Plant health and productivity are closely tied to the fluctuations of soil microbiomes, which regulate biogeochemical processes and plant-soil interactions. However, environmental and anthropogenic stressors, including climate change, intensive agricultural practices, and industrial activities, disrupt these microbial communities. This microbial imbalance reduces soil fertility, plant health, and biodiversity, threatening agroecosystem sustainability. This review explores the mechanisms driving microbial dysbiosis in soil and plant environments. Plants under stress release chemical signals through root exudates, dynamically recruiting beneficial microbes to counteract microbial imbalances. Moreover, this review evaluates traditional methods to alleviate these stress-induced microbial alterations, such as microbial inoculants and organic soil amendments, alongside innovative strategies like phage therapy, CRISPR, and small RNA-based technologies. Despite these advancements, the practical implementation of microbiome interventions faces significant challenges. These include regulatory hurdles, economic constraints, and the need for long-term field studies to validate efficacy and ensure environmental safety.

The COVID-19 pandemic has raised concerns about potential links between SARS-CoV-2 infection and autoimmune diseases. This study investigated changes in the incidence rate (IR) of autoimmune diseases among children following the pandemic's onset.

A retrospective cross-sectional study analyzed data from Clalit Health Services, Israel's largest healthcare provider, examining the IR of different autoimmune diseases in children aged 0-18. The study compared pre-pandemic (2019) with pandemic/post-pandemic periods (2020-2023), encompassing a cohort of over 1.5 million children.

Significant IR increases were observed across multiple autoimmune diseases. Rheumatic diseases (Juvenile Idiopathic Arthritis, Systemic Lupus Erythematosus, Henoch Schoenlein Purpura (HSP)) showed consistent increases, with HSP demonstrating the most pronounced trend. Endocrine disorders exhibited diverse patterns, with autoimmune thyroid diseases and Type 1 diabetes showing overall increases, while diabetic ketoacidosis exhibited an initial spike followed by a decline. Gastrointestinal diseases displayed heterogeneous patterns; Celiac disease and Ulcerative colitis showed general increases, Crohn's disease showed a downward trend, and autoimmune hepatitis exhibited an initial significant decrease followed by a significant increase. Dermatological conditions, including Psoriasis and Vitiligo, demonstrated consistent elevations throughout 2020-2023. Immune Thrombocytopenia Purpura showed initial decreases followed by significant increases in 2022-2023.

This comprehensive analysis reveals significant changes in pediatric autoimmune disease incidence following the COVID-19 pandemic, suggesting potential associations between SARS-CoV-2 infection and autoimmune dysregulation. The diverse patterns observed across different conditions highlight the complex interplay between viral infection and autoimmunity, emphasizing the need for continued surveillance and investigation of long-term immunological consequences of COVID-19 in pediatric populations.

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.

The community of microorganisms inhabiting a specific environment, such as the human gut - including bacteria, fungi, archaea, viruses, protozoa, and others - is known as the microbiota. A holobiont, in turn, refers to an integrated ecological unit where microbial communities function and interact with their host, thus is a more integrative concept. To understand the processes involved, the diversity of microorganisms present must be identified and their molecular components quantified, especially proteins. Indeed, proteins - through their roles as catalytic units, structural components, and signaling molecules - are the main drivers of biological processes. Metagenomics has significantly expanded what we know about the genetic material present in microbiota, revealing their functional potential; metabolomics delivers an overall snapshot of the metabolites produced by the community. But metaproteomics offers a complementary approach to explore microbiome and holobiont functionality by focusing on the active proteins and functional pathways from each taxon. Significant recent advances in high-resolution tandem mass spectrometry have greatly expanded the catalog of peptide sequences accessible in each sample, creating the conditions for unprecedented taxonomical profiling, while also providing more accurate biomass quantification, more detailed protein characterization, and a greater capacity to monitor abundance and distinguish host biomarkers. By integrating artificial intelligence into the metaproteomics pipeline, extended datasets can now be efficiently mined to gain a more comprehensive functional view of complex biological systems, paving the way for next-generation metaproteomics. In this perspective, I discuss the transformative potential of this methodology. We are on the cusp of a remarkable omic revolution that promises to uncover the intricate workings of microbiomes by producing a vast array of new knowledge with multiple applications. SIGNIFICANCE: Metaproteomics provides a powerful lens to investigate microbiome and holobiont functionality by identifying and quantifying active proteins and functional pathways within each taxon. Recent breakthroughs in high-resolution tandem mass spectrometry have dramatically expanded the repertoire of peptide sequences detectable per sample. This progress enables unprecedented taxonomic resolution for microbial identification, more precise biomass quantification, comprehensive protein characterization, abundance monitoring, and the unique identification of host biomarkers. In this commentary, I delve into the distinctive features that make metaproteomics a transformative tool. I discuss the recent advancements in tandem mass spectrometry and argue that the primary challenge in analyzing complex samples is shifting from data acquisition to data interpretation. With the integration of artificial intelligence, I believe next-generation metaproteomics is poised to become the next Big Thing in microbiome research, unlocking profound insights into microbial functionality and ecosystem dynamics.

Short-chain fatty acids (SCFAs), the primary metabolites produced by the microbial fermentation of dietary fibers in the gut, have a key role in protecting gut health. Increasing evidence indicates SCFAs can exert effects on distant tissues and organs beyond the gut via blood circulation. Osteoarthritis (OA) is a chronic inflammatory joint disease that severely diminishes the physical function and quality of life. However, effective clinical treatments for OA remain elusive. Recent studies have shown that SCFAs can exert beneficial effects on damaged joints in OA. SCFAs can mitigate OA progression by preserving intestinal barrier function and maintaining the integrity of cartilage and subchondral bone, suggesting that they have substantial potential to be the adjunctive treatment strategy for OA. This review described the SCFAs in the human body and their cellular signaling mechanism, and summarized the multiple effects of SCFAs (especially butyrate, propionate, and acetate) on the prevention and treatment of OA by regulating the gut-joint axis, providing novel insights into their promising clinical applications.

Anorexia nervosa (AN) is a complex and serious mental disorder, which may affect individuals of all ages and sex, but primarily affecting young women. The disease is characterized by a disturbed body image, restrictive eating behavior, and a lack of acknowledgment of low body weight. The underlying causes of AN remain largely unknown, and current treatment options are limited to psychotherapy and nutritional support. This paper investigates the impact of Fecal Microbiota Transplants (FMT) from patients with AN on food intake, body weight, behavior, and gut microbiota into antibiotic-treated mice. Two rounds of FMT were performed using AN and control (CO) donors. During the second round of FMT, a subset of mice received gut microbiota (GM) from a different donor type. This split-group cross-over design was chosen to demonstrate any recovery effect of FMT from a non-eating disorder state donor. The first FMT, from donors with AN, resulted in lower food intake in mice without affecting body weight. Analysis of GM showed significant differences between AN and CO mice after FMT1, before cross-over. Specific bacterial genera and families Ruminococcaceae, Lachnospiraceae, and Faecalibacterium showed different abundances in AN and CO receiving mice. Behavioral tests showed decreased locomotor activity in AN mice after FMT1. After FMT2, serum analysis revealed higher levels of appetite-influencing hormones (PYY and leptin) in mice receiving AN-GM. Overall, the results suggest that AN-GM may contribute to altered food intake and appetite regulation, which can be ameliorated with FMT from a non-eating disorder state donor potentially offering FMT as a supportive treatment for AN.

The gut microbiome influences physiological responses to exercise by modulating inflammatory markers and metabolite production. Athletes typically exhibit greater microbial diversity, which may be associated with improved performance, but the mechanisms linking different exercise modalities to the gut microbiome are not fully understood. In this study, blood and stool samples were collected from endurance athletes, strength athletes, and non-athletic controls performing two maximal exercise tests (the anaerobic Wingate test and the aerobic Bruce Treadmill Test) to integrate serum biomarker data with gut bacterial metagenomic profiles. While most biochemical markers showed similar post-exercise trends across groups, SPARC (secreted protein acidic and rich in cysteine) and adiponectin levels showed modality-specific responses. Strength-trained participants showed unique microbiome-biomarker associations after the Wingate test. In addition, baseline enrichment of certain bacterial taxa, including Clostridium phoceensis and Catenibacterium spp., correlated with reduced Bruce Treadmill test response in strength-trained individuals. These findings, while requiring further validation, indicate the complex interplay between exercise type, training background, and the gut microbiome, and suggest that specific microbial species may help shape recovery and adaptation.

Oxymatrine (OMT), a quinolizidine alkaloid derived from Sophora flavescens Ait., has demonstrated therapeutic potential in type 2 diabetes mellitus (T2DM). This study aimed to investigate its effects on diabetic osteoporosis (DOP) and explore the underlying mechanisms involving gut microbiota and osteogenic regulation.

In a rat model of T2DM, intragastric Oxymatrine was used to study trabecular bone repair through bone microstructure and histopathology analyses. Changes in gut microbiota, especially Gram-negative bacteria releasing lipopolysaccharides (LPS), were assessed via 16S rRNA sequencing. miRNA sequencing on LPS-induced rat osteoblasts, with and without Oxymatrine, explored osteoblast proliferation, mineralization, and the miR-539-5p/OGN/Runx2 pathway.

The administration of OMT resulted in an enhancement of diabetic osteopathy by reversing trabecular bone loss and modifying the composition of gut microbiota, specifically affecting Gram-negative bacteria that release LPS into the bloodstream. miRNA sequencing revealed that miR-539-5p, which was upregulated in LPS-induced ROBs, was downregulated following OMT treatment. Furthermore, OMT was found to promote osteoblast proliferation and mineralization under conditions of LPS exposure and modulate the miR-539-5p/OGN/Runx2 signaling pathway.

OMT improves diabetic osteoporosis by altering gut microbiota, decreasing LPS release, and enhancing osteoblast growth and differentiation through the miR-539-5p/OGN/Runx2 pathway, suggesting its potential as a treatment.

Spondyloarthritis (SpA) is a heterogenous group of diseases with an yet unknown exact pathogenesis. An interplay between genetic predispositionw (mainly HLA-B*27 positivity), a barrier leakage (of skin and gut) and environmental influences, such as the contact to certain microbiota are suspected to lead to an activation of the immune system and through this to the development and maintenance of the disease.

The gut microbiota plays crucial roles in the development and functions of the central nervous system (CNS) as well as in modulation of neurobehavior in heath and disease. The gut brush border enzyme intestinal alkaline phosphatase (IAP) is an important positive regulator of gut microbial homeostasis. In mice, IAP is encoded by Akp3 gene, which is specifically expressed in the duodenum of the small intestine. IAP deficiency alters gut bacterial composition and gut barrier function. Decreased IAP activity has been observed in aging, gut inflammatory diseases, and metabolic disorders. We hypothesized that this enzyme could also play an important role in modulating neurobehavior. We performed deep sequencing of gut bacterial 16S rRNA and found that IAP deficiency changed gut microbiota composition at various taxonomic levels. Using targeted metabolomic analysis, we also found that IAP deficiency resulted in changes of gut bacteria-derived metabolites in serum and brain metabolism. Neurobehavioral analyses revealed that Akp3-/- (IAP knockout) mice had decreased basal nociception thresholds, increased anxiety-like behavior, and reduced locomotor activity. Furthermore, Akp3-/- mice had more pronounced brain microglial phagocytic activity, together with an increase in the activated microglia population. Fecal microbiota transplantation from wildtype to Akp3-/- mice partially improved neurobehavior and reduced brain microglial phagocytic activity in Akp3-/- mice. This study demonstrates that deficiency of the endogenous gut-derived host factor IAP induces behavioral phenotype changes (nociception; motor activity, and anxiety) and affects brain microglia activity. Changes in the gut microbiota induced by knocking down Akp3 contribute to behavioral changes, which is probably mediated by microglia activity modulated by the gut bacteria-derived metabolites.

The prevalence of allergic diseases has been rising, paralleling lifestyle changes and environmental exposures that have altered human microbiome composition. This review article examines the intricate relationship between the gut microbiome and allergic diseases, emphasizing the potential of fecal microbiota transplantation as a promising novel treatment approach. It explains how reduced microbial exposure in modern societies contributes to immune dysregulation and the increasing incidence of allergies. The discussion also addresses immune homeostasis and its modulation by the gut microbiome, highlighting the shift from eubiosis to dysbiosis in allergic conditions. Furthermore, this article reviews existing studies and emerging research on the role of fecal microbiota transplantation in restoring microbial balance, providing insights into its mechanisms, efficacy, and safety.

Dysbiosis of gut microbiome is one of the most important factors leading to inflammatory bowel disease (IBD). Intake of phytochemicals from fruits and vegetables is an effective way to improve IBD, but how these bioactivators regulate gut microbiota to exert healthy effects remains unclear. Here, we found that pretreatment with CiLi juice, particularly its polyphenol component, alleviated dextran sulfate sodium (DSS)-induced colitis while preserving intestinal barrier integrity. CiLi polyphenols (CL_PP) reduced inflammation and oxidative stress in colon tissue and enriched fecal short-chain fatty acids. Importantly, CL_PP significantly regulated the gut microbiome diversity, increasing beneficial bacteria (e.g., Clostridia_UCG-014, f_Muribaculaceae and Ileibacterium_valens) while decreasing harmful bacteria (Escherichia-Shigella and Romboutsia). Multiomics analysis revealed that CL_PP upregulated bioactive lipid metabolites, particularly those derived from polyunsaturated fatty acids (e.g., resolvin D2, prostaglandin A1, and glycerophosphocholine) related gene expressions (Pltp, Alox15 and Pld4). Additionally, CL-PP downregulated the oxidative stress markers (oxidized glutathione and glutathione peroxidase 3), and immune cell markers (CD8 and CD68). Fecal microbiota transplantation confirmed that the fecal microbiota from CL_PP-treated mice exhibited anti-colitis effects. These effects were diminished in antibiotic-treated mice, underscoring the importance of the gut microbiota in mediating the CL_PP's anti-inflammatory benefits. This study suggests that CL_PP is a potential modulator of gut microbiome dysbiosis for the prevention and treatment of colitis.

A high-fat, low-fibre Western-style diet (WD) induces microbiome dysbiosis characterized by reduced taxonomic diversity and metabolic breadth1,2, which in turn increases risk for a wide array of metabolic3-5, immune6 and systemic pathologies. Recent work has established that WD can impair microbiome resilience to acute perturbations such as antibiotic treatment7,8, although little is known about the mechanism of impairment and the specific consequences for the host of prolonged post-antibiotic dysbiosis. Here we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) or WD, and find that only mice on RC undergo a rapid successional process of recovery. Metabolic modelling indicates that a RC diet promotes the development of syntrophic cross-feeding interactions, whereas in mice on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither. Furthermore, prolonged post-antibiotic dysbiosis in mice on WD renders them susceptible to infection by the intestinal pathogen Salmonella enterica serovar Typhimurium. Our data challenge widespread enthusiasm for faecal microbiota transplant (FMT) as a strategy to address dysbiosis, and demonstrate that specific dietary interventions are, at a minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural and less invasive alternative.

Alpha-synuclein aggregation, a hallmark of Parkinson's disease (PD), is hypothesized to often begin in the enteric or peripheral nervous system in "body-first" PD and progresses through the vagus nerve to the brain, therefore REM sleep behavior disorder (RBD) precedes the PD diagnosis. In contrast, "brain-first" PD begins in the central nervous system. Evidence that gut microbiome imbalances observed in PD and idiopathic RBD exhibit similar trends supports body-first and brain-first hypothesis and highlights the role of microbiota in PD pathogenesis. However, further investigation is needed to understand distinct microbiome changes in body-first versus brain-first PD over the disease progression.

Our investigation involved 104 patients with PD and 85 of their spouses as healthy controls (HC), with 57 patients (54.8%) categorized as PD-RBD(+) and 47 patients (45.2%) as PD-RBD(-) based on RBD presence before the PD diagnosis. We evaluated the microbiome differences between these groups over the disease progression through taxonomic and functional differential abundance analyses and carbohydrate-active enzyme (CAZyme) profiles based on metagenome-assembled genomes. The PD-RBD(+) gut microbiome showed a relatively stable microbiome composition irrespective of disease stage. In contrast, PD-RBD(-) microbiome exhibited a relatively dynamic microbiome change as the disease progressed. In early-stage PD-RBD(+), Escherichia and Akkermansia, associated with pathogenic biofilm formation and host mucin degradation, respectively, were enriched, which was supported by functional analysis. We discovered that genes of the UDP-GlcNAc synthesis/recycling pathway negatively correlated with biofilm formation; this finding was further validated in a separate cohort. Furthermore, fiber intake-associated taxa were decreased in early-stage PD-RBD(+) and the biased mucin-degrading capacity of CAZyme compared to fiber degradation.

We determined that the gut microbiome dynamics in patients with PD according to the disease progression depend on the presence of premotor RBD. Notably, early-stage PD-RBD(+) demonstrated distinct gut microbial characteristics, potentially contributing to exacerbation of PD pathophysiology. This outcome may contribute to the development of new therapeutic strategies targeting the gut microbiome in PD. Video Abstract.

Gut microbiota play a critical role in mediating the bidirectional association between cancer and depression. Emerging evidence indicates that adjusting the dietary component intake can significantly alter gut microbiota composition, thereby influencing the host's metabolism and immune function. Changes in gut microbiota and their metabolites may represent key factors in preventing cancer-depression comorbidity.

English publications were searched in databases including the Web of Science, Scopus, and PubMed using a series of keywords: "cancer", "depression", "gut microbiota", "dietary components", and related terms, individually or in combination. The search focused on preclinical and clinical studies describing the regulatory effects of dietary component interventions.

This narrative review summarizes the associations among gut microbiota, cancer, and depression, and synthesizes current evidence on the modulatory effects and mechanisms of specific dietary component interventions, including dietary patterns, probiotics, prebiotics, and diet-derived phytochemicals, on gut microbiota. On the one hand, these interventions inhibit abnormal proliferation signals in the tumor microenvironment and enhance anticancer immune responses; on the other hand, they modulate neurotransmitter homeostasis, suppress neuroinflammation, and improve mood behaviors through the gut-brain axis interactions mediated by microbial metabolites.

The complex associations among cancer, depression, and gut microbiota require further clarification. Modulating gut microbiota composition through dietary components represents a novel therapeutic strategy for improving cancer-depression comorbidity. Regulated gut microbiota enhance immune homeostasis and intestinal barrier function, while their metabolites bidirectionally modulate one another via systemic circulation and the gut-brain axis, thereby improving both the tumor microenvironment and depressive-like behaviors in cancer patients while reducing the adverse effects of cancer.

Ziziphi Spinosae Semen saponins (ZSSS) show sedative-hypnotic activity but have very low bioavailability, potentially due to their conversion into bioactive metabolites by gut microbiota. In this study, the biotransformation of ZSSS by gut microbiota from healthy humans and patients with insomnia in vitro was analyzed. A total of 21 prototype compounds and 49 metabolites were identified using UHPLC-Q-Orbitrap-MS. Deglycosylation, deoxygenation, dehydration, and deacylation were detected in both healthy individuals and insomniacs. However, oxidation and hydrogenation were uniquely observed in insomniacs. ZSSS can enhance beneficial bacteria, such as Veillonella, Dialister, and Bacteroides. ZSSS can promote the synthesis of short-chain fatty acids (SCFAs), especially acetic acid, propionic acid, and butyric acid. Furthermore, it was found that the sedative-hypnotic activity of ZSSS was enhanced after biotransformation, as determined by a sodium pentobarbital-induced sleeping test (SPST), open-field behavior test (OFBT), and molecular docking experiment (MDE). These results collectively offer valuable insight into the mechanism of action of ZSSS.

Antibiotic treatment contributes to gut microbiota dysbiosis. Previous studies have shown that fecal microbiota transplantation (FMT), fecal filtrate (FF), and activated charcoal (AC) treatments can prevent gut microbiota disturbances caused by antibiotics or Clostridioides difficile infection. However, these treatments have typically been limited to restoring gut microbiota after dysbiosis, and antibiotics must be discontinued beforehand. Here, we investigated the protective effects of these treatments on gut microbiota to prevent dysbiosis during concurrent systemic ceftriaxone administration.

C57BL/6 mice that received intraperitoneal ceftriaxone for seven consecutive days were concomitantly treated with AC, FMT, FMT + AC, FF, or FF + AC via oral gavage. Gut microbiomes were analyzed using 16 S rRNA gene sequencing, and intestinal mucosal pathology was evaluated through H&E staining.

Systemic ceftriaxone administration significantly altered gut microbiota diversity and composition but did not affect intestinal mucosal histology. Alpha and beta diversity analyses showed that microbiota diversity decreased in all ceftriaxone-treated groups, with the ceftriaxone + FF + AC group retaining the highest diversity. The ceftriaxone + AC group had higher Enterococcus but lower Muribaculaceae relative abundances than the control (no ceftriaxone), ceftriaxone only, and ceftriaxone + FF + AC groups.

These results show that fecal filtrate transplantation combined with activated charcoal treatment may help balance gut microbiota diversity and reduce the presence of resistant bacteria during ceftriaxone exposure.

The gut microbiome, a complex community of microorganisms residing in the intestinal tract, plays a dual role in colorectal cancer (CRC) development, acting both as a contributing risk factor and as a protective element. This review explores the mechanisms by which gut microbiota contribute to CRC, emphasizing inflammation, oxidative stress, immune evasion, and the production of genotoxins and microbial metabolites. Fusobacterium nucleatum, Escherichia coli (pks+), and Bacteroides fragilis promote tumorigenesis by inducing chronic inflammation, generating reactive oxygen species, and producing virulence factors that damage host DNA. These microorganisms can also evade the antitumor immune response by suppressing cytotoxic T cell activity and increasing regulatory T cell populations. Additionally, microbial-derived metabolites such as secondary bile acids and trimethylamine-N-oxide (TMAO) have been linked to carcinogenic processes. Conversely, protective microbiota, including Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii, contribute to intestinal homeostasis by producing short-chain fatty acids (SCFAs) like butyrate, which exhibit anti-inflammatory and anti-carcinogenic properties. These beneficial microbes enhance gut barrier integrity, modulate immune responses, and inhibit tumor cell proliferation. Understanding the dynamic interplay between pathogenic and protective microbiota is essential for developing microbiome-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, to prevent or treat CRC. Future research should focus on identifying microbial biomarkers for early CRC detection and exploring personalized microbiome-targeted therapies. A deeper understanding of host-microbiota interactions may lead to innovative strategies for CRC management and improved patient outcomes.

Tuberculosis, primarily caused by Mycobacterium tuberculosis, is an airborne lung disease and continues to pose a significant global health threat, resulting in millions of deaths annually. The current treatment for tuberculosis involves a prolonged regimen of antibiotics, which leads to complications such as recurrence, drug resistance, reinfection, and a range of side effects. This scenario underscores the urgent need for novel therapeutic strategies to combat this lethal pathogen. Over the last two decades, microbiome therapeutics have emerged as promising next-generation drug candidates, offering advantages over traditional medications. In 2022, the Food and Drug Administration approved the first microbiome therapeutic for recurrent Clostridium infections, and extensive research is underway on microbiome treatments for various challenging diseases, including metabolic disorders and cancer. Research on microbiomes concerning tuberculosis commenced roughly a decade ago, and the scope of this research has broadened considerably over the last five years, with microbiome therapeutics now viewed as viable options for managing drug-resistant tuberculosis. Nevertheless, the understanding of their mechanisms is still in its infancy. Although autophagy has been extensively studied in other diseases, research into its role in tuberculosis is just beginning, with preliminary developments in progress. Against this backdrop, this comprehensive review begins by succinctly outlining tuberculosis' characteristics and assessing existing treatments' strengths and weaknesses, followed by a detailed examination of microbiome-based therapeutic approaches for drug-resistant tuberculosis. Additionally, this review focuses on establishing a basic understanding of microbiome treatments for tuberculosis, mainly through the lens of autophagy as a mechanism of action. Ultimately, this review aims to contribute to the foundational comprehension of microbiome-based therapies for tuberculosis, thereby setting the stage for the further advancement of microbiome therapeutics for drug-resistant tuberculosis.

Chrononutrition and diet quality appear to influence stress, however, evidence on this relationship needs to be better elucidated. We aim to assess the association between chrononutrition, diet quality, and perceived stress in adults from Southern Brazil. Population-based cross-sectional study conducted in two Brazilian cities, with individuals aged ≥18 years. Chrononutrition and diet quality were the exposure, and perceived stress was the outcome. To assess the associations, Poisson regression was used to calculate crude and adjusted prevalence ratio. 2,170 individuals were analyzed: 12.3% did not have breakfast, 27.5% had less than four meals per day, 30.4% presented poor diet quality, 14% referred irregular consumption of healthy foods, and 43.2% had regular consumption of unhealthy foods. Perceived stress was reported by 38.2% of the sample. Individuals who ate less than four meals per day, with poor diet quality, with regular consumption of unhealthy foods, and with irregular consumption of healthy foods were more likely to present perceived stress. These results may contribute to the development of joint actions on nutrition and mental health.

The microbiota is integral to human health and has been mostly characterized through various ex vivo 'omic'-based approaches. To better understand the real-time function and impact of the microbiota, in vivo molecular imaging is required. With technologies such as positron emission tomography (PET), magnetic resonance imaging (MRI), and computed tomography (CT), insight into microbiological processes may be coupled to in vivo information. Noninvasive imaging enables longitudinal tracking of microbes and their components in real time; mapping of microbiota biodistribution, persistence and migration; and simultaneous monitoring of host physiological responses. The development of molecular imaging for clinical translation is an interdisciplinary science, with broad implications for deeper understanding of host-microbe interactions and the role(s) of the microbiome in health and disease.

Antigen-specific recognition of microbiota by T cells enforces tolerance at homeostasis. Conversely, dysbiosis leads to imbalanced T-cell responses, triggering inflammatory and autoimmune diseases. Despite their significance, the identities of immunogenic microbial antigens remain largely enigmatic. Here, we leveraged a sensitive, unbiased, genome-wide screening platform to identify peptides from Akkermansia muciniphila (AKK) and Bacteroides thetaiotaomicron (BT) recognized by CD4+ T cells. The platform is based on screening peptide libraries using an NFAT-fluorescence reporter cell line transduced with a retrovirus encoding an MHC-TCR (MCR) hybrid molecule. We discovered several novel epitopes from AKK and BT. T-cell hybridomas reactive to AKK and BT bacteria demonstrated polyreactivity to microbiota-derived peptides in co-cultures with MCR reporter cells. Steady-state T cells recognized these epitopes in an MHC-restricted fashion. Intriguingly, most of the identified epitopes are broadly conserved within the given phylum and originate from membrane and intracellular proteins. Ex vivo stimulation of CD4+ T cells from mice vaccinated with the identified peptides revealed mono-specific IFN-γ and IL-17 responses. Our work showcases the potential of the MCR system for identifying immunogenic microbial epitopes, providing a valuable resource. Our study facilitates decoding antigen specificity in immune system-bacterial interactions, with applications in understanding microbiome and pathogenic bacterial immunity.

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.

This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition wherein excessive fat accumulates in the liver, leading to inflammation and potential liver damage. In this narrative review, we evaluate the tissue microbiota, how they arise and their constituent microbes, and the role of the intestinal and hepatic microbiota in MASLD. The history of bacteriophages (phages) and their occurrence in the microbiota, their part in the potential causation of MASLD, and conversely, "phage therapy" for antibiotic resistance, obesity, and MASLD, are all described. The microbiota metabolism of bile acids and dietary tryptophan and histidine is defined, together with the impacts of their individual metabolites on MASLD pathogenesis. Both periodontitis and intestinal microbiota dysbiosis may cause MASLD, and how individual microorganisms and their metabolites are involved in these processes is discussed. Novel treatment opportunities for MASLD involving the microbiota exist and include fecal microbiota transplantation, probiotics, prebiotics, synbiotics, tryptophan dietary supplements, intermittent fasting, and phages or their holins and endolysins. Although FDA is yet to approve phage therapy in clinical use, there are multiple FDA-approved clinical trials, and this may represent a new horizon for the future treatment of MASLD.

Oral cancer (OC) ranks among the most prevalent head and neck cancers, becoming the eleventh most common cancer worldwide with ~350,000 new cases and 177,000 fatalities annually. The rising trend in the occurrence of OC among young individuals and women who do not have tobacco habits is escalating rapidly. Surgical procedures, radiation therapy, and chemotherapy are among the most prevalent treatment options for oral cancer. To achieve better therapy and an early detection of the cancer, it is essential to understand the disease's etiology at the molecular level. Saliva, the most prevalent body fluid obtained non-invasively, holds a collection of distinct non-coding RNA pools (ncRNAomes) that can be assessed as biomarkers for identifying oral cancer. Non-coding signatures, which are transcripts lacking a protein-coding function, have been identified as significant in the progression of various cancers, including oral cancer. This review aims to examine the role of various salivary ncRNAs (microRNA, circular RNA, and lncRNA) associated with disease progression and to explore their functions as potential biomarkers for early disease identification to ensure better survival outcomes for oral cancer patients.

Coenzyme Q10 (CoQ10), an important fat-soluble, bioactive molecule that predominantly found in the inner mitochondrial membrane, is widely used in functional food and health food raw materials, which has garnered considerable attention due to its potential role in immunoregulation. However, the intrinsic mechanism of CoQ10 on immunity, and the relationship to the gut microbiota have not been elucidated.

Here, we conducted a series of in vivo experiments with the aim of comprehensively exploring the effect of CoQ10 on both cellular and humoral immune functions, and on gut microbiota communities in mice.

CoQ10 showed negligible impact on both mouse body weight fluctuations and tissue indices, but enhanced the mouse body immunity by elevating the carbon clearance ability and natural killer (NK) cellular viability. 16S rRNA gene sequencing revealed that administration of CoQ10 modulated the structure and composition of the gut microbiota in mice, notably by enhancing the abundance of Lactobacillus, Limosilactobacillus, and decreasing the abundance of Paramuribaculum species.

This work makes a contribution to the application of CoQ10 as an immunomodulator in the biological, pharmaceutical and health care product industries.

Chronic prostatitis/Chronic pelvis pain syndrome (CP/CPPS), a kind of frequent urinary condition among adult males, has caused a lot of inconvenience to patients in life, whose pathogenesis is unclear. Current evidence suggests that it is most likely to be an autoimmune disease. Symbiotic microbes, a highly diverse biological community that harbors trillions of microbes in each region of the human body, have gradually made people realize their important role in immune regulation, material metabolism, and health maintenance. In recent years, increasing studies have shown a connection between microbiota and CP/CPPS. In view of this, we performed this review to summarize the literature pertaining to microbiota and its association with the pathophysiological mechanism of CP/CPPS. In addition, we gleaned the latest progress in the therapeutic strategy of CP/CPPS that related to microbiota regulation in order to offer new perspectives on the management of CP/CPPS.

Perturbations in the intestinal microbiome are strongly linked to the pathogenesis of inflammatory bowel disease (IBD). Bacteria, fungi and viruses all make up part of a complex multi-kingdom community colonizing the gastrointestinal tract, often referred to as the gut microbiome. They can exert various effects on the host that can contribute to an inflammatory state. Advances in screening, multiomics and experimental approaches have revealed insights into host-microbiota interactions in IBD and have identified numerous mechanisms through which the microbiota and its metabolites can exert a major influence on the gastrointestinal tract. Looking into the future, the microbiome and microbiota-associated processes will be likely to provide unparalleled opportunities for novel diagnostic, therapeutic and diet-inspired solutions for the management of IBD through harnessing rationally designed microbial communities, powerful bacterial and fungal metabolites, individually or in combination, to foster intestinal health. In this Review, we examine the current understanding of the cross-kingdom gut microbiome in IBD, focusing on bacterial and fungal components and metabolites. We examine therapeutic and diagnostic opportunities, the microbial metabolism, immunity, neuroimmunology and microbiome-inspired interventions to link mechanisms of disease and identify novel research and therapeutic opportunities for IBD.

Sepsis is defined as a life-threatening condition caused by a dysregulated host response to infection, leading to multi-organ dysfunction, and representing a significant global health burden. The progression of sepsis is closely linked to disruptions in lung microbiota, including bacterial translocation, impaired barrier function, and local microenvironmental disturbances. Conversely, the worsening of sepsis exacerbates lung microbiota imbalances, contributing to multi-organ dysfunction. Recent culture-independent microbiological techniques have unveiled the complexity of the respiratory tract microbiome, necessitating a reassessment of the interactions between the host, microbes, and pathogenesis in sepsis. This review synthesizes current insights into the causes of microbiota dysbiosis and the regulatory mechanisms of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, as well as their interactions during sepsis and sepsis-induced organ dysfunction. In addition, we summarize novel diagnostic and therapeutic approaches from the current study that may offer promising prospects for the management of sepsis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex etiology. It has been suggested that the pathogenesis of RA begins in the mucosa and then transitions to the joints when many factors interact, including microbial dysbiosis, inflammatory responses, and immune abnormalities at the mucosal site. Data from RA animals and patients suggest there are changes in the mucosal microflora before the onset of RA, and that dysbiosis of the mucosal ecology continues to play a role in the development of arthritis. Microbial dysbiosis of the mucosa reduces the normal barrier function of the intestinal tract, promotes inflammatory reactions in the mucosal areas of the intestines, and then activates the intestinal immune cells abnormally to produce a large number of auto-reactive antibodies that exacerbate arthritis. Current findings do not clarify whether dysbiosis is only a potential trigger for the development of RA. If it is possible to intervene in such microbial changes before the onset of RA, could the clinical symptoms of arthritis be prevented or reduced? Finding new ways to regulate gut flora composition to maintain gut barrier function is an ongoing challenge for the prevention and treatment of RA.

Up to 25-35% of women receive antibiotics (ABX) during pregnancy, but little is known about the consequences on a key mucosal interface such as the mammary gland, and on the development of the neonatal gut's microbiota and IgA. We hypothesize that prenatal ABX negatively affect the immune functionality of mammary gland, the composition of breast milk microbiota, the development of neonatal fecal microbiota and the abundance of neonatal fecal IgA.

Case-control translational cohort study on women and neonates in the presence or absence (N = 41 + 41 pairs) of exposure to prenatal ABX for at least 7 consecutive days after 32 weeks of gestation.

We will evaluate IgA concentration in breast milk and in neonatal feces up to one year after delivery. We will also evaluate clinical parameters, neurodevelopment and the composition of the IgA-coated and uncoated fractions of breast milk and fecal microbiota by means of magnetic-activated cell sorting (MACS) coupled with shotgun metagenomics. Finally, we will measure the concentration of the chemokine CCL28 on maternal serum and breast milk, as a marker of activity of the entero-mammary pathway.

Our results might support a data-driven evaluation of breast milk immune function in women exposed to prenatal ABX.

Breast milk IgA and microbiota are critical to determine the positive effects of breastfeeding in infants. This research protocol will investigate breast milk IgA, microbiota, and the IgA+ / IgA- fractions of neonatal fecal microbiota upon exposure to prenatal antibiotics. Fecal IgA and microbiota in infants exposed or not exposed to prenatal antibiotics will be analyzed up to 1 year after birth. This research will clarify the impact of prenatal antibiotics on the immune function of breast milk. This, in turn, might support the selective evaluation of breast milk IgA/microbiota in mothers exposed to prenatal antibiotics, or in donor human milk.

Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder associated with oxidative stress (OS) and dysbiosis. Chaihushugan powder (CHSGP) demonstrates efficacy in treating FD; however, the underlying therapeutic mechanism is not yet elucidated. This study aims to investigate the effects of CHSGP on OS and gut microbiota (GM) in FD rats, with a particular emphasis on the role of GM as a potential target for the antioxidant properties of CHSGP.

The FD rat model was established with a modified tail-clamp stimulation and the administration of the CHSGP decoction at a dosage of 9.6 g/kg via gavage for a duration of 4 weeks. The GM was depleted by the administration of a cocktail of metronidazole (200 mg/kg), ampicillin (200 mg/kg), neomycin sulfate (200 mg/kg), and vancomycin (100 mg/kg). Fecal microbiota transplantation (FMT) was performed with CHSGP-treated fecal supernatant at a dosage of 10 mL/kg. The gastrointestinal motility was measured using the rates of gastric emptying and small intestine propulsion. Hematoxylin and eosin staining was employed to elucidate the pathological changes, while the transmission electron microscope was used to examine the microstructures of the interstitial cells of Cajal (ICC). Chemiluminescence, colorimetric assay, immunofluorescence co-staining, and western blot assay were employed to identify the OS-related markers (ROS, SOD, NOX4, PRDX1, and TRX2). Sequencing of fecal microbiota was performed utilizing 16S rDNA.

The CHSGP decoction promoted gastrointestinal motility, protected the microstructure of ICC, and reduced OS in FD rats. The GM composition was also regulated by CHSGP. However, these effects disappeared after microbiota depletion. Fortunately, the FMT therapy reinstated them.

Chaihushugan powder decoction might regulate the GM to alleviate mitochondrial OS in the gastric tissues of FD rats.

The role of gut microbiota (GM) and intestinal dysbiosis in triggering the onset and/or modulating the severity and progression of lupus nephritis (LN) has been the object of intense research over the last few years. Some alterations at the phyla level, such as the abundance of Proteobacteria and reduction in Firmicutes/Bacteroidetes (F/B) ratio and in α-diversity have been consistently reported in systemic lupus erythematosus (SLE), whereas a more specific role has been ascribed to some species (Bacteroides thetaiotaomicron and Ruminococcus gnavus) in LN. Underlying mechanisms include microbial translocation through a "leaky gut" and subsequent molecular mimicry, immune dysregulation (alteration of IFNγ levels and of balance between Treg and Th17 subsets), and epigenetic interactions. Levels of bacterial metabolites, such as butyrate and other short-chain fatty acids (SCFAs), appear to play a key role in modulating LN. Beyond bacterial components of GM, virome and mycobiome are also increasingly recognized as important players in the modulation of an immune response. On the other hand, microbiota-based therapy appears promising and includes diet, prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). The modulation of microbiota could correct critical alterations, such as F/B ratio and Treg/Th17 imbalance, and blunt production of autoantibodies and renal damage. Despite current limits, GM is emerging as a powerful environmental factor that could be harnessed to interfere with key mechanisms leading to SLE, preventing flares and organ damage, including LN. The aim of this review is to provide a state-of-the-art analysis of the role of GM in triggering and modulating SLE and LN on the one hand, while exploring possible therapeutic manipulation of GM to control the disease on the other hand.

Most brain development occurs in the "first 1000 days", a critical period from conception to a child's second birthday. Critical brain processes that occur during this time include synaptogenesis, myelination, neural pruning, and the formation of functioning neuronal circuits. Perturbations during the first 1000 days likely contribute to later-life neurodegenerative disease, including sporadic amyotrophic lateral sclerosis (ALS). Neurodevelopment is determined by many events, including the maturation and colonization of the infant microbiome and its metabolites, specifically neurotransmitters, immune modulators, vitamins, and short-chain fatty acids. Successful microbiome maturation and gut-brain axis function depend on maternal factors (stress and exposure to toxins during pregnancy), mode of delivery, quality of the postnatal environment, diet after weaning from breast milk, and nutritional deficiencies. While the neonatal microbiome is highly plastic, it remains prone to dysbiosis which, once established, may persist into adulthood, thereby inducing the development of chronic inflammation and abnormal excitatory/inhibitory balance, resulting in neural excitation. Both are recognized as key pathophysiological processes in the development of ALS.

Maximizing microbial functions for improving crop performance requires better understanding of the important drivers of plant-associated microbiomes. However, it remains unclear the forces that shapes microbial structure and assembly, and how plant seed-microbiome interactions impact grain quality. In this work, we characterized the seed endophytic microbial communities of malting barley from different geographical locations and investigated associations between microbial (bacterial and fungal) species diversity and malt quality traits. Host genotype, location, and interactions (genotype x location) significantly impacted the seed endophytic microbial communities. Taxonomic composition analysis identified the most abundant genera for bacterial and fungal communities to be Bacillus (belonging to phylum Firmicutes) and Blumeria (belonging to phylum Ascomycota), respectively. We observed that a greater proportion of bacterial amplicon sequence variants (bacterial ASVs) were shared across genotypes and across locations while the greater proportion of the fungal ASVs were unique to each genotype and location. Association analysis showed a significant negative correlation between bacterial alpha diversity indices (Faith PD and Shannon indices) and malt quality traits for barley protein (BP), free amino nitrogen (FAN), diastatic power (DP) and alpha amylase (AA), while fungal alpha diversity (Shannon and Simpson) showed significant negative relationship with β-D-glucan content. In addition, some bacterial and fungal genera were significantly associated with malt extract (ME) -a key trait for maltsters and brewers. We conclude that barley genotype, location, and their interactions shape the seed endophytic microbiome and is key to microbiome manipulation and management during barley production and/or malting.

Cellular aging is a multifactorial and intricately regulated physiological process with profound implications. The interaction between cellular senescence and cancer is complex and multifaceted, senescence can both promote and inhibit tumor progression through various mechanisms. M6A methylation modification regulates the aging process of cells and tissues by modulating senescence-related genes. In this review, we comprehensively discuss the characteristics of cellular senescence, the signaling pathways regulating senescence, the biomarkers of senescence, and the mechanisms of anti-senescence drugs. Notably, this review also delves into the complex interactions between senescence and cancer, emphasizing the dual role of the senescent microenvironment in tumor initiation, progression, and treatment. Finally, we thoroughly explore the function and mechanism of m6A methylation modification in cellular senescence, revealing its critical role in regulating gene expression and maintaining cellular homeostasis. In conclusion, this review provides a comprehensive perspective on the molecular mechanisms and biological significance of cellular senescence and offers new insights for the development of anti-senescence strategies.

Global warming augments the risk of adverse pregnancy outcomes in vulnerable expectant mothers. Pioneering investigations into heat stress (HS) have predominantly centered on its direct impact on reproductive functions, while the potential roles of gut microbiota, despite its significant influence on distant tissues, remain largely unexplored. Our understanding of deleterious mechanisms of HS and the development of effective intervention strategies to mitigate the detrimental impacts are still limited.

In this study, we aimed to explore the mechanisms by which melatonin targets gut microbes to alleviate HS-induced reproductive impairment.

We firstly evaluated the alleviating effects of melatonin supplementation on HS-induced reproductive disorder in pregnant mice. Microbial elimination and fecal microbiota transplantation (FMT) experiments were then conducted to confirm the efficacy of melatonin through regulating gut microbiota. Finally, a lipopolysaccharide (LPS)-challenged experiment was performed to verify the mechanism by which melatonin alleviates HS-induced reproductive impairment.

Melatonin supplementation reinstated gut microbiota in heat stressed pregnant mice, reducing LPS-producing bacteria (Aliivibrio) and increasing beneficial butyrate-producing microflora (Butyricimonas). This restoration corresponded to decreased LPS along the maternal gut-placenta-fetus axis, accompanied by enhanced intestinal and placental barrier integrity, safeguarding fetuses from oxidative stress and inflammation, and ultimately improving fetal weight. Further pseudo-sterile and fecal microbiota transplantation trials confirmed that the protective effect of melatonin on fetal intrauterine growth under HS was partially dependent on gut microbiota. In LPS-challenged pregnant mice, melatonin administration mitigated placental barrier injury and abnormal angiogenesis via the inactivation of the TLR4/MAPK/VEGF signaling pathway, ultimately leading to enhanced nutrient transportation in the placenta and thereby improving the fetal weight.

Melatonin alleviates HS-induced low fetal weight during pregnancy via the gut-placenta-fetus axis, the first time highlighting the gut microbiota as a novel intervention target to mitigate the detrimental impact of global temperature rise on vulnerable populations.

Over the past 2 decades, the microbiome has received increasing attention for the role that it plays in health and disease. Historically, the gut microbiome was of particular interest to pain scientists studying nociplastic visceral pain conditions given the anatomical juxtaposition of these microorganisms and the neuroimmune networks that drive pain in such diseases. More recently, microbiomes both inside and across the surface of the body have been recognized for driving sensory symptoms in a broader set of diseases. Microbiomes have never been a more popular topic in pain research, but to date, there has not been a systematic review of the preclinical microbiome pain literature. In this article, we identified all animal studies in which both the microbiome was manipulated and pain behaviors were measured. Our analysis included 303 unique experiments across 97 articles. Microbiome manipulation methods and behavioral outcomes were recorded for each experiment so that field-wide trends could be quantified and reported. This review specifically details the animal species, injury models, behavior measures, and microbiome manipulations used in preclinical pain research. From this analysis, we were also able to conclude how manipulations of the microbiome alter pain thresholds in naïve animals and persistent pain intensity and duration in cutaneous and visceral pain models. This review summarizes by identifying existing gaps in the literature and providing recommendations for how to best plan, implement, and interpret data collected in preclinical microbiome pain experiments.

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.

Horses are hindgut fermenters that harbor a complex intestinal microbiota (IM) which provides key enzymes aiding in the breakdown of complex carbohydrates present in their herbivorous diet. Therefore, these animals are deeply dependent on their IM for digestion and nutrition. Consequently, IM imbalances may result in alteration of fermentation patterns with impact on the animal health and the risk of disease. In this context, strategies for assisting the maintenance of a healthy IM in horses are of interest. However, there is limited research concerning the use of probiotics to improve hindgut fermentation and diet digestibility, with very few studies focusing on the use of lactobacilli strains from equine origin. Herein, we conducted independent fecal batch fermentations, using feces from "Asturcón" horses as inocula, added individually with four different lactobacilli strains (two strains of Lactobacillus acidophilus and two of Ligilactobacillus equi) isolated from this same horse breed. The impact on the gut microbiota composition was assessed by 16S rRNA gene profiling and the metabolic activity (production of short-chain fatty acids) by gas chromatography. The functionality of the lactobacilli strain was determined by monitoring in real-time gas production and determining changes in pH along incubation. L. acidophilus IPLA20127, promoted an increase in IM diversity and in the relative abundance of Lactobacillus genus, as well as higher butyric and valeric acid levels. This strain shows potential as probiotic supplement, without triggering acidification, nor promoting an increase of gas production or abrupt IM changes in our experimental model.