Integrative analysis of the mouse cecal microbiome across diet, age, and weight in the diverse BXD population

Microbiome-gut-liver axis in chronic inflammation and cancer immunotherapy: Multi-omics Insights and a translational roadmap toward personalized medicine.

To investigate whether elastic fiber content in the corpus cavernosum (CC), corpus spongiosum (CS) and tunica albuginea (TA) of the rabbit penis undergoes modifications with age. Rabbits were sacrificed, in groups of ten animals each, at 30, 120, 240, and 730 days of age. Histological sections were obtained from the penile middle shaft and were stained with Weigert's resorsin fuchsin. The content of elastic fibers was determined using stereological methods, and was expressed as volume fraction. At 730 days of age, elastic fiber content was increased by 54% (p<0.004), 78% (p<0.004), and 87% (p<0.004) in the TA, CC, and CS, respectively, compared with animals aged 30 days. After 30 days of age, the concentration gradually and significantly increased until 240 days of age. In 730-day old animals, the concentration, compared with the previous age group, was unchanged in the CC and decreased by 20% (p<0.004) in the TA. Elastic fiber contents in the rabbit penis correlate with properties of penile tissues. Although after one month of age there is a gradual increase in these concentrations, in two-year old animals this trend is interrupted, which suggests that this could be an early alteration due to senescence.

812 AGE-RELATED CHANGES IN THE CONCENTRATION OF ELASTIC FIBERS IN DIFFERENT REGIONS OF THE RABBIT PENIS

O objetivo deste trabalho foi determinar parâmetros genéticos do peso desde o nascimento até 730 dias de idade na raça Indubrasil. Registros de peso (82.481) de 20.890 animais do nascimento aos 730 dias de idade foram utilizados. Os parâmetros genéticos foram determinados por meio de regressão aleatória. Amostras da distribuição a posteriori dos parâmetros de interesse foram obtidas com o amostrador de Gibbs. Polinômios de Legendre ou segmentados foram utilizados para modelar a trajetória média de crescimento. Os efeitos genético aditivo direto e de ambiente permanente direto foram modelados por polinômios de Legendre. Um polinômio segmentado linear-linear, com nó aos 251 dias de idade, ajustou a trajetória média. Polinômios de Legendre quadráticos e quínticos ajustaram, respectivamente, os efeitos genético aditivo e de ambiente permanente. Três classes de idade foram suficientes para modelar a heterocedasticidade residual. Na maior parte do intervalo considerado, as médias a posteriori da herdabilidade foram crescentes, com valores entre 0,10 e 0,45; a proporção da variância de ambiente permanente em relação à variância fenotípica foi constante, em torno de 0,48; e as correlações genéticas dos pesos em diferentes idades foram altas, acima de 0,60. Há variabilidade genética quanto ao peso na raça Indubrasil, e a seleção pode aumentar a média desta característica.

Metabolic Associated Steatosis Liver Disease (MASLD) and its advanced form, Metabolic Associated Steatohepatitis (MASH), represent growing global health concerns closely linked to obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. The gut microbiome has emerged as a key modulator in MASLD pathogenesis through the gut–liver axis, influencing hepatic fat accumulation, inflammation, and fibrosis via microbial metabolites and immune responses. Dysbiosis–characterized by altered microbial diversity and composition–contributes to hepatic lipid dysregulation, systemic inflammation, and impaired bile acid signaling. Metabolites such as short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and ethanol play critical roles in disease progression. Recent innovations in precision medicine, including microbiome profiling, metabolomics, and genomics, offer promising diagnostic and therapeutic strategies. Targeted probiotics, fecal microbiota transplantation (FMT), and personalized dietary interventions are under investigation for modulating the gut microbiome. This systematic review, conducted in accordance with PRISMA 2020 guidelines, is the first to comprehensively integrate both animal and human studies on MASLD/MASH-related gut microbiome alterations. It uniquely synthesizes microbial taxa, functional metabolites, and region-specific patterns–including data from underrepresented MENA populations. Eligible studies from PubMed, Scopus, and Web of Science evaluated microbial composition, metabolite profiles, and associations with steatosis, inflammation, and fibrosis. The findings underscore the diagnostic and therapeutic potential of microbiome modulation and emphasize the need for longitudinal, mechanistically driven studies. This systematic review is the first to integrate both animal and human studies on MASLD/MASH-related gut microbiome alterations. Unlike previous reviews, it uniquely emphasizes microbial taxa, functional metabolites, and region-specific patterns, including underrepresented MENA populations. By synthesizing findings from diverse cohorts, this review highlights diagnostic and therapeutic opportunities while identifying persistent gaps in longitudinal data, regional representation, and multi-omics integration.

Emerging evidences about gut-microbial modulation have been accumulated in the treatment of nonalcoholic fatty liver disease (NAFLD). We evaluated the effect of Bifidobacterium breve and Bifidobacterium longum on the NAFLD pathology and explore the molecular mechanisms based on multi-omics approaches. Human stool analysis [healthy subjects (n = 25) and NAFLD patients (n = 32)] was performed to select NAFLD-associated microbiota. Six-week-old male C57BL/6 J mice were fed a normal chow diet (NC), Western diet (WD), and WD with B. breve (BB) or B. longum (BL; 109 CFU/g) for 8 weeks. Liver/body weight ratio, histopathology, serum/tool analysis, 16S rRNA-sequencing, and metabolites were examined and compared. The BB and BL groups showed improved liver histology and function based on liver/body ratios (WD 7.07 ± 0.75, BB 5.27 ± 0.47, and BL 4.86 ± 0.57) and NAFLD activity scores (WD 5.00 ± 0.10, BB 1.89 ± 1.45, and BL 1.90 ± 0.99; p < 0.05). Strain treatment showed ameliorative effects on gut barrier function. Metagenomic analysis showed treatment-specific changes in taxonomic composition. The community was mainly characterized by the significantly higher composition of the Bacteroidetes phylum among the NC and probiotic-feeding groups. Similarly, the gut metabolome was modulated by probiotics treatment. In particular, short-chain fatty acids and tryptophan metabolites were reverted to normal levels by probiotics, whereas bile acids were partially normalized to those of the NC group. The analysis of gene expression related to lipid and glucose metabolism as well as the immune response indicated the coordinative regulation of β-oxidation, lipogenesis, and systemic inflammation by probiotic treatment. BB and BL attenuate NAFLD by improving microbiome-associated factors of the gut-liver axis.

Huanglian Wendan decoction alleviates metabolic syndrome by reprogramming macrophage polarization: Evidence from multi-omics integration.

The polyunsaturated fatty acid composition of human brain changes, as well as progressively decreases, with age. To determine if whole brain rat lipid shows similar changes with age, rats born to mothers fed semi-synthetic diets were raised on the same diet as their mothers for varying periods prior to sacrifice. Whole brain lipid composition was determined for female offspring, fed diets containing 20% w (by weight) of either lard or safflower oil, from age 6 days to 730 days. The percentage of 20:4omega6 and 22:6omega6 decreased with age; as in man these changes were compensated for largely by increases in 18:1omega9. In contrast, 22:6omega3 rose gradually from 6 to 730 days of age. Varying the degree of unsaturation and/or the amount of dietary fat, with the exception of lard, did not influence the fatty acid composition of whole brain lipid or of the two major phospholipids, phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC). Lard was found to contain trace amounts of 22:5omega3; this acid was avidly retained in the brain accompanied by corresponding decreases in 22:5omega6. The functional significance of the observed age-related brain lipid changes is unknown; it is likely that the lipid changes are in some way related to the deterioration of the central nervous system with time.

The weight records from Simmental beef cattle were used in a genetic evaluation of growth with or without the inclusion of animals obtained by embryo transfer. A multi-trait model in which embryo transfer individuals were excluded (MTM1) contained 29,510 records from 10,659 animals, while another model without exclusion of these animals (MTM2) contained 62,895 weight records from 23,160 animals. The weight records were adjusted for ages of 100, 205, 365, 450, 550 and 730 days. The (co)variance components and genetic parameters were estimated by the restricted maximum likelihood method. The (co)variance components were similar in both models, except for maternal permanent environment variance. Direct heritabilities (h2d) in MTM1 were 0.04, 0.11, 0.20, 0.27, 0.31 and 0.42, while in MTM2 they were 0.11, 0.11, 0.17, 0.21, 0.22 and 0.26 for 100, 205, 365, 450, 550 and 730 days of age, respectively. Estimates of h2d in MTM1 were higher than in MTM2 for the weight at 365 days of age. Genetic correlations between weights in both models ranged from moderate to high, suggesting that these traits may be determined mainly by the same genes. Animals from embryo transfer may be included in the genetic evaluation of Simmental beef cattle in Brazil; this inclusion may provide potential gains in accuracy and genetic gains by reducing the interval between generations.

BackgroundNonalcoholic Fatty Liver Disease(NAFLD)refers to a spectrum of diseases ranging from simple liver steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Bidirectional cross-talk between the gut-liver axis plays an important role in the pathogenesis of NAFLD. To learn more about the gut-liver axis in NAFLD, this study aims to provide a comprehensive analysis from a bibliometric perspective.MethodLiterature related to the gut-liver axis in NAFLD from 1989 to 2022 was extracted from the Web of Science Core Collection. Based on Microsoft Excel, CiteSpace and Vosviewer, we conducted to analyze the number of publications, countries/regions, institutions, authors, journals, references, and keywords.ResultsA total of 1,891 literature since 2004 was included, with the rapid growth of the number of papers on the gut-liver axis in NAFLD annually. These publications were mainly from 66 countries and 442 institutions. Of the 638 authors analyzed, Bernd Schnabl was the one with the most publications, and Patrice D. Cani was the one with the most co-citations. International Journal of Molecular Sciences is the journal with the most articles published, and Hepatology is the journal with the most citations. The most common keywords are gut microbiota, inflammation, and insulin instance, which are current research hotspots. Short-chain fatty acid, in vitro, randomized controlled trial in clinical, and diabetes mellitus represent the research frontiers in this field and are in a stage of rapid development.ConclusionThis is the first study to conduct a comprehensive bibliometric analysis of publications related to the gut-liver axis in NAFLD. This study reveals that gut microbiota, inflammation, insulin resistance, short-chain fatty acids, and randomized controlled trial will be the hotspots and new trends in the gut-liver axis in NAFLD research, which could provide researchers with key research information in this field and is helpful for further exploration of new research directions.

BackgroundMechanistic research establishing a causal relationship between gut dysbiosis and developmental origins of health and disease (DOHaD) is lacking. The ontogeny of many liver genes is modulated by distinct epigenetic mechanisms through microbial metabolites, such as histone acetylation and short‐chain fatty acids (SCFAs). Early life exposure to bisphenol A (BPA) has been linked to epigenetic reprogramming in adults, but little is known regarding the potentially persistent effects of other environmental toxicants (e.g. polybrominated diphenyl ethers [PBDEs] and polychlorinated biphenyls [PCBs]) on the gut‐liver axis. The present study tested the hypothesis that neonatal oral exposure to these compounds causes persistent dysbiosis, leading to epigenetic reprogramming of hepatic xenobiotic biotransformation genes by microbial metabolites.Experimental DesignMale and female C57BL/6J mouse pups were sublingually exposed to corn oil, BDE‐99, BPA, or Fox River PCB mixture once daily at postnatal days (PND) 2–4. Feces and host tissues were collected at PND 5 and 60 (n=5 per group). Microbial DNA from feces and intestines (duodenum, jejunum, ileum, and large intestine) was subjected to 16S rDNA sequencing. Whole transcriptome sequencing (RNA‐Seq) and location of epigenetic marks (ChIP‐Seq) were conducted in livers of PND 60 mice. SCFAs were quantified in livers of PND 60 mice using gas chromatography‐mass spectrometry (GC‐MS).ResultsNeonatal chemical exposure persistently decreased the richness of the bacterial community (alpha diversity) in feces of adult mice. Interestingly, BDE‐99, but not BPA or PCB, profoundly increased the percentage of the SCFA‐generating Akkermensia muciniphilia in both male and female PND60 mice (0.55%‐6%) in duodenum, jejunum, large intestine, and feces. Corresponding to the increase in A. muciniphila, in BDE‐99 neonatal exposed mice, there was a persistent increase in the relative abundance of the hepatic SCFAs succinate and lactate, as well as an increasing trend in the known HDAC inhibitor acetate in adult age. In addition, adult male mice that were neonatally exposed to BDE‐99 had 12,606 more peaks for the permissive gene transcription mark histone 3 lysine 27 acetylation (H3K27ac; p&lt;0.01; MACS2) associated with 4,495 protein‐coding genes (threshold: ±10kb of the gene loci; PAVIS). Examples of these genes include cytochrome P450s as well as genes involved in circadian entrainment.ConclusionNeonatal exposure to BDE‐99, BPA, and PCBs persistently altered the gut microbiome composition, correlating with altered hepatic SCFAs and epigenetic reprogramming, demonstrating the importance of the gut‐liver axis in DOHaD.Support or Funding InformationFunding provided by NIH grants P30ES007033 and P30 ES023512‐04S2 (Center admin supplement), as well as GM111381.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Tale of Two Fibers: A Liver Twist!

The complex, bidirectional communication between the gut and the lungs, known as the "gut-lung axis," profoundly influences host immune homeostasis and the pathogenesis of respiratory diseases. In recent years, multi-omics approaches, including metagenomics, metabolomics, and metatranscriptomics, have emerged as the core driving force for unraveling the complexity of this interorgan cross talk network. This review aims to systematically summarize the current omics-based evidence in the field of the gut-lung axis. We highlight key communication mechanisms discovered through multi-omics integration, particularly how gut microbiota-derived metabolites, exemplified by short-chain fatty acids (SCFAs), mediate distal immune regulation. Concurrently, we consolidate omics evidence from the contexts of respiratory infectious diseases, chronic lung disorders, and aging, systematically delineating the impact of gut dysbiosis on pulmonary pathophysiology via the gut-lung axis and emphasizing the feasibility of disease management in patients with lung diseases by modulating the gut microbiota. Although omics technologies have significantly advanced our understanding of this field, the challenge of effectively integrating vast, heterogeneous data and transitioning from "correlation" to "causation" remains a primary hurdle. By reviewing and discussing the current omics evidence in the gut-lung axis, this paper aims to provide new perspectives for future mechanistic explorations and clinical translation strategies.

Identification of causal variants and genes underlying genome-wide association study (GWAS) loci is essential to understand the biology of alcohol use disorder (AUD) and drinks per week (DPW). Multi-omics integration approaches have shown potential for fine mapping complex loci to obtain biological insights to disease mechanisms. In this study, we use multi-omics approaches, to fine-map AUD and DPW associations at single SNP resolution to demonstrate that rs56030824 on chromosome 11 significantly reduces SPI1 mRNA expression in myeloid cells and lowers risk for AUD and DPW. Our analysis also identifies MAPT as a candidate causal gene specifically associated with DPW. Genes prioritized in this study show overlap with causal genes associated with neurodegenerative disorders. Multi-omics integration analyses highlight, genetic similarities and differences between alcohol intake and disordered drinking, suggesting molecular heterogeneity that might inform future targeted functional and cross-species studies.

Subacute dimethylated monothioarsenate (DMMTA) exposure induces hepatotoxicity and disrupts the gut microbiota-bile acid-liver axis: A multi-omics study in mice.