, supplementation with F. plautii and phytosphingosine ameliorated metabolic disorders by increasing phytosphingosine levels in the gut‒hepatic axis. Mechanistic investigations confirmed that phytosphingosine can directly bind to hepatic peroxisome proliferator-activated receptor α (PPARα) and activate its nuclear transcription activity, thereby regulating downstream gene expression related to glucose‒lipid metabolism. Our research indicates that the decrease in F. plautii and its product, phytosphingosine, contributes to gene expression changes related to metabolic disorders in PDC individuals and increases their susceptibility to metabolic disorders. These findings suggest that diagnosing PDC may be beneficial for identifying at-risk populations among apparently healthy individuals, thereby advancing the broader field of metabolic disorder prevention and TCM integration.

This study investigates the effects of three dietary additives-microencapsulated sodium butyrate (MSB), glycerol monolaurate (GML), and tributyrin (TB)-on the growth performance, various physiological parameters, gene expression, intestinal morphology, and microflora in Acanthopagrus schlegelii (black sea bream). The experiment utilized a 43.5% soybean meal (SBM) inclusion diet with four isonitrogenous and isoenergetic formulations: a control diet, and diets supplemented with MSB (0.24%), GML (0.04%), or TB (0.22%). The growth trial spanned eight weeks, and triplicate tanks were randomly assigned to each diet, with each tank containing 30 fish, each having an initial weight of 1.55 ± 0.01 g. Key outcomes included measurements of weight gain, specific growth rate, digestive enzyme activity, serum immune markers, antioxidant status, and intestinal morphology and, gut microbiota. Additionally, gene expression and microbiota analysis were conducted on intestinal tissues to assess the impact of these additives on gut health and immune response. The findings revealed that all three additives enhanced growth performance and improved intestinal health and gut microbiota but GML exhibited the most pronounced effects on intestinal barrier function and immune modulation, gene expression, and microflora, followed by MSB and TB. This study provides a comprehensive comparison of MSB, GML, and TB as feed additives for black sea bream, offering insights into their potential for improving fish health and optimizing aquaculture feed formulations.

Obesity is a major global concern and is generally attributed to a combination of genetic and environmental factors. Several hypotheses have been proposed to explain the evolutionary origins of obesity epidemic, including thrifty and drifty genotypes, and changes in thermogenesis. Here, we put forward the hypothesis of metaflammation, which proposes that due to intense selection pressures exerted by environmental pathogens, specific genes that help develop a robust defense mechanism against infectious diseases have had evolutionary advantages and that this may contribute to obesity in modern times due to connections between the immune and energy storage systems. Indeed, incorporating the genetic variations of gut microbiota into the complex genetic framework of obesity makes it more polygenic than previously believed. Thus, uncovering the evolutionary origins of obesity requires a multifaceted approach that considers the complexity of human history, the unique genetic makeup of different populations, and the influence of gut microbiome on host genetics.

Recent studies in humans have shown that certain pesticides could affect the composition and functions of the gut microbiota, an essential modulator of vertebrate physiology, leading to potential dysbiosis. However, this relationship remains largely unknown in wild birds despite the implications of pesticides in the current decline of farmland species. The present study sought to fill this gap by providing data on the association between pesticide concentrations in blood and gut microbiota characteristics in relation to individual traits in a farmland raptor, the Montagu's harrier (Circus pygargus). Results showed that females with higher body condition and higher pesticide load exhibited greater gut bacterial richness and diversity, while the relationship was opposite in males with higher body condition. In terms of taxonomic composition, Proteobacteria emerged as the dominant phylum across all nestlings. Differences in the abundance of specific phyla and genera were observed according to pesticide load, with higher levels of Bacteroidota and Leifsonia, but lower levels of Bulkholderia, in nestlings with higher pesticide concentrations in their blood. This study highlights differences in microbiota and contamination by several pesticides according to the phenotypic characteristics of a wild raptor, and shows that farmland birds can represent relevant biosentinels for assessing the health/proper functioning of ecosystems (One Health approach).

The gut-brain axis (GBA) represents a complex, bidirectional communication network that connects the central nervous system (CNS) and the gastrointestinal system. Our study aimed to explore the correlation between the intestinal microbiota and demyelinating diseases from a bibliometric perspective, focusing on research since 2014.

A comprehensive search was carried out on the Web of Science Core Collection (WoSCC) to locate studies on the intestinal microbiota and demyelinating diseases, with a focus on publications from 1 January 2014 to 29 March 2024. We visualized and analyzed the data using VOSviewer, CiteSpace, and Charticulator.

We gathered 429 scholarly articles on the intestinal microbiota and demyelinating disorders published in the past 10 years. Research concerning the intestinal microbiota and demyelinating diseases has demonstrated a consistent increase in frequency over time. The USA has the highest number of publications, while Canada has the highest average number of citations, reaching as high as 3,429, which is greater than that of the USA. Moreover, the journal with the highest number of publications was Frontiers in Immunology, with 33 publications and 1,494 citations. The majority of the scholars focused on "multiple sclerosis" and "gut microbiota," which are the primary keywords in the field of the intestinal microbiota and demyelinating diseases.

This study conducted a comprehensive analysis of existing research investigating the correlation between the intestinal microbiota and demyelinating diseases. Using advanced bibliometric tools such as VOSviewer and CiteSpace, this study analyzed the intricate relationship between the intestinal microbiota and the pathogenesis of demyelinating conditions. In addition, the study used literature statistical analysis to identify research hotspots and future directions in the field.

The pathogens inactivation in wastewater sludges is vitally important for safely managing solid wastes and protecting public and environmental health especially in the emergency. Reports have shown the effectiveness of lime to kill virus pathogens in sludges, but mechanism of virus inactivation and related human diseases is unclear. This study evaluated representative limes of CaO/CaO2 on actual viral microorganism inactivation by viral metagenomic sequencing technology. As results, the CaO2 treatment enhanced the sludge hydrolysis and enveloped viral pathogens suppression via EPS structure destruction by oxidative radical generations; while CaO suppressed most of none-enveloped plant related viral pathogens. Most of the viromes of plant virus including Virgaviridae and Nodaviridae were inactivated by CaO, but the human virus-Feirsviridae and plant virus-Solemoviridae were occurred after lime stabilization compared to untreated sludge, with abundances of 1 %-37 % and 21 %-32 % in CaO-treated (CaO-T) and CaO2-treated (CaO2-T) samples, respectively. In addition, metatranscriptome analysis revealed distinct gene expression patterns between the CaO-T and CaO2-T sludges, in which lipopolysaccharide biosynthesis (LPS) and aminoacyl-tRNA synthetases (ARSs) in CaO-T, the formation of ribosome in CaO2-T were crucial to RNA virus regrowth in sludge. These findings suggested neither of CaO and CaO2 could completely suppress pathogens in sludge, and the effect of representative limes of CaO and CaO2 on the viral pathogen diversity, abundance, and metabolic function of the core microbiome on virus suppression and regrowth were ignored. Therefore, combined processes were recommended to provide possible alternatives for sludge safe management in pandemic emergencies.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide; however, current treatment options are inadequate, necessitating the exploration of new therapeutic strategies. The microbiota significantly influences the tumor microenvironment, suggesting that probiotics may serve as promising candidates for cancer treatment. We previously identified a novel probiotic, Lactobacillus plantarum MM89 (L. plantarum MM89), which was found to regulate the immune microenvironment. However, its specific role in CRC remained unclear. In this study, we employed an azoxymethane/dextran sodium sulfate-induced carcinogenesis mouse model to evaluate the therapeutic effects of L. plantarum MM89 in vivo. Transcriptome analysis was conducted to elucidate the mechanisms of action of L. plantarum MM89. Ferroptosis induction in tumor cells was assessed through cell viability assays and C11-BODIPY staining. Liquid chromatography/mass spectrometry was used to identify metabolites derived from L. plantarum MM89. MitoTracker and MitoTracker CMXRos staining and ATP content measurements were performed to assess mitochondrial damage. L. plantarum MM89 significantly inhibited tumor growth in vivo and alleviated intestinal inflammation at non-tumor foci. Transcriptome analysis and immunohistochemistry revealed that L. plantarum MM89 enhanced arachidonic acid metabolism. Small molecules present in the L. plantarum MM89 supernatant induced ferroptosis in cancer cells, as indicated by cell viability and C11-BODIPY assays. Furthermore, γ-linolenic acid (γ-LA) derived from L. plantarum MM89 was shown to induce ferroptosis via mitochondrial damage. In conclusion, γ-LA derived from L. plantarum MM89 triggers ferroptosis in tumor cells by inducing mitochondrial damage, highlighting its potential as a novel therapeutic agent for CRC treatment.

Due to the continued aging of the global population, cardiovascular diseases (CVDs) remain the main cause of death worldwide, with millions of fatalities from diseases, including stroke and coronary artery disease, reported annually. Thus, novel therapeutic approaches and targets are urgently required for diagnosing and treating CVDs. Recent studies emphasize the vital part of gut microbiota in both CVD prevention and management. Among these, Faecalibacterium prausnitzii (F. prausnitzii) has emerged as a promising probiotic capable of improving intestinal health. Although preliminary investigations demonstrate that F. prausnitzii positively enhances cardiovascular health, research specifically connecting this strain to CVD outcomes remains limited. Based on current research and assessment of possible clinical applications, this paper aimed to investigate the positive effects on cardiovascular health using F. prausnitzii and its metabolites. Targeting gut flora is expected to become a mainstay in CVD treatment as research develops.

It is commonly known that food nutrition is closely related to human health. The complex interactions between food nutrients and diseases, influenced by gut microbial metabolism, present challenges in systematizing and practically applying knowledge. To address this, we propose a method for extracting triples from a vast amount of literature, which is used to construct a comprehensive knowledge graph on nutrition and human health. Concurrently, we develop a query-based question answering system over our knowledge graph, proficiently addressing three types of questions. The results show that our proposed model outperforms other state-of-art methods, achieving a precision of 0.92, a recall of 0.81, and an F1 score of 0.86 in the nutrition and disease relation extraction task. Meanwhile, our question answering system achieves an accuracy of 0.68 and an F1 score of 0.61 on our benchmark dataset, showcasing competitiveness in practical scenarios. Furthermore, we design five independent experiments to assess the quality of the data structure in the knowledge graph, ensuring results characterized by high accuracy and interpretability. In conclusion, the construction of our knowledge graph shows significant promise in facilitating diet recommendations, enhancing patient care applications, and informing decision-making in clinical research.

Obesity is associated with metabolic and immune perturbations (ie, insulin resistance, increased inflammation, and oxidative stress), circadian rhythm dysregulation, and gut microbial changes that can promote colorectal tumorigenesis. Colorectal cancer (CRC) is the third most incident cancer in the United States. This narrative review examines the effects of intermittend fasting on factors influencing colon tumorigenesis, such as body weight, metabolic and immune markers, circadian rythm, and the gut microbiota in humans. Findings suggest that intermittent fasting regimens can lead to weight loss and shifts in metabolic markers, which could be preventive for CRC but effects on the gut microbiota composition and functions still remains elusive.

The gut microbiota (GM) can affect the immune system, which can lead to a variety of diseases, as confirmed by many studies. However, the exact mechanism by which GM affects kidney stone incidence through the immune system remains unclear. This study used a two-step, two-sample Mendelian randomization (MR) analysis by inverse variance weighting (IVW) method as well as Bayesian weighting (BWMR) to find out how the gut microbiota and inflammatory cytokines contribute to kidney stones, followed by a mediated MR analysis to exploreHow inflammatory cytokines are involved in the connection with the gut microbiota and kidney stones. MR analysis revealed that seven intestinal flora were protective against kidney stones, including family. Actinomycetaceae, family.Clostridiaceae1, genus.Clostridiumsensustricto1, genus. Hungatella, genus.LachnospiraceaeUCG001, genus.LachnospiraceaeUCG008 and order. Actinomycetales, while four intestinal flora, including genus. Haemophilus, genus. RuminococcaceaeUCG010, order.Rhodospirillales and phylum.Actinobacteria may increase the risk of kidney stones. In addition, it was confirmed that seven Inflammatory cytokines DNER, IL-18, IL-1α, SLAMF1, STAMPB, CST5 and FGF-5 in association with kidney stones. Notably, the mediating MR indicated the causal effect of phylum. Actinobacteria and order. Rhodospirillales gut group on kidney stones was mainly modulated by IL-18 levels, with mediating effects accounting for 15.8% and 12.8% of the total effect, respectively. The present study demonstrates this phylum. Actinobacteria and order. Rhodospirillales flora have an important role in reducing the risk of kidney stones and act mainly by modulating IL-18 levels.

Many food nutrients suffer from a series of limitations such as poor water solubility, low stability and inadequate bioavailability. These challenges can be effectively improved by food-based delivery systems (FDSs). FDSs are a series of functional carriers developed based on food-borne macromolecules. Natural polysaccharides are widely used in FDSs due to their good bioactivity, functional properties, and biocompatibility. The complex structural and physicochemical properties of polysaccharides have led to the extremely diverse development of FDSs based on polysaccharides. This review summarizes the application of natural polysaccharides from different sources in the development of different types of FDSs and their functional properties. It also emphasizes the feasibility and theoretical strategies to tailor satisfactory properties (shape, size, surface charge and targeting properties) of polysaccharides-based oral delivery systems (PODS) based on the diverse structural characteristics (e.g., solubility, ion type, molecular weight) and bioactivities of polysaccharides. PODS are designed to meet the diverse requirements in term of stability, toxicity, adhesion, cellular uptake, retention time and release behavior. This review also discusses the advantages of PODS in addressing nutrient deficiencies in gastrointestinal environment, with a focus on their role in nutritional interventions for inflammatory bowel disease. This review contributed to the development for novel PODS with specific demand.

Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic (ANT) application and affect gene expression. In this study, we analyzed the expression of 13 key pancreatic genes and blood physiology parameters after administering one maximum residue limit of herbicide glyphosate (GLY), two ANTs, and one anticoccidial drug (AD). A total of 260 Ross 308 broilers aged 1‍-‍40 d were divided into the following four groups of 65 birds each: control group, which was fed the main diet (MD), and three experimental groups, which were fed MD supplemented with GLY, GLY+ANTs (enrofloxacin and colistin methanesulfonate), and GLY+AD (ammonium maduramicin), respectively. The results showed that the addition of GLY, GLY+ANTs, and GLY+AD caused significant changes in the expression of several genes of physiological and economic importance. In particular, genes related to inflammation and apoptosis (interleukin 6 (IL6), prostaglandin-endoperoxide synthase 2 (PTGS2), and caspase 6 (CASP6)) were downregulated by up to 99.1%, and those related to antioxidant protection (catalase (CAT), superoxide dismutase 1 (SOD1) and peroxiredoxin 6 (PRDX6)) by up to 98.6%, compared to controls. There was also a significant decline in the values of immunological characteristics in the blood serum observed in the experimental groups, and certain changes in gene expression were concordant with changes in the functioning of the pancreas and blood. The changes revealed in gene expression and blood indices in response to GLY, ANTs, and AD provide insights into the possible mechanisms of action of these agents at the molecular level. Specifically, these changes may be indicative of physiological mechanisms to overcome the negative effects of GLY, GLY+ANTs, and GLY+AD in broilers.

Varied congenital heart disease (CHD) may induce gut microbiota dysbiosis due to intestinal hypoperfusion or/and hypoxemia. Microbiota dysbiosis has been found in preoperative infants and cardiopulmonary bypass (CPB) exacerbated it further. However, the trajectory of gut microbiota from pre- to early post-CPB and one-year later remains unexplored. We examined this trajectory in the two most common CHDs, i.e., left-to-right shunt (ventricular septal defect, VSD) vs. right-to-left shunt (tetralogy of Fallot, TOF).

We enrolled 13 infants with VSD and 11 with TOF, and collected fecal samples at pre- and early post-CPB. 10 and 12 age- and gender-matched healthy control infants were enrolled respectively. We also enrolled 13 and 9 gender- and CHD diagnosis- and operation-matched one-year post-CPB patients, and 8 age- and gender-matched healthy control children. 16S rRNA sequencing of fecal samples were performed.

Compared to the control groups, both VSD and TOF pre-CPB groups had significantly increased Enterobacteriaceae and Shigella, and decreased Bifidobacterium (Ps ≤ 0.049). No significant change in microbial community diversity was observed between pre- and early post-CPB periods (Ps≥0.227). Compared with early post-CPB, one-year post-CPB groups had significantly increased short-chain fatty acids-producing microbes (Ps ≤ 0.025), and their microbial communities were close to that of the control group (Ps≥0.102). There was no significant difference in microbial communities between VSD and TOF groups in any of 3 periods (Ps≥0.055).

In children with VSD or TOF, gut microbiota dysbiosis existed preoperatively and were not significantly altered by CPB. One-year post-CPB, microbiota significantly improved towards normal. Similar microbial communities were found between children with VSD and TOF throughout the perioperative and long-term postoperative periods.

Neonatal calves' diarrhea, which can be severe enough to cause death, has a significant impact on the global cattle industry. In this study, alfalfa polysaccharides and seaweed polysaccharides were found to significantly improve the diarrhea condition in neonatal calves. To explore the underlying mechanisms, further microbiomic and metabolomic analyses were conducted. This study investigated the impact of alfalfa polysaccharides and seaweed polysaccharides on growth performance, serum metabolites, gut microbiota, and metabolomics in neonatal Holstein calves. A total of 24 newborn calves were randomly assigned to three groups, with 8 calves per treatment group. The control (CON) group was fed a basal diet, the alfalfa polysaccharide (AP) group received a basal diet supplemented with alfalfa polysaccharides (4 g/calf/day), and the seaweed polysaccharide group (SP) received a basal diet supplemented with seaweed polysaccharides (4 g/calf/day). These polysaccharides were plant extracts. Compared to the CON group, the results indicated that SP significantly enhanced the body weight, height, chest circumference, and average daily gain of Holstein calves (p < 0.05), while also reducing the diarrhea rate and improving manure scoring (p < 0.05). Compared to the CON, AP also reduced the diarrhea rate (p < 0.05). In terms of serum biochemistry, supplementation with AP and SP increased serum alkaline phosphatase (ALP) and insulin-like growth factor 1 (IGF-1) levels compared to the CON group (p < 0.05). Both AP and SP elevated serum catalase (CAT) and Total Antioxidant Capacity (T-AOC) levels, indicating enhanced antioxidant status (p < 0.05). Regarding immune responses, supplementation with AP and SP significantly increased serum complement component 3 (C3) and immunoglobulin M (IgM) levels, while significantly reducing pro-inflammatory cytokines interleukin-18 (IL-18), tumor necrosis factor alpha (TNF-α), and interferon-gamma (IFN-γ) compared to the CON group (p < 0.05). Microbiota analysis revealed that AP modulated the abundance of Firmicutes, while SP influenced the abundance of Prevotella and Succiniclasticum. AP and SP differentially influenced intestinal metabolites compared to the CON group, leading to enrichment in pathways related to immunity, antibacterial, and anti-inflammatory functions. These pathways included the biosynthesis of alkaloids from ornithine, lysine, and nicotinic acid, glucocorticoid and mineralocorticoid receptor canothersis/antagonists, secondary metabolite biosynthesis, and alkaloid biosynthesis from histidine and purine, thus alleviating intestinal inflammation. Therefore, by supplementing with AP and SP, the diarrhea rate in calves was reduced, and the immune function of Holstein calves was enhanced, while simultaneously promoting a higher relative abundance of beneficial gut bacteria and suppressing the relative abundance of pathogenic bacteria. Additionally, gut pathways associated with immune response and inflammation were modulated by AP and SP. This study provided valuable insights and theoretical underpinnings for the use of AP and SP in preventing diarrhea in neonatal calves.

Ascites syndrome (AS) is a metabolic disease that seriously affects the growth and development of broiler chickens. Intestinal microbiota play a significant role in the growth of broiler chickens. Therefore, further research on the relationship between AS and intestinal microbiota will help to better understand the impact of AS on broiler growth. In this study, 0.2% sodium chloride was added to the drinking water, which induced AS in broiler chickens, and we detected the influence of AS on the growth performance and cecal microbiota of broiler chickens. The results showed that AS significantly reduced the cecal microbial diversity of broiler chickens and affected the cecal microbial composition at the phylum and genus levels (p = 0.05). Further, LEfSe analysis revealed that AS significantly increased the abundance of Bacteroidetes (p = 0.035) while simultaneously reducing the abundance of Actinobacteria (p = 0.031) in the cecum. Additionally, the differential metabolites associated with polycyclic aromatic hydrocarbon degradation were significantly diminished. The findings suggest that AS may further impact the growth rate of broiler chickens by altering cecal microorganisms.

Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.

Ongoing global climate change is affecting all aspects of life on Earth, including human health. The gut microbiota is an important determinant of health in humans and other organisms, but how climate change affects gut microbiota remains largely unexplored. In this Review, I discuss how the changing climate might affect gut microbiota by altering the quantity and quality of food, as well as environmental microbiomes, such as enteric pathogen pressure and host physiology. Climate change-induced variability in food supply, shifts in elemental and macromolecular composition of plant and animal food, the proliferation of enteric pathogens, and the direct effects of high temperatures on gut physiology might alter gut microbiota in undesirable ways, increasing the health burden of climate change. The importance of different pathways might depend on many geographical, economic, and ecological factors. Microbiomes of populations in low-income countries might be disproportionally affected through greater climate change effects and poor mitigation on diet, pathogen burden, and host physiology.

Our study focused on a mouse model of obesity induced by a high-fat diet (HFD). We administered Semaglutide intraperitoneally (Ozempic ®-0.05 mg/Kg-translational dose) every seven days for six weeks. HFD-fed mice had higher blood glucose, lipid profile, and insulin resistance. Moreover, mice fed HFD showed high gut levels of TLR4, NF-kB, TNF-α, IL-1β, and nitrotyrosine and low levels of occludin, indicating intestinal inflammation and permeability, culminating in higher serum levels of IL-1β and LPS. Treatment with semaglutide counteracted the dyslipidemia and insulin resistance, reducing gut and serum inflammatory markers. Structural changes in gut microbiome were determined by 16S rRNA sequencing. Semaglutide reduced the relative abundance of Firmicutes and augmented that of Bacteroidetes. Meanwhile, semaglutide dramatically changed the overall composition and promoted the growth of acetate-producing bacteria (Bacteroides acidifaciens and Blautia coccoides), increasing hypothalamic acetate levels. Semaglutide intervention increased the number of hypothalamic GLP-1R+ neurons that mediate endogenous action on feeding and energy. In addition, semaglutide treatment reversed the hypothalamic neuroinflammation HDF-induced decreasing TLR4/MyD88/NF-κB signaling and JNK and AMPK levels, improving the hypothalamic insulin resistance. Also, semaglutide modulated the intestinal microbiota, promoting the growth of acetate-producing bacteria, inducing high levels of hypothalamic acetate, and increasing GPR43+ /POMC+ neurons. In the ARC, acetate activated the GPR43 and its downstream PI3K-Akt pathway, which activates POMC neurons by repressing the FoxO-1. Thus, among the multifactorial effectors of hypothalamic energy homeostasis, possibly higher levels of acetate derived from the intestinal microbiota contribute to reducing food intake.

Xylooligosaccharides (XOS) ameliorate insulin resistance (IR) in gestational diabetes mellitus (GDM) probably by propagating Akkermansia muciniphila (Akk). This study aimed to investigate the effects and mechanisms of XOS, Akk and combination on IR in GDM mice/pseudo-germ-free (PGF) mice. Female mice were fed with AIN-93 (n = 19) and high fat diet (HFD) (n = 206). After 4 weeks, HFD-fed mice were further allotted to HFD, GDM, GDM + XOS, GDM + Akk, GDM + XOS + Akk, GDM + PGF, GDM + PGF + XOS, GDM + PGF + Akk, and GDM + PGF + XOS + Akk groups (n ≥ 19). GDM was induced by intraperitoneally injecting streptozotocin and PGF was established by intragastrically administrating antibiotic cocktails. XOS (500 mg/kg·BW) or/and Akk (4 × 108 CFU) were gavaged once a day for 10 days. Fasting blood glucose (FBG), insulin, oral glucose tolerance test (OGTT) and insulin signaling pathway were determined. Gut microbiota were detected by 16S rRNA sequencing and absolute quantities of Akk by qRT-PCR. Intestinal tissues were stained by Hematoxylin-Eosin and Periodic acid-Schiff-Alcian blue staining. Occludin and Zonula occludens-1 (ZO-1) in intestine, Natural killer group 2 member D (NKG2D) on intestinal epithelial lymphocytes (IELs) and NKG2D ligands (NKG2DL) on intestinal epithelial cells (IECs) were detected by Western blotting. In GDM mice, XOS, Akk and XOS + Akk reduced (p < 0.05) the area under the curve of OGTT (AUC), insulin and homeostasis model assessment of insulin resistance (HOMA-IR), and increased (p < 0.05) protein kinase B (Akt) phosphorylation in liver and insulin receptor substrate 1 (IRS-1) phosphorylation in muscle. Furthermore, XOS + Akk reduced (p < 0.05) FBG and increased (p < 0.05) Akt phosphorylation in muscle and IRS-1 phosphorylation in liver. XOS, Akk and XOS + Akk reshaped gut microbiota with XOS + Akk exhibiting the greatest effectiveness. XOS increased (p < 0.05) Akk and clearance of gut microbiota abolished such effect. XOS, Akk and XOS + Akk reduced (p < 0.05) the small intestine Chiu's score and the colon Dieleman's scores, increased (p < 0.05) ZO-1 and Occludin, and reduced (p < 0.05) NKG2D on IELs and NKG2DLs (H60, MULT-1, Rae-1ε) on IECs. Moreover, XOS + Akk reduced (p < 0.05) MULT-1 in duodenum. Collectively, XOS and Akk synergistically ameliorate IR by reshaping gut microbiota, improving intestinal barrier and regulating NKG2D/NKG2DL signaling in GDM mice.