Synergy of gut microbiota and host genome in driving heterosis expression of chickens.

Heterosis has been widely utilized in agricultural production. Despite over a century of extensive research, the underlying mechanisms of heterosis remain elusive. Most hypotheses and research have focused on the genetic basis of heterosis. However, the potential role of gut microbiota in heterosis has been largely ignored. Here, we carefully design a crossbreeding experiment with two distinct broiler breeds and conduct 16S rRNA amplicon and transcriptome sequencing to investigate the synergistic role of gut microbiota and host genes in driving heterosis. We find that the breast muscle weight of the hybrids exhibits a high heterosis, 6.28% higher than mid-parent value. A notable difference is observed in the composition and potential function of cecal microbiota between hybrids and their parents. Over 90% of the differentially colonized microbiota and differentially expressed genes exhibit nonadditive patterns. Integrative analyses uncover associations between nonadditive genes and nonadditive microbiota, including a connection between the expression of cellular signaling pathway and metabolism-related genes and the abundance of Odoribacter, Oscillibacter, and Alistipes in hybrids. Moreover, higher abundances of these microbiota are related to better meat yield. In summary, these findings highlight the importance of gut microbiota in heterosis, serving as crucial factors that modulate heterosis expression in chickens.

Transcriptomic and epigenomic landscapes of muscle growth during the postnatal period of broilers.

BACKGROUND: Broilers stand out as one of the fastest-growing livestock globally, making a substantial contribution to animal meat production. However, the molecular and epigenetic mechanisms underlying the rapid growth and development of broiler chickens are still unclear. This study aims to explore muscle development patterns and regulatory networks during the postnatal rapid growth phase of fast-growing broilers. We measured the growth performance of Cornish (CC) and White Plymouth Rock (RR) over a 42-d period. Pectoral muscle samples from both CC and RR were randomly collected at day 21 after hatching (D21) and D42 for RNA-seq and ATAC-seq library construction. RESULTS: The consistent increase in body weight and pectoral muscle weight across both breeds was observed as they matured, with CC outpacing RR in terms of weight at each stage of development. Differential expression analysis identified 398 and 1,129 genes in the two dimensions of breeds and ages, respectively. A total of 75,149 ATAC-seq peaks were annotated in promoter, exon, intron and intergenic regions, with a higher number of peaks in the promoter and intronic regions. The age-biased genes and breed-biased genes of RNA-seq were combined with the ATAC-seq data for subsequent analysis. The results spotlighted the upregulation of ACTC1 and FDPS at D21, which were primarily associated with muscle structure development by gene cluster enrichment. Additionally, a noteworthy upregulation of MUSTN1, FOS and TGFB3 was spotted in broiler chickens at D42, which were involved in cell differentiation and muscle regeneration after injury, suggesting a regulatory role of muscle growth and repair. CONCLUSIONS: This work provided a regulatory network of postnatal broiler chickens and revealed ACTC1 and MUSTN1 as the key responsible for muscle development and regeneration. Our findings highlight that rapid growth in broiler chickens triggers ongoing muscle damage and subsequent regeneration. These findings provide a foundation for future research to investigate the functional aspects of muscle development.

Distinct patterns of feed intake and their association with growth performance in broilers.

Improving feed utilization is a vital strategy to meet the growing global demand for meat and promote sustainable food production. Over the past few decades, significant improvements in the feed intake (FI) and feed utilization efficiency of broilers have been achieved through advanced breeding procedures, although dynamic changes in FI and their effects on the feed conversion ratio (FCR) have remained unclear. In this study, we measured individual weekly FI and body weight of 274 male broilers to characterize the dynamic FI patterns and investigate their relationship with growth performance. The broilers were from 2 purebred lines and their crossbreed and measurements were collected from 4 to 6 wk of age. Overall, a continuous increase in the weekly FI occurred from 4 to 6 wk of age, whereas the body weight gain (BWG) reached an inflection point in wk 5. The dynamic change in weekly FI was observed to follow 3 distinct FI patterns: pattern 1, a continuous weekly increase in FI; pattern 2, an increase followed by a plateau; pattern 3, an increase followed by a decrease. The prevalence of these patterns was similar in the purebred and crossbred populations: pattern 2 was most frequent, followed by a moderate proportion of pattern 1, and the lowest proportion of pattern 3. Broilers following pattern 1 displayed significantly better growth performance and feed utilization efficiency than those following pattern 3, emphasizing the importance of maintaining good appetite in the last stage of broiler production. In summary, this study has characterized the dynamic patterns of FI and their association with growth performance. Our results offer a new foundation for improving feed utilization efficiency and investigating feeding regulation in broilers.

Transcriptomic and epigenomic insights into pectoral muscle fiber formation at the late embryonic development in pure chicken lines.

Long-term intensive genetic selection has led to significant differences between broiler and layer chickens, which are evident during the embryonic period. Despite this, there is a paucity of research on the genetic regulation of the initial formation of muscle fiber morphology in chick embryos. Embryonic d 17 (E17) is the key time point for myoblast fusion completion and muscle fiber morphology formation in chickens. This study aimed to explore the genetic regulatory mechanisms underlying the early muscle fiber morphology establishment in broiler chickens of Cornish (CC) and White Plymouth Rock (RR) and layer chickens of White Leghorn (WW) at E17 using the transcriptomic and chromatin accessibility sequencing of pectoral major muscles. The results showed that broiler chickens exhibited significant higher embryo weight and pectoral major muscle weight at E17 compared to layer chickens (P = 0.000). A total of 1,278, 1,248, and 892 differentially expressed genes (DEGs) of RNA-seq data were identified between CC vs. WW, RR vs. WW, and CC vs. RR, separately. All DEGs were combined for cluster analysis and they were divided into 6 clusters, including cluster 1 with higher expression in broilers and cluster 6 with higher expression in layers. DEGs in cluster 1 were enriched in terms related to macrophage activation (P = 0.002) and defense response to bacteria (P = 0.002), while DEGs in cluster 6 showed enrichment in protein-DNA complex (P = 0.003) and monooxygenase activity (P = 0.000). ATAC-seq data analysis identified a total of 38,603 peaks, with 13,051 peaks for CC, 18,780 peaks for RR, and 6,772 peaks for WW. Integrative analysis of transcriptomic and chromatin accessibility data revealed GOLM1, ISLR2, and TOPAZ1 were commonly upregulated genes in CC and RR. Furthermore, screening of all upregulated DEGs in cluster 1 from CC and RR identified GOLM1, ISLR2, and HNMT genes associated with neuroimmune functions and MYOM3 linked to muscle morphology development, showing significantly elevated expression in broiler chickens compared to layer chickens. These findings suggest active neural system connectivity during the initial formation of muscle fiber morphology in embryonic period, highlighting the early interaction between muscle fiber formation morphology and the nervous system. This study provides novel insights into late chick embryo development and lays a deeper foundation for further research.

Enzyme-cargo encapsulation peptides bind between tessellating tiles of the bacterial microcompartment shell.

Bacterial microcompartments are prokaryotic organelles comprising encapsulated enzymes within a thin protein shell. They facilitate metabolic processing including propanediol, choline, glycerol, and ethanolamine utilization, and they accelerate carbon fixation in cyanobacteria. Enzymes targeted to the inside of the microcompartment frequently possess a cargo-encapsulation peptide, but the site to which the peptide binds is unclear. We provide evidence that the encapsulation peptides bind to the hydrophobic groove formed between tessellating subunits of the shell proteins. In silico docking studies provide a compelling model of peptide binding to this prominent hydrophobic groove. This result is consistent with the now widely accepted view that the convex side of the shell oligomers faces the lumen of the microcompartment. The binding of the encapsulation peptide to the groove between tessellating shell protein tiles explains why it has been difficult to define the peptide binding site using other methods, provides a mechanism by which encapsulation-peptide bearing enzymes can promote shell assembly, and explains how the presence of cargo affects the size and shape of the bacterial microcompartment. This knowledge may be exploited in engineering microcompartments or disease prevention by hampering cargo encapsulation.

T7 peptide-mediated co-delivery platform overcoming multidrug-resistant breast cancer: In vitro and in vivo evaluation.

P-glycoprotein (P-gp) overexpressed mutidrug resistance (MDR) is currently a key factor limiting the effectiveness of breast cancer chemotherapy. Systemic administration based on P-gp-associated mechanism leads to severe toxic side effects. Here, we designed a T7 peptide-modified mixed liposome (T7-MLP@DTX/SchB) that, by active targeting co-delivering chemotherapeutic agents and P-gp inhibitors, harnessed synergistic effects to improve the treatment of MDR breast cancer. This study established drug-resistant cell models and animal models. Subsequently, comprehensive evaluations involving cell uptake, cell apoptosis, cellular toxicity assays, in vivo tumor-targeting capability, and anti-tumor activity assays were conducted to assess the drug resistance reversal effects of T7-MLP@DTX/SchB. Additionally, a systematic assessment of the biosafety profile of T7-MLP@DTX/SchB was executed, including blood profiles, biochemical markers, and histopathological examination. It was found that this co-delivery strategy successfully exerted the synergistic effects, since there was a significant tumor growth inhibitory effect on multidrug-resistant breast cancer. Targeted modification with T7 peptide enhanced the therapeutic efficacy remarkably, while vastly ameliorating the biocompatibility compared to free drugs. The intriguing results supported the promising potential use of T7-MLP@DTX/SchB in overcoming MDR breast cancer treatment.

Effect of ethylene production by four pathogenic fungi on the postharvest diseases of green pepper (Capsicum annuum L.).

Ethylene produced by plants generally induces ripening and promotes decay, whereas the effect of ethylene produced by pathogens on plant diseases remains unclear. In this study, four ethylene-producing fungi including Alternaria alternata (A. alternata, Aa), Fusarium verticilliodes (F. verticillioides, Fv), Fusarium fujikuroi 1 (F. fujikuroi 1, Ff-1) and Fusarium fujikuroi 2 (F. fujikuroi 2, Ff-2) were severally inoculated in potato dextrose broth (PDB) media and postharvest green peppers, the ethylene production rates, disease indexes and chlorophyll fluorescence parameters were determined. The results showed that Ff-2 and Fv in the PDB media had the highest and almost the same ethylene production rates. After inoculation with green peppers, Ff-2 treated group still exhibited the highest ethylene production rate, whereas Aa treated group had a weak promotion effect on ethylene production. Moreover, the ethylene production rate of green peppers with mechanical injury was twice that without mechanical injury, and the ethylene production rates of green peppers treated with Aa, Ff-1, Ff-2 and Fv were 1.2, 2.6, 3.8 and 2.8 folds than those of green peppers without treatment, respectively. These results indicated that pathogen infection stimulated the synthesis of ethylene in green peppers. Correlation analysis indicated that the degreening of Fusarium-infected green pepper was significantly positively correlated with the ethylene production rate of green pepper, whereas the disease spot of Aa-infected green pepper had a significant positive correlations with the ethylene production rate of green peppers. Chlorophyll fluorescence results showed that the green peppers already suffered from severe disease after being infected with fungi for 4 days, and Fusarium infection caused early and serious stress, while the harm caused by A. alternata was relatively mild at the early stage. Our results clearly showed that α-keto-γ-methylthiobutyric acid (KMBA)-mediated ethylene synthesis was the major ethylene synthesis pathway in the four postharvest pathogenic fungi. All the results obtained suggested that ethylene might be the main infection factor of Fusarium spp. in green peppers. For pathogenic fungi, stimulating green peppers to produce high level of ethylene played a key role in the degreening of green peppers.

Non-peptidic inhibitors targeting SARS-CoV-2 main protease: A review.

The COVID-19 pandemic continues to pose a threat to global health, and sounds the alarm for research & development of effective anti-coronavirus drugs, which are crucial for the patients and urgently needed for the current epidemic and future crisis. The main protease (Mpro) stands as an essential enzyme in the maturation process of SARS-CoV-2, playing an irreplaceable role in regulating viral RNA replication and transcription. It has emerged as an ideal target for developing antiviral agents against SARS-CoV-2 due to its high conservation and the absence of homologous proteases in the human body. Among the SARS-CoV-2 Mpro inhibitors, non-peptidic compounds hold promising prospects owing to their excellent antiviral activity and improved metabolic stability. In this review, we offer an overview of research progress concerning non-peptidic SARS-CoV-2 Mpro inhibitors since 2020. The efforts delved into molecular structures, structure-activity relationships (SARs), biological activity, and binding modes of these inhibitors with Mpro. This review aims to provide valuable clues and insights for the development of anti-SARS-CoV-2 agents as well as broad-spectrum coronavirus Mpro inhibitors.

High-Performance Ammonia Electrosynthesis from Nitrate in a NaOH-KOH-H2O Ternary Electrolyte.

A glut of dinitrogen-derived ammonia (NH3) over the past century has resulted in a heavily imbalanced nitrogen cycle and consequently, the large-scale accumulation of reactive nitrogen such as nitrates in our ecosystems has led to detrimental environmental issues. Electrocatalytic upcycling of waste nitrogen back into NH3 holds promise in mitigating these environmental impacts and reducing reliance on the energy-intensive Haber-Bosch process. Herein, we report a high-performance electrolyzer using an ultrahigh alkalinity electrolyte, NaOH-KOH-H2O, for low-cost NH3 electrosynthesis. At 3,000 mA/cm2, the device with a Fe-Cu-Ni ternary catalyst achieves an unprecedented faradaic efficiency (FE) of 92.5±1.5 % under a low cell voltage of 3.83 V; whereas at 1,000 mA/cm2, an FE of 96.5±4.8 % under a cell voltage of only 2.40 V was achieved. Techno-economic analysis revealed that our device cuts the levelized cost of ammonia electrosynthesis by ~40 % ($30.68 for Fe-Cu-Ni vs. $48.53 for Ni foam per kmol-NH3). The NaOH-KOH-H2O electrolyte together with the Fe-Cu-Ni ternary catalyst can enable the high-throughput nitrate-to-ammonia applications for affordable and scalable real-world wastewater treatments.

MyoV: a deep learning-based tool for the automated quantification of muscle fibers.

Accurate approaches for quantifying muscle fibers are essential in biomedical research and meat production. In this study, we address the limitations of existing approaches for hematoxylin and eosin-stained muscle fibers by manually and semiautomatically labeling over 660 000 muscle fibers to create a large dataset. Subsequently, an automated image segmentation and quantification tool named MyoV is designed using mask regions with convolutional neural networks and a residual network and feature pyramid network as the backbone network. This design enables the tool to allow muscle fiber processing with different sizes and ages. MyoV, which achieves impressive detection rates of 0.93-0.96 and precision levels of 0.91-0.97, exhibits a superior performance in quantification, surpassing both manual methods and commonly employed algorithms and software, particularly for whole slide images (WSIs). Moreover, MyoV is proven as a powerful and suitable tool for various species with different muscle development, including mice, which are a crucial model for muscle disease diagnosis, and agricultural animals, which are a significant meat source for humans. Finally, we integrate this tool into visualization software with functions, such as segmentation, area determination and automatic labeling, allowing seamless processing for over 400 000 muscle fibers within a WSI, eliminating the model adjustment and providing researchers with an easy-to-use visual interface to browse functional options and realize muscle fiber quantification from WSIs.

Emerging perspectives in the gut-muscle axis: The gut microbiota and its metabolites as important modulators of meat quality.

Animal breeding has made great genetic progress in increasing carcass weight and meat yield in recent decades. However, these improvements have come at the expense of meat quality. As the demand for meat quantity continues to rise, the meat industry faces the great challenge of maintaining and even increasing product quality. Recent research, including traditional statistical analyses and gut microbiota regulation research, has demonstrated that the gut microbiome exerts a considerable effect on meat quality, which has become increasingly intriguing in farm animals. Microbial metabolites play crucial roles as substrates or signalling factors to distant organs, influencing meat quality either beneficially or detrimentally. Interventions targeting the gut microbiota exhibit excellent potential as natural ways to foster the conversion of myofibres and promote intramuscular fat deposition. Here, we highlight the emerging roles of the gut microbiota in various dimensions of meat quality. We focus particularly on the effects of the gut microbiota and gut-derived molecules on muscle fibre metabolism and intramuscular fat deposition and attempt to summarize the potential underlying mechanisms.

Natural variation in OsSEC13 HOMOLOG 1 modulates redox homeostasis to confer cold tolerance in rice.

Rice (Oryza sativa L.) is a cold-sensitive species that often faces cold stress, which adversely affects yield productivity and quality. However, the genetic basis for low-temperature adaptation in rice remains unclear. Here, we demonstrate that 2 functional polymorphisms in O. sativa SEC13 Homolog 1 (OsSEH1), encoding a WD40-repeat nucleoporin, between the 2 subspecies O. sativa japonica and O. sativa indica rice, may have facilitated cold adaptation in japonica rice. We show that OsSEH1 of the japonica variety expressed in OsSEH1MSD plants (transgenic line overexpressing the OsSEH1 allele from Mangshuidao [MSD], cold-tolerant landrace) has a higher affinity for O. sativa metallothionein 2b (OsMT2b) than that of OsSEH1 of indica. This high affinity of OsSEH1MSD for OsMT2b results in inhibition of OsMT2b degradation, with decreased accumulation of reactive oxygen species and increased cold tolerance. Transcriptome analysis indicates that OsSEH1 positively regulates the expression of the genes encoding dehydration-responsive element-binding transcription factors, i.e. OsDREB1 genes, and induces the expression of multiple cold-regulated genes to enhance cold tolerance. Our findings highlight a breeding resource for improving cold tolerance in rice.

Circular RNA-AnnexinA7 accelerates cisplatin resistance in non-small cell lung cancer via modulating microRNA-545-3p to mediate Cyclin D1.

OBJECTIVE: To explore the mechanism of circular RNA (circRNA)-AnnexinA7 (ANXA7) in non-small cell lung cancer (NSCLC) cisplatin (DDP) resistance through microRNA (miR)-545-3p to target Cyclin D1 (CCND1). METHODS: DDP-resistant and non-resistant NSCLC tissues and normal tissues were collected. DDP-resistant cells (A549/DDP and H460/DDP) were constructed. circ-ANXA7, miR-545-3p, CCND1, P-Glycoprotein, and glutathione S-transferase-π in tissues and cells were measured. Analysis of circ-ANXA7 ring structure was performed, as well as detection of circ-ANXA7 distribution in cells. Cell proliferation was detected by MTT and colony formation assay, apoptosis rate was detected by flow cytometry, and cell migration and invasion were evaluated by Transwell assay. The targeting relationship between circ-ANXA7, miR-545-3p and CCND1 was verified. Measurement of tumor volume and quality in mice was performed. RESULTS: Circ-ANXA7 and CCND1 were elevated, while miR-545-3p was suppressed in DDP-resistant NSCLC tissues and cells. Circ-ANXA7 combined with miR-545-3p, which targeted CCND1 to expedite A549/DDP cell proliferation, migration, invasion, DDP resistance, but inhibited cell apoptosis. CONCLUSION: Circ-ANXA7 enhances DDP resistance in NSCLC via absorbing miR-545-3p to target CCND1 and might be a latent therapeutic target for NSCLC.

Quinolines and isoquinolines as HIV-1 inhibitors: Chemical structures, action targets, and biological activities.

Human immunodeficiency virus type 1 (HIV-1), a lentivirus that causes acquired immunodeficiency syndrome (AIDS), poses a serious threat to global public health. Since the advent of the first drug zidovudine, a number of anti-HIV agents acting on different targets have been approved to combat HIV/AIDS. Among the abundant heterocyclic families, quinoline and isoquinoline moieties are recognized as promising scaffolds for HIV inhibition. This review intends to highlight the advances in diverse chemical structures and abundant biological activity of quinolines and isoquinolines as anti-HIV agents acting on different targets, which aims to provide useful references and inspirations to design and develop novel HIV inhibitors for medicinal chemists.

The cecal ecosystem is a great contributor to intramuscular fat deposition in broilers.

Intramuscular fat (IMF) content is a meat quality trait of major economic importance in animal production. Emerging evidence has demonstrated that meat quality can be improved by regulating the gut microbiota. However, the organization and ecological properties of the gut microbiota and its relationship with the IMF content remain unclear in chickens. Here, we investigated the microbial communities of 206 cecal samples from broilers with excellent meat quality. We noted that the cecal microbial ecosystem obtained from hosts reared under the same management and dietary conditions showed clear compositional stratification. Two enterotypes, in which the ecological properties, including diversity and interaction strengths, were significantly different, described the microbial composition pattern. Compared with enterotype 2, enterotype 1, distinguished by the Clostridia_vadinBB60_group, had a higher fat deposition, although no discrepancy was found in growth performance and meat yield. A moderate correlation was observed in the IMF content between 2 muscle tissues, despite the IMF content of thigh muscle was 42.76% greater than that of breast muscle. Additionally, the lower abundance of cecal vadinBE97 was related to higher IMF levels in both muscle tissues. Although vadinBE97 accounted for 0.40% of the total abundance of genera in the cecum, it exhibited significant and positive correlations with other genera (accounting for 25.3% of the tested genera). Our results highlight important insights into the cecal microbial ecosystem and its association with meat quality. Microbial interactions should be carefully considered when developing approaches to improve the IMF content by regulating the gut microbiota in broilers.

Temperature-induced embryonic diapause in chickens is mediated by PKC-NF-κB-IRF1 signaling.

BACKGROUND: Embryonic diapause (dormancy) is a state of temporary arrest of embryonic development that is triggered by unfavorable conditions and serves as an evolutionary strategy to ensure reproductive survival. Unlike maternally-controlled embryonic diapause in mammals, chicken embryonic diapause is critically dependent on the environmental temperature. However, the molecular control of diapause in avian species remains largely uncharacterized. In this study, we evaluated the dynamic transcriptomic and phosphoproteomic profiles of chicken embryos in pre-diapause, diapause, and reactivated states. RESULTS: Our data demonstrated a characteristic gene expression pattern in effects on cell survival-associated and stress response signaling pathways. Unlike mammalian diapause, mTOR signaling is not responsible for chicken diapause. However, cold stress responsive genes, such as IRF1, were identified as key regulators of diapause. Further in vitro investigation showed that cold stress-induced transcription of IRF1 was dependent on the PKC-NF-κB signaling pathway, providing a mechanism for proliferation arrest during diapause. Consistently, in vivo overexpression of IRF1 in diapause embryos blocked reactivation after restoration of developmental temperatures. CONCLUSIONS: We concluded that embryonic diapause in chicken is characterized by proliferation arrest, which is the same with other spices. However, chicken embryonic diapause is strictly correlated with the cold stress signal and mediated by PKC-NF-κB-IRF1 signaling, which distinguish chicken diapause from the mTOR based diapause in mammals.

E3 ligase ligand optimization of Clinical PROTACs.

Proteolysis targeting chimeras (PROTACs) technology can realize the development of drugs for non-druggable targets that are difficult to achieve with traditional small molecules, and therefore has attracted extensive attention from both academia and industry. Up to now, there are more than 600 known E3 ubiquitin ligases with different structures and functions, but only a few have developed corresponding E3 ubiquitin ligase ligands, and the ligands used to design PROTAC molecules are limited to a few types such as VHL (Von-Hippel-Lindau), CRBN (Cereblon), MDM2 (Mouse Doubleminute 2 homolog), IAP (Inhibitor of apoptosis proteins), etc. Most of the PROTAC molecules that have entered clinical trials were developed based on CRBN ligands, and only DT2216 was based on VHL ligand. Obviously, the structural optimization of E3 ubiquitin ligase ligands plays an instrumental role in PROTAC technology from bench to bedside. In this review, we review the structure optimization process of E3 ubiquitin ligase ligands currently entering clinical trials on PROTAC molecules, summarize some characteristics of these ligands in terms of druggability, and provide some preliminary insights into their structural optimization. We hope that this review will help medicinal chemists to develop more druggable molecules into clinical studies and to realize the greater therapeutic potential of PROTAC technology.

Iridium-Catalyzed Intramolecular Asymmetric Allylation of Vinyl Benzoxazinones for the Synthesis of Chiral 4H-3,1-Benzoxazines via Kinetic Resolution.

Chiral benzoxazinones and 4H-3,1-benzoxazines as important motifs are widely found in abundant pharmaceuticals and biological molecules. We herein successfully developed the first kinetic resolution (KR) process of racemic benzoxazinones through Ir-catalyzed asymmetric intramolecular allylation, furnishing a wide range of chiral benzoxazinones and 4H-3,1-benzoxazines with excellent results via outstanding KR performances (with the s factor up to 170). This protocol exhibited broad substrate scope generality and good functional group tolerance, and the chiral 4H-3,1-benzoxazine products could be readily transformed to other useful optically active heterocycles.

Genetic and microbiome analysis of feed efficiency in laying hens.

Improving feed efficiency is an important target for poultry breeding. Feed efficiency is affected by host genetics and the gut microbiota, but many of the mechanisms remain elusive in laying hens, especially in the late laying period. In this study, we measured feed intake, body weight, and egg mass of 714 hens from a pedigreed line from 69 to 72 wk of age and calculated the residual feed intake (RFI) and feed conversion ratio (FCR). In addition, fecal samples were also collected for 16S ribosomal RNA gene sequencing (V4 region). Genetic analysis was then conducted in DMU packages by using AI-REML with animal model. Moderate heritability estimates for FCR (h2 = 0.31) and RFI (h2 = 0.52) were observed, suggesting that proper selection programs can directly improve feed efficiency. Genetically, RFI was less correlated with body weight and egg mass than that of FCR. The phenotypic variance explained by gut microbial variance is defined as the microbiability (m2). The microbiability estimates for FCR (m2 = 0.03) and RFI (m2 = 0.16) suggested the gut microbiota was also involved in the regulation of feed efficiency. In addition, our results showed that the effect of host genetics on fecal microbiota was minor in three aspects: 1) microbial diversity indexes had low heritability estimates, and genera with heritability estimates more than 0.1 accounted for only 1.07% of the tested fecal microbiota; 2) the genetic relationship correlations between host genetics and different microbial distance were very weak, ranging from -0.0057 to -0.0003; 3) the microbial distance between different kinships showed no significant difference. Since the RFI has the highest microbiability, we further screened out three genera, including Anaerosporobacter, Candidatus Stoquefichus, and Fournierella, which were negatively correlated with RFI and played positive roles in improving the feed efficiency. These findings contribute to a great understanding of the genetic background and microbial influences on feed efficiency.