Host Genetics Research Articles

Causal inference can lead us to modifiable mechanisms and informative archetypes in sepsis.

Medical progress is reflected in the advance from broad clinical syndromes to mechanistically coherent diagnoses. By this metric, research in sepsis is far behind other areas of medicine-the word itself conflates multiple different disease mechanisms, whilst excluding noninfectious syndromes (e.g.,trauma, pancreatitis) with similar pathogenesis. New technologies, both for deep phenotyping and data analysis, offer the capability to define biological states with extreme depth. Progress is limited by a fundamental problem: observed groupings of patients lacking shared causal mechanisms are very poor predictors of response to treatment. Here, we discuss concrete steps to identify groups of patients reflecting archetypes of disease with shared underlying mechanisms of pathogenesis. Recent evidence demonstrates the role of causal inference from host genetics and randomised clinical trials to inform stratification analyses. Genetic studies can directly illuminate drug targets, but in addition they create a reservoir of statistical power that can be divided many times among potential patient subgroups to test for mechanistic coherence, accelerating discovery of modifiable mechanisms for testing in trials. Novel approaches, such as subgroup identification in-flight in clinical trials, will improve efficiency. Within the next decade, we expect ongoing large-scale collaborative projects to discover and test therapeutically relevant sepsis archetypes.

The Gut Microbiome Advances Precision Medicine and Diagnostics for Inflammatory Bowel Diseases

The gut microbiome emerges as an integral component of precision medicine because of its signature variability among individuals and its plasticity, which enables personalized therapeutic interventions, especially when integrated with other multiomics data. This promise is further fueled by advances in next-generation sequencing and metabolomics, which allow in-depth high-precision profiling of microbiome communities, their genetic contents, and secreted chemistry. This knowledge has advanced our understanding of our microbial partners, their interaction with cellular targets, and their implication in human conditions such as inflammatory bowel disease (IBD). This explosion of microbiome data inspired the development of next-generation therapeutics for treating IBD that depend on manipulating the gut microbiome by diet modulation or using live products as therapeutics. The current landscape of artificial microbiome therapeutics is not limited to probiotics and fecal transplants but has expanded to include community consortia, engineered probiotics, and defined metabolites, bypassing several limitations that hindered rapid progress in this field such as safety and regulatory issues. More integrated research will reveal new therapeutic targets such as enzymes or receptors mediating interactions between microbiota-secreted molecules that drive or modulate diseases. With the shift toward precision medicine and the enhanced integration of host genetics and polymorphism in treatment regimes, the following key questions emerge: How can we effectively implement microbiomics to further personalize the treatment of diseases like IBD, leveraging proven and validated microbiome links? Can we modulate the microbiome to manage IBD by altering the host immune response? In this review, we discuss recent advances in understanding the mechanism underpinning the role of gut microbes in driving or preventing IBD. We highlight developed targeted approaches to reverse dysbiosis through precision editing of the microbiome. We analyze limitations and opportunities while defining the specific clinical niche for this innovative therapeutic modality for the treatment, prevention, and diagnosis of IBD and its potential implication in precision medicine.

A genome-wide association study of adults with community-acquired pneumonia

BackgroundCommunity-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of infection. Here we aimed to identify genetic risk loci for CAP using a case-control genome-wide association study (GWAS).MethodsWe performed a GWAS on 3,765 Spanish individuals, including 257 adult patients hospitalized with CAP and 3,508 population controls. Pneumococcal CAP was documented in 30% of patients; the remaining 70% were selected among patients with unidentified microbiological etiology. We tested 7,6 million imputed genotypes using logistic regressions. UK Biobank GWAS of bacterial pneumonia were used for results validation. Subsequently, we prioritized genes and likely causal variants based on Bayesian fine mapping and functional evidence. Imputation and association of classical HLA alleles and amino acids were also conducted.ResultsSix independent sentinel variants reached the genome-wide significance (p < 5 × 10-8), three on chromosome 6p21.32, and one for each of the chromosomes 4q28.2, 11p12, and 20q11.22. Only one variant at 6p21.32 was validated in independent GWAS of bacterial and pneumococcal pneumonia. Our analyses prioritized C4orf33 on 4q28.2, TAPBP on 6p21.32, and ZNF341 on 20q11.22. Interestingly, genetic defects of TAPBP and ZNF341 are previously known inborn errors of immunity predisposing to bacterial pneumonia, including pneumococcus and Haemophilus influenzae. Associations were all non-significant for the classical HLA alleles.ConclusionsWe completed a GWAS of CAP and identified four novel risk loci involved in CAP susceptibility.

Dysregulation of T cell response in the pathogenesis of inflammatory bowel disease.

Inflammatory bowel disease (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), are gut inflammatory diseases that were earlier prevalent in the Western Hemisphere but now are on the rise in the East, with India standing second highest in the incidence rate in the world. Inflammation in IBD is a cause of dysregulated immune response, wherein helper T (Th) cell subsets and their cytokines play a major role in the pathogenesis of IBD. In addition, gut microbiota, environmental factors such as dietary factors and host genetics influence the outcome and severity of IBD. Dysregulation between effector and regulatory T cells drives gut inflammation, as effector T cells like Th1, Th17 and Th9 subsets Th cell lineages were found to be increased in IBD patients. In this review, we attempted to discuss the role of different Th cell subsets together with other T cells like CD8+ T cells, NKT and γδT cells in the outcome of gut inflammation in IBD. We also highlighted the potential therapeutic candidates for IBD.

The Impact of Exposure Dosage and Host Genetics on the Shedding Kinetics of Flavobacterium psychrophilum in Rainbow Trout.

Flavobacterium psychrophilum, the causative agent of bacterial cold water disease (BCWD), is one of the leading pathogens in rainbow trout (Oncorhynchus mykiss) aquaculture. To date, there is little knowledge of the transmission kinetics of F. psychrophilum over the course of infection. In particular, how transmission is affected by host genotype and pathogen exposure dosage are not well studied. In order to fill in these knowledge gaps, we exposed two divergently selected lines of rainbow trout (ARS-Fp-R and ARS-Fp-S) to a range of dosages of F. psychrophilum (strain CSF117-10). We then measured mortality and bacterial shedding to estimate transmission risk at multiple time points since initial infection. As dosage increased, the number of fish shedding and the amount of bacteria shed increased ranging from 0% to 100% and 103 to 108 cells fish-1 h-1, respectively. In addition, we found that disease resistance (survival) was not correlated with transmission risk blocking, in that 67% of fish which shed bacteria experienced no clinical disease. In general, fish mortality began on Day 3, peaked between Days 5-7 and was higher in the ARS-Fp-R line. Results from this study could be used to develop epidemiological models and improve disease management, particularly in the context of aquaculture and selective breeding.

The impact of host genetics on microbe assemblages in three types of mrigal carp (Cirrhinus mrigala)

Host–microbiota interactions are molecular and physical interactions between the microbiota and the host that play significant roles in the lifespan of animals. In the present study, two types of gynogenetic mrigal carp (GMCC and GMCW) and the original maternal mrigal carp (MC) were used as a models to investigate host–microbiota interactions. The two types of gynogenetic mrigal carps showed faster growth and better cold tolerance than the MC fish. Compared to those in MC, a large number of goblet cells and higher activity of cellulase and pepsin were detected in the intestine of gynogenetic fish. The composition and abundance of the microbial communities significantly differed among the three types of mrigal carp and water, with Proteobacteria, Firmicutes and Chloroflexi being the most dominant microbes in the GMCC, GMCW and MC fish, respectively. Pseudomonas, Lactococcus and Defluviicoccus were the biomarker genera in the GMCC, GMCW and MC fish. Network analysis revealed no relationships between fish and water, but the dominant genera was positively correlated with the abundance of certain enzymes. Functional analysis revealed the dominant genera associated with amino acid metabolism, fatty acid metabolism and bile acid biosynthesis. Our results suggested that host genetics may affected gut microbe assembly and that the specific metabolic functions of gut microbes may contribute to growth performance through the microbe-gut-liver axis.

Microbial diversity and biogeography across gastrointestinal tracts of Takifugu pufferfish revealed by full-length 16S amplicon sequencing

Fish, which are vital for both aquatic ecosystem functionality and global food supply, rely heavily on their gastrointestinal tract (GIT) microbiota for the digestion that underpins their growth and health. Takifugu pufferfish, which are an example of species evolved through adaptive radiation, possess a GIT that is specialized for antipredator defense and gluttonous feeding behaviors, offering a unique model to explore the effects of GIT compartmentalization and host genetics on gut microbial communities. Here we compiled 78 full and partial-length 16S rRNA amplicon datasets across three anteroposteriorly distinct intestinal sites in a cohort of cohabitating artificial hybrid and purebred Takifugu pufferfishes. Our findings reveal a compositional and functional biogeography of pufferfish gut microbiota along the GIT and between host genetics. Additionally, the differential abundance of specific amplicon sequence variants and their correlation with host genetic backgrounds and intestinal sections highlight the role of environmental filtering in shaping microbial communities, with certain bacterial taxa exhibiting strong preferences for particular intestinal sites or genetic backgrounds, suggesting potential localized adaptation or functional specialization. This study enhances our understanding of the intricate interplay between host genetics, gut anatomy, and microbiota in fish, underscoring the importance of detailed microbial profiling in conservation efforts and aquaculture practices, and emphasizing the necessity of integrating full-length 16S rRNA sequencing with partial-length datasets to comprehensively understand microbial diversity and function, paving the way for improved fish health management and sustainable aquaculture strategies.

Molecular Identification and Genetic Diversity Analysis of Papaya Leaf Curl China Virus Infecting Ageratum conyzoides.

Papaya leaf curl China virus (PaLCuCNV) is a damaging plant pathogen causing substantial losses to crop. The complete genomes of three PaLCuCNV isolates from Ageratum conyzoides were obtained and combined with the 68 reference isolates in GenBank for comprehensive genetic diversity analyses using specialized computational tools. Sequence alignment revealed nucleotide sequence similarity ranging from 85.3% to 99.9% among 71 PaLCuCNV isolates. Employing phylogenetic analysis, 71 PaLCuCNV sequences were clustered into five groups, with no significant correlation observed between genetic differentiation and either host species or geographical origin. Additionally, 13 recombination events across all PaLCuCNV isolates were identified. Genetic diversity analysis indicated the ongoing expansion and evolution of PaLCuCNV populations, supported by a neutral model. Moreover, significant genetic differentiation was observed among distinct viral populations, primarily attributed to genetic drift. Overall, our findings provide valuable insights into the detection, genetic variation, and evolutionary dynamics of PaLCuCNV.

Host genetics shapes Pinus radiata phenotypic plasticity under drought and is linked with root-associated soil microbiome shifts

Under current and future climate scenarios, identifying drought-resistant tree species, tree genotypes, and beneficial interactions between trees and their root-associated soil microbiomes is becoming more imperative for maintaining tree health and sustaining increasingly vulnerable forests. We designed a genotype x soil x watering x time glasshouse experiment using Pinus radiata as a model tree to assess the magnitude of the effect of host genotype and root-associated soil microbiome on the phenotype response (functional traits, metabolome, nutrients) under drought. We identified the shikimate pathway as a critical metabolic pathway for Pinus radiata drought resistance, with the shikimic acid intermediate being one of the strongest drought signals, besides downstream metabolites such as flavonoids and phenylpropanoids. Overall, we found that the host genotype diversity was a key actor in the observed phenotype response of P. radiata to drought. In contrast, the microbiome was attributed a minor supporting role. Contrary to our hypothesis, dry soils could not support drought-sensitive genotypes under drought stress. Instead, the drought-resistant genotype was able to leverage locally adaptive bacteria to match local selective drought pressures at the expense of tree growth. This highlights the significance of finding specific combinations of tree genotype and mutualistic microbial communities that would thrive under future environmental pressures.

Impact of Human Immunological Responses and Viral Genetic Diversity on Outbreak of Human Monkeypox Virus. A Comprehensive Literature Review Study

Monkeypox was caused by Monkeypox Virus (MPXV) and can infect both humans and animals. An understanding of the interplay between host immunity and genetic diversity was necessary to understand the etiology and epidemiology of monkeypox disease. Objective: To clarify how genetic differences and host immune responses interact when a moneypox infection occurs. Furthermore, we also aim to provide insights into individual variability in illness outcomes and possible treatment targets by investigating how distinct genetic profiles affect immune system activation and efficacy. Methods: Recent research on monkeypox, concentrating on the immune response mechanisms of the host and genetic variables linked to virus vulnerability have thoroughly analyzed. For this purpose, the data were searched from various research engines such as google scholar, pubmed, medline etc., by using different key words i.e., monkeypox and host immunity, monkeypox and antibodies interactions, monkeypox outbreak, mnkeypox strains. Conclusions: The way a monkeypox infection progresses and turns out was greatly influenced by the interplay between host genetic differences and immunological responses. Public health initiatives and the creation of tailored treatment plans can both benefit from the identification of genetic markers linked to immunological response profiles and vulnerability.

Idiosyncratic Hepatocellular Drug-Induced Liver Injury by Flucloxacillin with Evidence Based on Roussel Uclaf Causality Assessment Method and HLA B*57:01 Genotype: From Metabolic CYP 3A4/3A7 to Immune Mechanisms.

Idiosyncratic drug-induced liver injury (iDILI) by flucloxacillin presents as both cholestatic and hepatocellular injury. Its mechanistic steps are explored in the present analysis as limited data exist on the cascade of events leading to iDILI in patients with an established diagnosis assessed for causality by the Roussel Uclaf Causality Assessment Method (RUCAM). Studies with human liver microsomes showed that flucloxacillin is a substrate of cytochrome P450 (CYP) with ist preferred isoforms CYP 3A4/3A7 that toxified flucloxacillin toward 5'-hydroxymethylflucloxacillin, which was cytotoxic to human biliary epithelial cell cultures, simulating human cholestatic injury. This provided evidence for a restricted role of the metabolic CYP-dependent hypothesis. In contrast, 5'-hydroxymethylflucloxacillin generated metabolically via CYP 3A4/3A7 was not cytotoxic to human hepatocytes due to missing genetic host features and a lack of non-parenchymal cells, including immune cells, which commonly surround the hepatocytes in the intact liver in abundance. This indicated a mechanistic gap regarding the clinical hepatocellular iDILI, now closed by additional studies and clinical evidence based on HLA B*57:01-positive patients with iDILI by flucloxacillin and a verified diagnosis by the RUCAM. Naïve T-cells from volunteers expressing HLA B*57:01 activated by flucloxacillin when the drug antigen was presented by dendritic cells provided the immunological basis for hepatocellular iDILI caused by flucloxacillin. HLA B*57:01-restricted activation of drug-specific T-cells caused covalent binding of flucloxacillin to albumin acting as a hapten. Following drug stimulation, T-cell clones expressing CCR4 and CCR9 migrated toward CCL17 and CCL25 and secreted interferon-γ and cytokines. In conclusion, cholestatic injury can be explained metabolically, while hepatocellular injury requires both metabolic and immune activation.

GWAS and polygenic risk score of severe COVID-19 in Eastern Europe.

COVID-19 disease has infected more than 772 million people, leading to 7 million deaths. Although the severe course of COVID-19 can be prevented using appropriate treatments, effective interventions require a thorough research of the genetic factors involved in its pathogenesis. We conducted a genome-wide association study (GWAS) on 7,124 individuals (comprising 6,400 controls who had mild to moderate COVID-19 and 724 cases with severe COVID-19). The inclusion criteria were acute respiratory distress syndrome (ARDS), acute respiratory failure (ARF) requiring respiratory support, or CT scans indicative of severe COVID-19 infection without any competing diseases. We also developed a polygenic risk score (PRS) model to identify individuals at high risk. We identified two genome-wide significant loci (P-value <5 × 10-8) and one locus with approximately genome-wide significance (P-value = 5.92 × 10-8-6.15 × 10-8). The most genome-wide significant variants were located in the leucine zipper transcription factor like 1 (LZTFL1) gene, which has been highlighted in several previous GWAS studies. Our PRS model results indicated that individuals in the top 10% group of the PRS had twice the risk of severe course of the disease compared to those at median risk [odds ratio = 2.18 (1.66, 2.86), P-value = 8.9 × 10-9]. We conducted one of the largest studies to date on the genetics of severe COVID-19 in an Eastern European cohort. Our results are consistent with previous research and will guide further epidemiologic studies on host genetics, as well as for the development of targeted treatments.

Missense variant rs75603675 within TMPRSS2 gene is associated with the increased risk of severe form of COVID-19

Host genetics among other factors play an important role in COVID-19 disease severity. TMPRSS2, a serine protease, facilitates the priming of the SARS-CoV-2 spike protein, which is essential for the virus to enter the host cell. Several studies had targeted the TMPRSS2 polymorphisms with respect to SARS-CoV-2 infection and COVID-19 disease severity. Initially, the Whole Exome Sequencing (WES) of 7 healthy individuals and 22 COVID-19 patients with different degrees of disease severity was conducted to find the mutational landscape in different genes. A total of 26 single nucleotide polymorphisms (SNPs) were identified of which six were within the exons of TMPRSS2 (four synonymous and two nonsynonymous variants) while the rest of the 20 SNPs were recognized within the flanking intronic regions of TMPRSS2 gene. The nonsynonymous SNPs, rs75603675 and rs12329760, were further evaluated for association with disease severity in a larger sample size of 120 individuals by PCR followed by Sanger sequencing. Neither allelic nor genotypic distributions of rs12329760 were significantly associated with COVID-19 disease severity. However, individuals harboring the A allele of rs75603675 was found to have higher risk of severe COVID-19 compared to the C allele [OR (95%CI): 1.95 (1.11–3.39), p = 0.019]. Also, the genotype A/A [OR (95%CI): 5.13 (1.00–26.38), p = 0.033] of rs75603675 was associated with increased risk of severe COVID-19 under the recessive genetic inheritance model. Although the impact of COVID-19 pandemic has waned due to vaccination and public health measures, continued research on the association of COVID-19 disease severity and infection susceptibility with host genetics is required to shed valuable insights on the future long-term health effects of COVID-19 and impact of new variants on different populations and enable implication of proper informed healthcare strategies during future public health crises.

The Biology, Impact, and Management of Xyleborus Beetles: A Comprehensive Review.

Xyleborus beetles, a diverse group of ambrosia beetles, present challenges to forestry and agriculture due to their damaging burrowing behavior and symbiotic relationships with fungi. This review synthesizes current knowledge on the biology, ecology, and management of Xyleborus. We explore the beetles' life cycle, reproductive strategies, habitat preferences, and feeding habits, emphasizing their ecological and economic impacts. Control and management strategies, including preventive measures, chemical and biological control, and integrated pest management (IPM), are critically evaluated. Recent advances in molecular genetics and behavioral studies offer insights into genetic diversity, population structure, and host selection mechanisms. Despite progress, managing Xyleborus effectively remains challenging. This review identifies future research needs and highlights innovative control methods, such as biopesticides and pheromone-based trapping systems.

187 Exploring deep shotgun sequencing to understand the rumen microbial function in Angus bulls with divergent RFI EPD

Abstract We investigated the rumen microbiome of Angus bulls selected for Residual Feed Intake-Expected Progeny Difference (RFI-EPD) utilizing deep shotgun metagenomic sequencing. Negative RFI-EPD bulls (NegRFI: n = 10; RFI-EPD = -0.3883 kg/d) and Positive RFI-EPD bulls (PosRFI: n = 10; RFI-EPD = 0.2935 kg/d) were selected from a group of 59 Angus bulls [average body weight (BW) = 427.81 ± 18.77 kg] fed a high-forage total mixed ration after a 59-d testing period. At the end of the 59-d period, rumen fluid samples were collected for bacterial DNA extraction and subsequent shotgun metagenomic sequencing. Results of the metagenome analysis revealed greater gene richness in NegRFI bulls compared with PosRFI. Analysis of similarity revealed a significant difference (P = 0.05) in the rumen microbial community between the NegRFI and PosRFI. Linear Discriminant Analysis effect size (Lefse) was used to identify the differentially abundant taxa. The Lefse results showed that class Fibrobacteria (LDA = 5.1) and genus Fibrobacter (LDA = 4.8) were the most differentially enriched markers in NegRFI bulls, compared with PosRFI bulls. Relative abundance of the carbohydrate-active enzymes was also compared using lefse analysis. The results showed greater relative abundance of glycoside hydrolases and carbohydrate-binding modules such as GH5, CBM86, CBM35, GH43, and CBM6 (LDA &amp;gt; 3.0) in NegRFI bulls whereas GH13 and GT2 were greater in PosRFI. The distinct metabolic and microbial profiles observed in NegRFI, compared with PosRFI bulls, characterized by greater gene richness and specific taxa such as Fibrobacter, and variations in carbohydrate-active enzymes, underscore the potential genetic and functional differences in their rumen microbiome. These findings contribute to a deeper understanding of the interplay between host genetics, microbiota, and feed efficiency in Angus bulls, opening avenues for targeted interventions and advancements in livestock management practices.

Discovery and biological confirmation of a highly divergent Tacaribe virus in metatranscriptomic data from neotropical bats.

Clade B New World arenaviruses (NWA) include rodent-borne lethal hemorrhagic fever viruses, whereas Tacaribe virus (TCRV) stands out because of its detection in bats and its presumably low zoonotic potential. However, the bat association of TCRV was put into question by lethal experimental neotropical fruit bat infections and rare TCRV detection in bats. Scarce genomic data include near-identical viruses from Caribbean bats and ticks from the US sampled 50 years later. The prototype TCRV isolate used for experimental risk assessments has an extensive passage history in suckling mouse brains. Exploring the true genetic diversity, geographic distribution, and host range of bat-borne NWA is pivotal to assess their zoonotic potential and transmission cycles. We analyzed metatranscriptomic data for evidence of NWA identifying a highly divergent TCRV in bats and confirmed virus detection in original biological materials, supporting the association of TCRV with neotropical bats and warranting investigation of strain-associated TCRV pathogenicity.

Sex-specific causal effects of serum sex hormones on COVID-19 susceptibility and severity: Evidence from the UK Biobank and COVID-19 Host Genetics Initiative

BackgroundSeveral hormone therapies, such as androgen receptor signaling inhibition, are being investigated for their potential effectiveness against coronavirus disease 2019 (COVID-19). However, the causal relationships between serum sex hormones and the predisposition to, as well as the severity of, COVID-19, with a particular emphasis on potential gender-specific impacts, remain elusive. MethodsIn this study, using the latest data from the UK Biobank (up to 424,907 individuals) and COVID-19 Host Genetics Initiative (up to 1,878,143 individuals), we conducted a two-sample Mendelian randomization (MR) to systematically assess the sex-specific causal effects of serum sex hormone levels, total testosterone (TT), bioavailable testosterone (BT) in particular, on COVID-19 outcomes. The inverse-variance weighted method was used in the main MR analysis. Furthermore, we additionally performed a series of sensitivity analyses to assess the robustness of MR effect estimates against potential biases caused by invalid genetic variants. ResultsOur MR analysis revealed novel causal associations between bioavailable testosterone and serum estradiol levels, and SARS-CoV-2 infection in women, but not men, except for a suggestive inverse causal association between estradiol levels and COVID-19 severity in men. ConclusionThese novel findings improve our understanding of the sex-specific causal nature of androgen and estrogen in relation to COVID-19 outcomes, and suggest that bioavailable testosterone and estradiol levels may serve as potential therapeutic targets for preventing SARS-CoV-2 infection and improving patient outcomes.

Host genetics and gut microbiota synergistically regulate feed utilization in egg-type chickens

BackgroundFeed efficiency is a crucial economic trait in poultry industry. Both host genetics and gut microbiota influence feed efficiency. However, the associations between gut microbiota and host genetics, as well as their combined contributions to feed efficiency in laying hens during the late laying period, remain largely unclear.MethodsIn total, 686 laying hens were used for whole-genome resequencing and liver transcriptome sequencing. 16S rRNA gene sequencing was conducted on gut chyme (duodenum, jejunum, ileum, and cecum) and fecal samples from 705 individuals. Bioinformatic analysis was performed by integrating the genome, transcriptome, and microbiome to screen for key genetic variations, genes, and gut microbiota associated with feed efficiency.ResultsThe heritability of feed conversion ratio (FCR) and residual feed intake (RFI) was determined to be 0.28 and 0.48, respectively. The ileal and fecal microbiota accounted for 15% and 10% of the FCR variance, while the jejunal, cecal, and fecal microbiota accounted for 20%, 11%, and 10% of the RFI variance. Through SMR analysis based on summary data from liver eQTL mapping and GWAS, we further identified four protein-coding genes, SUCLA2, TNFSF13B, SERTM1, and MARVELD3, that influence feed efficiency in laying hens. The SUCLA2 and TNFSF13B genes were significantly associated with SNP 1:25664581 and SNP rs312433097, respectively. SERTM1 showed significant associations with rs730958360 and 1:33542680 and is a potential causal gene associated with the abundance of Corynebacteriaceae in feces. MARVELD3 was significantly associated with the 1:135348198 and was significantly correlated with the abundance of Enterococcus in ileum. Specifically, a lower abundance of Enterococcus in ileum and a higher abundance of Corynebacteriaceae in feces were associated with better feed efficiency.ConclusionsThis study confirms that both host genetics and gut microbiota can drive variations in feed efficiency. A small portion of the gut microbiota often interacts with host genes, collectively enhancing feed efficiency. Therefore, targeting both the gut microbiota and host genetic variation by supporting more efficient taxa and selective breeding could improve feed efficiency in laying hens during the late laying period.

Epidemiological and genetic aspects of pulmonary tuberculosis in Kazakhstan

ObjectiveTuberculosis is a major health problem in many countries, including Kazakhstan. Host genetics can affect TB risk, and epidemiological and social factors may contribute to disease progression. Due to the high incidence of pulmonary tuberculosis in the country, our research aimed to study the epidemiological and genetic aspects of pulmonary tuberculosis in Kazakhstan. Material and methods1026 participants of Central Asian origin were recruited in the study: 342 individuals diagnosed with active PTB, 342 household contacts, and 342 controls without a family history of TB. Genetic polymorphisms of selected genes were determined by real-time polymerase chain reaction. The association between the risk of pulmonary TB and polymorphisms was evaluated using logistic regression and assessed with the ORs and their corresponding 95 % CIs, and the significance level was determined as p < 0.05. ResultsEpidemiological data revealed that underweight BMI (χ² = 89.97, p < 0.001), employment (χ² = 39.28, p < 0.001), and diabetes (χ² = 12.38, p < 0.001) showed a significant association with PTB. A/T polymorphism of the IFG gene showed a lower risk, and A/A polymorphism showed an increased risk of susceptibility to TB. A/A polymorphism of the IFG gene was associated with an almost 3-fold increased risk of PTB, and A/T polymorphism of the IFG gene was associated with a decreased risk of PTB (OR = 0.67, 95 % CI = 0.49–0.92, p = 0.01). The analysis revealed a decreased risk of PTB for A/A polymorphism of the VDR ApaI (OR = 0.67, 95 % CI = 0.46–0.97, p < 0.05). A/A polymorphism of the TLR8 gene was associated with a 1.5-fold increased risk of PTB (OR = 1.53, 95 % CI = 1.00–2.33, p < 0.05). ConclusionResults showed that gender, employment, underweight BMI and diabetes are associated with PTB incidence in our study cohort. The A/A genotype of the IFG (rs2430561) and an A/A genotype of the TLR8 (rs3764880) genes were associated with an increased risk of PTB. A/T polymorphism of the IFG (rs2430561) and A/A polymorphism of the VDR ApaI were associated with a decreased risk of PTB.

The Role of Host Genetics and Intestinal Microbiota and Metabolome as a New Insight into IBD Pathogenesis.

Inflammatory bowel disease (IBD) is an incurable, chronic disorder of the gastrointestinal tract whose incidence increases every year. Scientific research constantly delivers new information about the disease and its multivariate, complex etiology. Nevertheless, full discovery and understanding of the complete mechanism of IBD pathogenesis still pose a significant challenge to today's science. Recent studies have unanimously confirmed the association of gut microbial dysbiosis with IBD and its contribution to the regulation of the inflammatory process. It transpires that the altered composition of pathogenic and commensal bacteria is not only characteristic of disturbed intestinal homeostasis in IBD, but also of viruses, parasites, and fungi, which are active in the intestine. The crucial function of the microbial metabolome in the human body is altered, which causes a wide range of effects on the host, thus providing a basis for the disease. On the other hand, human genomic and functional research has revealed more loci that play an essential role in gut homeostasis regulation, the immune response, and intestinal epithelial function. This review aims to organize and summarize the currently available knowledge concerning the role and interaction of crucial factors associated with IBD pathogenesis, notably, host genetic composition, intestinal microbiota and metabolome, and immune regulation.