The genetic diversity and populational specificity of the human gut virome at single-nucleotide resolution.

Background: Large-scale characterization of gut viral genomes provides strain-resolved insights into host-microbe interactions. However, existing viral genomes are mainly derived from Western populations, limiting our understanding of global gut viral diversity and functional variations necessary for personalized medicine and addressing regional health disparities.

Results: Here, we introduce the Chinese Gut Viral Reference (CGVR) set, consisting of 120,568 viral genomes from 3234 deeply sequenced fecal samples collected nationwide, covering 72,751 viral operational taxonomic units (vOTUs), nearly 90% of which are likely absent from current databases.

Dissecting the causal association of periodontitis with biological aging and its underlying mechanisms: findings from Mendelian randomization and integrative genetic analysis.

Purpose: Chronic low-grade inflammation is linked to the biology of aging; however, evidence supporting a causal relationship between periodontitis-a dysbiotic biofilm-initiated inflammatory disease-and accelerated aging remains limited. This study investigated the causality between periodontitis and biological aging and identified potentially shared genomic loci, genes, and pathways.

Methods: We conducted a 2-sample Mendelian randomization (MR) analysis to explore the causality of periodontitis on age acceleration measures (DNAm PhenoAge acceleration, GrimAge acceleration, Hannum age acceleration, and intrinsic epigenetic age acceleration) using a dataset from genome-wide association studies of European ancestry populations.

Gut Microbiota as a Mediator Between Intestinal Fibrosis and Creeping Fat in Crohn's Disease.

Intestinal stricture remains one of the most challenging complications in Crohn's disease, and its underlying mechanisms are poorly understood. Accumulating evidence suggests that gut microbiota is significantly altered in stenotic intestines and may play a key role in the development of fibrogenesis in Crohn's disease. Additionally, the presence of hypertrophic mesenteric adipose tissue, also known as creeping fat, is closely correlated with intestinal stricture and fibrosis.

Integrating multi-omics data to reveal the host-microbiota interactome in inflammatory bowel disease.

Numerous studies have accelerated the knowledge expansion on the role of gut microbiota in inflammatory bowel disease (IBD). However, the precise mechanisms behind host-microbe cross-talk remain largely undefined, due to the complexity of the human intestinal ecosystem and multiple external factors. In this review, we introduce the concept to systematically summarize how intestinal dysbiosis is involved in IBD pathogenesis in terms of microbial composition, functionality, genomic structure, transcriptional activity, and downstream proteins and metabolites.

Non-differential gut microbes contribute to hypertension and its severity through co-abundances: A multi-regional prospective cohort study.

Microbial dysbiosis, characterized by an imbalanced microbial community structure and function, has been linked to hypertension. While prior research has primarily focused on differential abundances, our study highlights the role of non-differential microbes in hypertension. We propose that non-differential microbes contribute to hypertension through their ecological interactions, as defined by co-abundances (pairs of microbes exhibiting correlated abundance patterns).

Association Between Chewing Capacity and Mortality Risk: The Role of Diet and Ageing.

Aim: Masticatory dysfunction due to tooth loss is a potentially modifiable risk for mortality, but the pathway behind that remains to be investigated. This prospective study aimed to examine the role of diet and ageing in the associations between chewing capacity and long-term mortality.

Methods: Data were obtained from participants (aged ≥ 20) in the National Health Nutritional and Health Survey (NHANES 1999-2010, n = 22,900).

Gene expression profiling in PBMCs for acute rejection in lung transplant recipients reveals myeloid responses.

The acute rejection (AR) diagnosis depends on transbronchial biopsy, which is semi-invasive and not easily performed Our study used the Nanostring gene expression technology on PBMCs obtained from lung transplant recipients (LTRs) to search for biomarkers. We identified distinct differential gene profiles between patients with stable status (STA) and AR. Subsequently, we independently evaluated monocyte compositions in PBMCs using flow cytometry and assessed the levels of 7 chemokines in serum using Luminex.

An atlas of the shared genetic architecture between atopic and gastrointestinal diseases.

Comorbidity among atopic diseases (ADs) and gastrointestinal diseases (GIDs) has been repeatedly demonstrated by epidemiological studies, whereas the shared genetic liability remains largely unknown. Here we establish an atlas of the shared genetic architecture between 10 ADs or related traits and 11 GIDs, comprehensively investigating the comorbidity-associated genomic regions, cell types, genes and genetically predicted causality. Although distinct genetic correlations between AD-GID are observed, including 14 genome-wide and 28 regional correlations, genetic factors of Crohn's disease (CD), ulcerative colitis (UC), celiac disease and asthma subtypes are converged on CD4 T cells consistently across relevant tissues.

Genome-wide meta-analysis associates donor-recipient non-HLA genetic mismatch with acute cellular rejection post-liver transplantation.

Background: Acute cellular rejection (ACR) remains a common complication causing significant morbidity post-liver transplantation. Non-human leukocyte antigen (non-HLA) mismatches were associated with an increased risk of ACR in kidney transplantation. Therefore, we hypothesized that donor-recipient non-HLA genetic mismatch is associated with increased ACR incidence post-liver transplantation.

Multi-Omics Biomarkers for Predicting Efficacy of Biologic and Small-Molecule Therapies in Adults With Inflammatory Bowel Disease: A Systematic Review.

The heterogeneity and suboptimal efficacy of biological treatments and small molecule drugs necessitate their precise selection based on biomarkers that predict therapeutic responses in inflammatory bowel disease. Recent studies have identified numerous novel biomarkers predictive of responses to biologics and small molecule modulators, utilizing a variety of omics approaches in inflammatory bowel disease. In this review, we systematically examine baseline omics biomarkers that predict responses to biological therapies and small molecule drugs, drawing on literature from PubMed.

Multiomics reveals microbial metabolites as key actors in intestinal fibrosis in Crohn's disease.

Intestinal fibrosis is the primary cause of disability in patients with Crohn's disease (CD), yet effective therapeutic strategies are currently lacking. Here, we report a multiomics analysis of gut microbiota and fecal/blood metabolites of 278 CD patients and 28 healthy controls, identifying characteristic alterations in gut microbiota (e.g.

Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content.

Genetic susceptibility to metabolic associated fatty liver disease (MAFLD) is complex and poorly characterized. Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors. We performed genome-wide association study (GWAS) on two noninvasive definitions of hepatic fat content: magnetic resonance imaging proton density fat fraction (MRI-PDFF) in 16,050 participants and fatty liver index (FLI) in 388,701 participants from the United Kingdom (UK) Biobank (UKBB).

Developing a Machine-Learning Prediction Model for Infliximab Response in Crohn's Disease: Integrating Clinical Characteristics and Longitudinal Laboratory Trends.

Background: Achieving long-term clinical remission in Crohn's disease (CD) with antitumor necrosis factor α (anti-TNF-α) agents remains challenging.

Aims: This study aims to establish a prediction model based on patients' clinical characteristics using a machine-learning approach to predict the long-term efficacy of infliximab (IFX).

Methods: Three cohorts comprising 746 patients with CD were included from 3 inflammatory bowel disease (IBD) centers between June 2013 and January 2022.

Mucosal host-microbe interactions associate with clinical phenotypes in inflammatory bowel disease.

Disrupted host-microbe interactions at the mucosal level are key to the pathophysiology of IBD. This study aimed to comprehensively examine crosstalk between mucosal gene expression and microbiota in patients with IBD. To study tissue-specific interactions, we perform transcriptomic (RNA-seq) and microbial (16S-rRNA-seq) profiling of 697 intestinal biopsies (645 derived from 335 patients with IBD and 52 from 16 non-IBD controls).

Temporal colonization and metabolic regulation of the gut microbiome in neonatal oxen at single nucleotide resolution.

The colonization of microbes in the gut is key to establishing a healthy host-microbiome symbiosis for newborns. We longitudinally profiled the gut microbiome in a model consisting of 36 neonatal oxen from birth up to 2 months postpartum and carried out microbial transplantation to reshape their gut microbiome. Genomic reconstruction of deeply sequenced fecal samples resulted in a total of 3931 metagenomic-assembled genomes from 472 representative species, of which 184 were identified as new species when compared with existing databases of oxen.

Crohn's Disease-Associated Pathogenic Mutation in the Manganese Transporter ZIP8 Shifts the Ileal and Rectal Mucosal Microbiota Implicating Aberrant Bile Acid Metabolism.

Background: A pathogenic mutation in the manganese transporter ZIP8 (A391T; rs13107325) increases the risk of Crohn's disease. ZIP8 regulates manganese homeostasis and given the shared need for metals between the host and resident microbes, there has been significant interest in alterations of the microbiome in carriers of ZIP8 A391T. Prior studies have not examined the ileal microbiome despite associations between ileal disease and ZIP8 A391T.

Early microbial intervention reshapes phenotypes of newborn Bos taurus through metabolic regulations.

Background: The rumen of neonatal calves has limited functionality, and establishing intestinal microbiota may play a crucial role in their health and performance. Thus, we aim to explore the temporal colonization of the gut microbiome and the benefits of early microbial transplantation (MT) in newborn calves.

Results: We followed 36 newborn calves for 2 months and found that the composition and ecological interactions of their gut microbiomes likely reached maturity 1 month after birth.

promotes intestinal epithelial IL-18 production through activation of the HIF1α pathway.

Introduction: Intestinal epithelial cells produce interleukin-18 (IL-18), a key factor in promoting epithelial barrier integrity. Here, we analyzed the potential role of gut bacteria and the hypoxia-inducible factor 1α (HIF1α) pathway in regulating mucosal expression in inflammatory bowel disease (IBD).

Methods: Mucosal samples from patients with IBD ( = 760) were analyzed for bacterial composition, levels and HIF1α pathway activation.

Multi-omic insight into the molecular networks of mitochondrial dysfunction in the pathogenesis of inflammatory bowel disease.

Background: Mitochondrial dysfunction has been linked to the development of inflammatory bowel disease (IBD), but the genetic pathophysiology was not fully elucidated. We employed Mendelian randomization and colocalization analyses to investigate the associations between mitochondrial-related genes and IBD via integrating multi-omics.

Methods: Summary-level data of mitochondrial gene methylation, expression and protein abundance levels were obtained from corresponding methylation, expression and protein quantitative trait loci studies, respectively.

Resolvin and lipoxin metabolism network regulated by Hyssopus Cuspidatus Boriss extract in asthmatic mice.

Resolvin (Rv) and lipoxin (Lx) play important regulative roles in the development of several inflammation-related diseases. The dysregulation of their metabolic network is believed to be closely related to the occurrence and development of asthma. The Hyssopus Cuspidatus Boriss extract (SXCF) has long been used as a treatment for asthma, while the mechanism of anti-inflammatory and anti-asthma action targeting Rv and Lx has not been thoroughly investigated.

Mediating role of systemic inflammation in the association between heavy metals exposure and periodontitis risk.

Background: This study evaluated the mediating role of systemic inflammation in the association between exposure to heavy metals and periodontitis in a nationwide sample of adults.

Methods: Pooled cross-sectional data from the National Health and Nutrition Examination Survey (NHANES 2009-2014) were used (n = 8993). Periodontitis was defined by a full-mouth examination and classified as no/mild and moderate/severe (mod/sev) groups.

Decreased TMIGD1 aggravates colitis and intestinal barrier dysfunction via the BANF1-NF-κB pathway in Crohn's disease.

Background: Disrupted intestinal epithelial barrier is one of the major causes of Crohn's disease (CD). Novel molecular targets for intestinal epithelial barrier are essential to treatment of CD. Transmembrane and immunoglobulin domain-containing protein 1 (TMIGD1) is an adhesion molecule that regulates cell adhesion, migration, and enterocyte differentiation.

Serum Anti-Aging Protein α-Klotho Mediates the Association between Diet Quality and Kidney Function.

Adherence to healthy dietary patterns is associated with a reduced risk of kidney dysfunction. Nevertheless, the age-related mechanisms that underpin the relationship between diet and kidney function remain undetermined. This study aimed to investigate the mediating role of serum α-Klotho, an anti-aging protein, in the link between a healthy diet and kidney function.