The gut microbiota has emerged as a fundamental regulator of sleep physiology, influencing neural, endocrine, and immune pathways through the gut-microbiota-brain axis (GMBA). This bidirectional communication system modulates neurotransmitter production, circadian rhythms, and metabolic homeostasis, while disruptions in microbial composition have been linked to sleep disorders, neuroinflammation, and systemic immune dysfunction. Recent findings suggest that gut dysbiosis contributes to sleep disturbances by altering serotonin, GABA, and short-chain fatty acid (SCFA) metabolism, with implications for neurodegenerative diseases, metabolic syndromes, and mood disorders. Additionally, the gut microbiota interacts with the endocrine and immune systems, shaping inflammatory responses and stress adaptation mechanisms. This review explores the intricate connections between sleep and the gut microbiota, integrating emerging research on microbiota-targeted therapies, such as probiotics, fecal microbiota transplantation (FMT), and chrononutrition, as potential interventions to restore sleep homeostasis and improve health outcomes
Chronic superficial gastritis (CSG) severely affects quality of life and can progress to worse gastric pathologies. Traditional Chinese Medicine (TCM) effectively treats CSG, as exemplified by Jinhong Tablets (JHT) with known anti-inflammatory properties, though their mechanism remains unclear. This study integrated network pharmacology, untargeted metabolomics, and gut microbiota analyses to investigate how JHT alleviates CSG. A rat CSG model was established and evaluated via H&E staining. We identified JHT's target profiles and constructed a multi-layer biomolecular network. Differential metabolites in plasma were determined by untargeted metabolomics, and gut microbiota diversity/composition in fecal and cecal samples was assessed via 16S rRNA sequencing. JHT markedly reduced gastric inflammation. Network pharmacology highlighted metabolic pathways, particularly lipid and nitric oxide metabolism, as essential to JHT's therapeutic effect. Metabolomics identified key differential metabolites including betaine (enhancing gut microbiota), phospholipids, and citrulline (indicating severity of CSG). Pathway enrichment supported the gut microbiota's involvement. Further microbiota
Background: Parkinson's disease remains a major neurodegenerative disorder with high misdiagnosis rates, primarily due to reliance on clinical rating scales. Recent studies have demonstrated a strong association between gut microbiota and Parkinson's disease, suggesting that microbial composition may serve as a promising biomarker. Although deep learning models based ongut microbiota show potential for early prediction, most approaches rely on single classifiers and often overlook inter-strain correlations or temporal dynamics. Therefore, there is an urgent need for more robust feature extraction methods tailored to microbiome data. Methods: We proposed BDPM (A Machine Learning-Based Feature Extractor for Parkinson's Disease Classification via Gut Microbiota Analysis). First, we collected gut microbiota profiles from 39 Parkinson's patients and their healthy spouses to identify differentially abundant taxa. Second, we developed an innovative feature selection framework named RFRE (Random Forest combined with Recursive Feature Elimination), integrating ecological knowledge to enhance biological interpretability. Finally, we designed a hybrid classification model to capture temporal
The global surge in the cases of gastric cancer has prompted an investigation into the potential of gut microbiota as a predictive marker for the disease. The alterations in gut diversity are suspected to be associated with an elevated risk of gastric cancer. This paper delves into finding the correlation between gut microbiota and gastric cancer, focusing on patients who have undergone total and subtotal gastrectomy. Utilizing data mining and statistical learning methods, an analysis was conducted on 16S-RNA sequenced genes obtained from 96 participants with the aim of identifying specific genera of gut microbiota associated with gastric cancer. The study reveals several prominent bacterial genera that could potentially serve as biomarkers assessing the risk of gastric cancer. These findings offer a pathway for early risk assessment and precautionary measures in the diagnosis of gastric cancer. The intricate mechanisms through which these gut microbiotas influence gastric cancer progression warrant further investigation. This research significantly aims to contribute to the growing understanding of the gut-cancer axis and its implications in disease prediction and prevention.
Alzheimer's disease (AD) has emerged as a progressively pervasive neurodegenerative disorder worldwide. Bile acids, synthesized in the liver and modified by the gut microbiota, play pivotal roles in diverse physiological processes, and their dysregulation in individuals with AD has been well-documented. However, the protein targets associated with microbiota-derived bile acids in AD have received limited attention. To address this gap, we conducted comprehensive thermal proteomic analyses to unravel and comprehend the protein targets affected by microbiota-derived bile acids in AD. Our investigation identified sixty-five unique proteins as potential targets of deoxycholic acid (DCA), a primary component of the bile acid pool originating from the gut microbiota. Particularly noteworthy among these proteins were Nicastrin and Casein kinase 1 epsilon. We found that DCA, through its interaction with the Nicastrin subunit of γ-secretase, significantly contributed to the formation of amyloid beta, a key hallmark of AD pathology. Additionally, We observed substantial elevations in the urine levels of four bile acids (DCA, GHCA, GHDCA, and GUDCA) in AD patients compared to healthy controls
Gut microbiota plays a crucial role in modulating pig development and health, and gut microbiota characteristics are associated with differences in feed efficiency. To answer open questions in feed efficiency analysis, biologists seek to retrieve information across multiple heterogeneous data sources. However, this is error-prone and time-consuming work since the queries can involve a sequence of multiple sub-queries over several databases. We present an implementation of an ontology-based Swine Gut Microbiota Federated Query Platform (SGMFQP) that provides a convenient, automated, and efficient query service about swine feeding and gut microbiota. The system is constructed based on a domain-specific Swine Gut Microbiota Ontology (SGMO), which facilitates the construction of queries independent of the actual organization of the data in the individual sources. This process is supported by a template-based query interface. A Datalog+-based federated query engine transforms the queries into sub-queries tailored for each individual data source, and an automated workflow orchestration mechanism executes the queries in each source database and consolidates the results. The efficiency of
Fecal Microbiota Transplant (FMT) is an FDA approved treatment for recurrent Clostridium difficile infections, and is being explored for other clinical applications, from alleviating digestive and neurological disorders, to priming the microbiome for cancer treatment, and restoring microbiomes impacted by cancer treatment. Quantifying the extent of engraftment following an FMT is important in determining if a recipient didn't respond because the engrafted microbiome didn't produce the desired outcomes (a successful FMT, but negative treatment outcome), or the microbiome didn't engraft (an unsuccessful FMT and negative treatment outcome). The lack of a consistent methodology for quantifying FMT engraftment extent hinders the assessment of FMT success and its relation to clinical outcomes, and presents challenges for comparing FMT results and protocols across studies. Here we review 46 studies of FMT in humans and model organisms and group their approaches for assessing the extent to which an FMT engrafts into three criteria: 1) Chimeric Asymmetric Community Coalescence investigates microbiome shifts following FMT engraftment. 2) Donated Microbiome Indicator Features tracks donated m
Mammalian gut microbiomes are essential for host functions like digestion, immunity, and nutrient utilization. This study examines the gut microbiome of horses, donkeys, and their hybrids, mules and hinnies, to explore the role of microbiomes in hybrid vigor. We performed whole-genome sequencing on rectal microbiota from 18 equids, generating detailed microbiome assemblies. Our analysis revealed significant differences between horse and donkey microbiomes, with hybrids showing a pronounced maternal resemblance. Notably, Firmicutes were more abundant in the horse-maternal group, while Fibrobacteres were richer in the donkey-maternal group, indicating distinct digestive processes. Functional annotations indicated metabolic differences, such as protein synthesis in horses and energy metabolism in donkeys. Machine learning predictions of probiotic species highlighted potential health benefits for each maternal group. This study provides a high-resolution view of the equid gut microbiome, revealing significant taxonomic and metabolic differences influenced by maternal lineage, and offers insights into microbial contributions to hybrid vigor.
We present q2-fmt, a QIIME 2 plugin that provides diverse methods for assessing the extent of microbiome engraftment following fecal microbiota transplant. The methods implemented here were informed by a recent literature review on approaches for assessing FMT engraftment, and cover aspects of engraftment including Chimeric Asymmetric Community Coalescence, Donated Microbiome Indicator Features, and Temporal Stability. q2-fmt is free for all use, and detailed documentation illustrating worked examples on a real-world data set are provided in the project's documentation.
Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. We generated a germ-free mouse model of Alzheimer's disease and discovered a drastic reduction of cerebral Ab amyloid pathology when compared to control Alzheimer's disease animals with intestinal microbiota. Sequencing bacterial 16S rRNA from fecal samples revealed a remarkable shift in the gut microbiota of conventionally-raised Alzheimer's disease mice as compared to healthy, wild-type mice. Colonization of germ-free Alzheimer mice with harvested microbiota from conventionally-raised Alzheimer mice dramatically increased cerebral Ab pathology. In contrast, colonization with microbiota from control wild-type mice was ineffective in increasing cerebral Ab levels. Our results indicate a microbial involvement in the development of Alzheimer's disease pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.
Logarithmic growth-rates are fundamental observables for describing ecological systems and the characterization of their distributions with analytical techniques can greatly improve their comprehension. Here a neutral model based on a stochastic differential equation with demographic noise, which presents a closed form for these distributions, is used to describe the population dynamics of microbiota. Results show that this model can successfully reproduce the log-growth rate distribution of the considered abundance time-series. More significantly, it predicts its temporal dependence, by reproducing its kurtosis evolution when the time lag $τ$ is increased. Furthermore, its typical shape for large $τ$ is assessed, verifying that the distribution variance does not diverge with $τ$. The simulated processes generated by the calibrated stochastic equation and the analysis of each time-series, taken one by one, provided additional support for our approach. Alternatively, we tried to describe our dataset by using a logistic neutral model with an environmental stochastic term. Analytical and numerical results show that this model is not suited for describing the leptokurtic log-growth rat
The gut-muscle axis has been proposed to link gut microbiota with skeletal muscle physiology, yet its universality across livestock species remains unclear. Using aged laying hens, a livestock model with a relatively short digestive tract, we examined the gut microbiota, faecal metabolome, and breast-muscle metabolome by integrative multi-omics analyses in hens fed a Caldifermentibacillus hisashii-containing fermented feed or a control diet. Non-metric multidimensional scaling revealed clear separation of the microbial community between groups (stress = 0.0097), characterised by a marked expansion of Lactobacillus with the administration of the fermented feed. Variance partitioning showed that the 16S microbiota shared substantial variance with both the faecal (shared R2 adj = 0.54) and muscle (shared R2 adj = 0.48) metabolomes, and partial dbRDA demonstrated that the faecal-to-muscle metabolite association was largely retained after controlling for 16S (direct R2 = 0.538, partial R2 = 0.485), consistent with faecal metabolites acting as an integral layer linking microbiota to muscle. Cliff's delta-based selection showed depletion of proteolytic taxa and faecal amino acids, and red
Fescue toxicity causes reduced growth and reproductive issues in cattle grazing endophyte-infected tall fescue. To characterize the gut microbiota and its response to fescue toxicosis, we collected fecal samples before and after a 30-days toxic fescue seeds supplementation from eight Angus Simmental pregnant cows and heifers. We sequenced the 16 metagenomes using the whole-genome shotgun approach and generated 157 Gbp of metagenomic sequences. Through de novo assembly and annotation, we obtained a 13.1 Gbp reference contig assembly and identified 22 million microbial genes for cattle rectum microbiota. We discovered a significant reduction of microbial diversity after toxic seed treatment (P<0.01), suggesting dysbiosis of the microbiome. Six bacterial families and 31 species are significantly increased in the fecal microbiota (P-adj<0.05), including members of the top abundant rumen core taxa. This global elevation of rumen microbes in the rectum microbiota suggests a potential impairment of rumen microbiota under fescue toxicosis. Among these, Ruminococcaceae bacterium P7, an important species accounting for ~2% of rumen microbiota, was the most impacted with a 16-fold incre
The gut-brain axis has emerged as a key player in the regulation of brain function and cognitive health. Gut microbiota dysbiosis has been observed in preclinical models of Alzheimer's disease and patients. Manipulating the composition of the gut microbiota enhances or delays neuropathology and cognitive deficits in mouse models. Accordingly, the health status of the animal facility may strongly influence these outcomes. In the present study, we longitudinally analysed the faecal microbiota composition and amyloid pathology of 5XFAD mice housed in a specific opportunistic pathogen-free (SOPF) and a conventional facility. The composition of the microbiota of 5XFAD mice after aging in conventional facility showed marked differences compared to WT littermates that were not observed when the mice were bred in SOPF facility. The development of amyloid pathology was also enhanced by conventional housing. We then transplanted faecal microbiota (FMT) from both sources into wild-type (WT) mice and measured memory performance, assessed in the novel object recognition test, in transplanted animals. Mice transplanted with microbiota from conventionally bred 5XFAD mice showed impaired memory pe
This paper introduces a rectified and renormalized Fisher-Bingham model for compositional data with zeros, motivated in part by the presence of zeros in microbiota studies. The approach represents compositions through a square-root transformation that maps data to the positive orthant of the unit sphere, and models them via a latent Fisher-Bingham followed by a deterministic transformation that induces exact zeros. This construction yields a coherent likelihood without requiring zero imputation or separate modeling of zero and nonzero components. Parameter estimation is performed using a Monte Carlo expectation-maximization algorithm that accommodates the latent structure. We further develop a score test for detecting structured differences in composition across groups, providing a parametric alternative to commonly used distance-based methods. Simulation studies demonstrate that the proposed method closely approximates the induced distribution and achieves higher power for detecting structured compositional changes, particularly when observations include many zero-valued components. An application to a dietary intervention study illustrates that the method identifies meaningful mi
The rapid expansion of biomedical publications creates challenges for organizing knowledge and detecting emerging trends, underscoring the need for scalable and interpretable methods. Common clustering and topic modeling approaches such as K-means or LDA remain sensitive to initialization and prone to local optima, limiting reproducibility and evaluation. We propose a reformulation of a convex optimization based clustering algorithm that produces stable, fine-grained topics by selecting exemplars from the data and guaranteeing a global optimum. Applied to about 12,000 PubMed articles on aging and longevity, our method uncovers topics validated by medical experts. It yields interpretable topics spanning from molecular mechanisms to dietary supplements, physical activity, and gut microbiota. The method performs favorably, and most importantly, its reproducibility and interpretability distinguish it from common clustering approaches, including K-means, LDA, and BERTopic. This work provides a basis for developing scalable, web-accessible tools for knowledge discovery.
The state space is a fundamental concept for describing the trajectory of a dynamic system. Depending on its form, it can highlight certain changes over time while ignoring others. This is particularly the case for the spaces associated with theoretical ecology models, notably the generalized Lotka-Volterra (gLV) model, which allows the modeling of interacting populations. The fixed-dimension state space classically used in gLV models does not account for the effective renewal of species through addition, removal, or mutation. To address this limitation, we propose a new variable-base state space, introduced in a previous study. This framework leads to a reformulation of the gLV model within the context of hybrid dynamical systems. To illustrate the approach, we apply the proposed model to the gut microbiota, particularly in the context of bacteriotherapy following antibiotic treatment.
A holobiont is made up of a host organism together with its microbiota. In the context of animal breeding, the holobiont can be viewed as the single unit upon which selection operates. Therefore, integrating microbiota data into genomic prediction models may be a promising approach to improve predictions of phenotypic and genetic values. Nevertheless, there is a paucity of hologenomic transgenerational data to address this hypothesis, and thus to fill this gap, we propose a new simulation framework. Our approach, an R Implementation of a Transgenerational Hologenomic Model-based Simulator (RITHMS) is an open-source package. It builds upon simulated transgenerational genotypes from the Modular Breeding Program Simulator (MoBPS) package and incorporates distinctive characteristics of the microbiota, notably vertical and horizontal transmission as well as modulation due to the environment and host genetics. In addition, RITHMS can account for a variety of selection strategies and is adaptable to different genetic architectures. We simulated transgenerational hologenomic data using RITHMS under a wide variety of scenarios, varying heritability, microbiability, and microbiota transmissi
Background: Morbid obesity is associated with metabolic alterations and the onset of type 2 diabetes. Patients who undergo a malabsorptive bariatric surgery show an important improvement in several clinical variables and a modification in the gut microbiota balance. In this study, we aimed to identify bacteria related to changes in the body mass index of patients who underwent a bariatric surgery and their relationship with nutrients intake. Results: There were differences in bacterial diversity in the gut microbiota of patients that underwent a bariatric surgery. The Shannon and Simpson indexes decrease after the surgery (p < 0.001) and the beta diversity indexes (Bray-Curtis, Weighted and Unweighted UniFrac) showed differences when comparing pre- and post-surgery (p = 0.001). The abundance of a species in the genus Coprococcus correlated positively with the intake of magnesium and thiamin in post-surgery individuals (rho = 0.816, pFDR = 0.029 and rho = 0.812, pFDR = 0.029, respectively) and was related to BMI in both groups (p = 0.043 pre-surgery and p = 0.036 post-surgery). The abundances of several bacteria belonging to the order Clostridiales, as well as an enrichment of vi
Jinhong tablet (JHT), a traditional Chinese medicine made from four herbs, effectively treats chronic superficial gastritis (CSG) by soothing the liver, relieving depression, regulating qi, and promoting blood circulation. However, its pharmacokinetics are underexplored. This study investigates JHT's pharmacokinetics in normal rats and its differences in normal, CSG, and intestinal microbial disorder rats. A quantitative method for seven active ingredients in rat plasma was established using UPLC-TQ-MS/MS. After administering various JHT doses, plasma concentrations were measured to assess pharmacokinetics in normal rats. The pharmacokinetics of four main ingredients were compared in normal, CSG, and fecal microbiota transplantation (FMT) rats. Intestinal microbial changes were evaluated by high-throughput sequencing. Spearman correlation analysis linked ingredient exposure to gut microbiota disturbances. The method showed good linearity, precision, accuracy, extraction recovery, and stability. In normal rats, all seven ingredients were rapidly absorbed. Tetrahydropalmatine, corydaline, costunolide, and rhamnosylvitexin had good exposure, while dehydrocorydaline, allocryptopine, an