An international high impact journal exploring the underlying science behind the function, interactions and design of biomaterials rsc.li/biomaterials-scienceThe Royal Society of Chemistry is the world's leading chemistry community.Through our high impact journals and publications we connect the world with the chemical sciences and invest the profits back into the chemistry community.
Objcctive To observe the curative effects of 1,6-fructose diphosphatc(FDP) on acute heart failure caused by ischemic cardiomyopathy(ICM).Methods Seventy-eight patients with ICM were divided into two groups ,i.e.the control group,in which 41 patiwnts were conventionally treated ,and FDP group,in which 37 patients were treated by conventional method and 1,6FDP(5g,i.v.b.i.d., 10 days). The changes in cardiac function were observed.The cardiac function and changes in the left ventricular morphology were investigated with ultrasonography before and after treatment lasting 10 days.Results The total rate of significant improvcment of heart function in the treatment group( 92%,34/37) was significantly higher than that in the control group (73% ,30/41). After 10 days treatment,the left ventricular ejection fraction,cardiac index,stroke volume,left ventricular end-systolic dimension were significantly improved in the treatment group as compared with the control group.Conclusion The curative effects of 1,6-FDP on hcart failure caused by ischemic cardiomyopathy is good.
Increasing studies show that gut microbiota play a central role in immunity, although the impact of the microbiota on mediation of thymic T cells throughout life is not well understood. Chickens have been shown to be a valuable model for studying basic immunology. Here, we show that changes in the gut microbiota are associated with the development of thymic T cells in young chickens. Our results showed that T-cell numbers in newborn chicks sharply increased from day 0 and peaked at day 49. Interestingly, the α-diversity score pattern of change in gut microbiota also increased after day 0 and continued to increase until day 49. We found that early antibiotic treatment resulted in a dramatic reduction in gut alpha diversity: principal component analysis (PCA) showed that antibiotic treatment resulted in a different cluster from the controls on days 9 and 49. In the antibiotic-treated chickens, we identified eight significantly different ( p < 0.05) microbes at the phylum level and 14 significantly different ( p < 0.05) microbes at the genus level, compared with the controls. Importantly, we found that antibiotic treatment led to a decreased percentage and number of T cells in the thymus when measured at days 9 and 49, as evaluated by flow cytometry. Collectively, our data suggest that intestinal microbiota may be involved in the regulation of T cells in birds, presenting the possibility that interventions that actively modify the gut microbiota in early life may accelerate the maturation of humoral immunity, with resulting anti-inflammatory effects against different pathogens.
Butyric acid is a beneficial feed additive used in animal production, including poultry production. However, there are few reports on butyric acid as a prophylactic treatment against intestinal inflammation in broilers. The current study explored the effect of sodium butyrate (SB) as a prophylactic treatment on the intestinal health and gut microbiota of broilers with intestinal inflammation induced by dextran sulfate sodium (DSS) by monitoring changes in intestinal histopathology, gut leakiness indicators, inflammatory cytokines, and gut microbiota composition. Sodium butyrate supplementation prior to DSS administration significantly reduced the lesion scores of intestinal bleeding (P < 0.05) and increased villus height and the total mucosa of the ileum (P < 0.05). Regardless of intestinal inflammation, supplementation with SB at 300 mg/kg significantly decreased the levels of D (-)-lactate (P < 0.05), interleukin-6, and interleukin-1β (P < 0.05) but increased the level of interleukin-10 (P < 0.05). The SB treatment did not affect the alpha diversity of intestinal microbiota during intestinal inflammation progression but altered their composition, and the microbial community structure of treated broilers was similar to that of control broilers. Taken together, our results reveal the importance of SB in improving intestinal development, inducing an anti-inflammatory effect during intestinal inflammation progression, and modulating the microbial community in broilers. Sodium butyrate seems to be optimized for anti-inflammatory effects at higher doses (300 mg/kg SB).
Nucleotide-binding (NB) leucine-rich repeat (LRR) receptors (NLRs) provide resistance against several plant pathogens. We previously cloned the wheat powdery mildew resistance gene Pm21, which encodes a coiled-coil (CC) NLR that confers broad-spectrum resistance against Blumeria graminis f. sp. tritici. Here, we report comprehensive biochemical and functional analyses of Pm21 CC domain in Nicotiana benthamiana. Transient overexpression assay suggested that only the extended CC (eCC, amino acid residues 1-159) domain has cell-death-inducing activity, whereas the CC-containing truncations, including CC-NB and CC-NB-LRR, do not induce cell-death responses. Coimmunoprecipitation (Co-IP) assay showed that the eCC domain self-associates and interacts with the NB and LRR domains in planta. These results imply that the activity of the eCC domain is inhibited by the intramolecular interactions of different domains in the absence of pathogens. We found that the LRR domain plays a crucial role in D491V-mediated full-length (FL) Pm21 autoactivation. Some mutations in the CC domain leading to the loss of Pm21 resistance to powdery mildew impaired the CC activity of cell-death induction. Two mutations (R73Q and E80K) interfered with D491V-mediated Pm21 autoactivation without affecting the cell-death-inducing activity of the eCC domain. Notably, some susceptible mutants harbouring mutations in the CC domain still exhibited cell-death-inducing activity. Taken together, these results implicate the CC domain of Pm21 in cell-death signalling and disease-resistance signalling, which are potentially independent of each other.
Intestinal microbiota is a critical determinant of growth and risk of metabolic diseases. Our previous studies showed that the locus rs16775833 within the DMRT1 gene is significantly associated with variation in the population structure of the gut microbiota, which is involved in determining the BW of the chicken. To assess the accuracy of correlation of rs16775833 located in the DMRT1 gene on microbial population and BW in birds, 2 genotypes GG and TT in the rs16775833 were identified in Chinese Yellow broiler breeders. We found that BW in the TT genotype group was significantly higher than in the GG genotype group at 7 and 13 wk of age in 777 female chickens. A full-length 16S rRNA sequencing approach was used to further evaluate the fecal bacterial composition of female broilers in 11 TT genotype chickens with high weight (HW-TT) and 11 GG genotype chickens with low weight (LW-GG) at 91 D of age. Partial least squares discriminant analysis revealed that the microbiota of the HW-TT and LW-GG females were clearly separated into 2 clusters. Furthermore, we identified 13 significantly different (P < 0.05) microbes at the genus level and 17 significantly different (P < 0.05) species between the HW-TT and LW-GG groups. Our data show that rs16775833 can modulate the microbial community structure and is associated with the BW of birds. To our knowledge, this is the first time that DMRT1 has been identified as a specific host factor, which is not only involved in sex determination but also has an effect on microbial function that might regulate animal growth.
To study the association in moderate and severe pediatric traumatic brain injury (TBI) between hyperglycemia, hyperlactatemia, acidosis and unfavorable outcome, as assessed by Pediatric Cerebral Performance Category (PCPC) on discharge from the pediatric intensive care unit (PICU).Children <16 years old with TBI and Glasgow Coma Scale (GCS) ≤13 in an Asian multi-center PICU TBI cohort from January 2014 to October 2017 were included in this study. We defined unfavorable outcome as PCPC ≥3-moderate disability, severe disability, vegetative state, and death. We performed logistic regression to investigate the association between metabolic changes with unfavorable outcome. We divided hyperglycemia (glucose >11.1 mmol/L) during PICU admission into early-onset (within 24 h), late-onset (beyond 48 h) and persistent (throughout first 72 h).Among the 305 children analyzed, 136 (44.6%) had unfavorable outcome. Children with unfavorable outcome were more likely to have early hyperglycemia (75/136, 55.1% vs. 33/169, 19.5%; P<0.001), high lactate levels >2.0 mmol/L (74/136, 54.4% vs. 56/169, 32.5%; P<0.001) and initial acidosis (85/136, 62.5% vs. 78/169, 56.1%; P=0.003) compared to those with favorable outcome. After adjusting for gender, GCS ≤8 and presence of polytrauma, early hyperglycemia [adjusted odds ratio (aOR) =3.68, 95% CI: 2.12-6.39, P<0.001] and late hyperglycemia (aOR =13.30, 95% CI: 1.64-107.8, P=0.015] were independently associated with unfavorable outcome. All children with persistent hyperglycemia died.We described unfavorable outcome in pediatric TBI especially with persistent hyperglycemia. Future trials should investigate the causal relationship between glycemic trends, early intervention and outcome in this cohort.
This study explores the role of IgA-coated bacteria in improving feed efficiency in chickens, offering a novel perspective for probiotic screening. Chickens with high feed efficiency were found to have a greater abundance of Gram-positive bacteria, while low feed efficiency chickens exhibited higher levels of Gram-negative bacteria and potential pathogens. Through fecal microbiota transplantation (FMT) and integrating analysis of cecal and IgA-coated microbiota, we precisely identified Blautia as a key genus linked to improved feed efficiency. Further validation demonstrated that Blautia coccoides, a representative species of this genus, enhances feed efficiency and activates B cells to produce Immunoglobulin A (IgA), both in vivo and in vitro. Our findings provide new insights into the potential of IgA-coated bacteria as functional probiotics, offering a promising strategy for enhancing feed efficiency in animal production. The Yellow-feathered broiler is a local poultry breed with independent intellectual property rights in China. The Lingnan Yellow chicken series, developed by our research team, has achieved an annual distribution of over 6 million sets of parent-generation breeding stock. This accounts for approximately 15% of the national market share. Feed efficiency is an essential trait in the livestock and poultry industries, as feed represents between 50% and 70% of total production costs [1, 2]. Therefore, improving feed efficiency is crucial for increasing profitability and ensuring the sustainability of chicken production. It has been reported that symbiotic bacteria in the intestine play a significant role in nutrient digestion and absorption, profoundly influencing feed efficiency [2-4]. However, whether restructuring microbiota can improve feed efficiency and which specific beneficial microbes are responsible for this benefit remains unclear. Immunoglobulin A (IgA) is the most abundant antibody and plays a crucial role in microbial colonization and maintaining intestinal homeostasis [5, 6]. The secretory IgA at mucosal surfaces can directly bind to commensal bacteria, promoting their colonization and coating pathogens to facilitate their removal from the gut [7-9]. Commensal targeting by IgA shapes gut microbiota composition, regulates bacterial behaviors, modulates host physiology, and maintains metabolic homeostasis in both mice and humans [10, 11]. Recent studies have indicated that IgA-targeted bacteria are altered in undernourished mice and children, and these IgA-coated bacteria have a significant impact on nutrient utilization [12, 13]. Thus, investigating IgA-coated bacteria provides a valuable perspective for understanding the role of gut microbiota in improving feed efficiency. Over the last decade, we successfully established two distinct chicken lines with high and low feed efficiency through 15 generations of selective breeding. These lines provide unique resources for investigating the impacts of gut microbiota on feed efficiency. Here, we conducted a comprehensive comparison of the composition and development of cecal and IgA-coated microbiota between two chicken lines. Fecal microbiota transplantation (FMT) was performed to evaluate the role of gut microbiota in feed efficiency. Additionally, integrated analyses of cecal and IgA-coated microbiota enabled precise identification of Blautia as a key biomarker associated with feed efficiency. Its role in improving feed efficiency was further validated through gavage experiments in chickens and mice, complemented by in vitro studies elucidating potential underlying mechanisms. Our research provides valuable insights for identifying potential probiotics to enhance feed efficiency, particularly from the perspective of IgA-coated bacteria. The feed conversion ratio (FCR) is a widely used measure of feed efficiency. Low-FCR animals consume less feed per unit of body weight and are considered efficient, while high-FCR animals are deemed inefficient [14]. After 15 generations of selective breeding, low-feed efficiency (L-FE) chickens exhibited significantly higher FCR and average daily feed intake (ADFI) compared to high-feed efficiency (H-FE) chickens (p < 0.001, Figure1A,B). We performed 16S rRNA sequencing of cecal content at various time points. Across the five time points, L-FE and H-FE chickens shared 284 and 233 common operational taxonomic units (OTUs), respectively (Figure S1A,B). The shared number of OTUs between the two chicken lines increased with age (Figure S1C). Similarly, α-diversity increased with age from Day 1 to 49. From Day 49 onward, the Chao index and observed species remained relatively stable. Interestingly, the microbiota of L-FE chickens showed significantly higher observed species and Chao index on Day 1 (Figure S1D, E), as well as higher Shannon diversity on Day 9 (Figure 1C) compared to H-FE chickens. In contrast, the Shannon diversity in H-FE chickens was significantly higher than in L-FE chickens on Days 49 and 70 (Figure 1C). Microbial composition was shaped by age and exhibited significant differences between the two chicken lines (Figure S1F,G and Table S1). Firmicutes was the dominant phylum at Days 1 and 9, while the relative abundance of Bacteroidetes was increased and became the dominant phyla from Days 49 to 140 (Figure S1F and Tables S2, 3). Notably, on Day 1, the relative abundances of Proteobacteria, major phylum of Gram-negative bacteria that includes a wide variety of pathogenic genera [15], were significantly higher in L-FE chickens compared to H-FE chickens (4.2% vs. 0.0059%, p = 0.0001; Table S1). Microbial phenotype prediction using BugBase revealed that L-FE chickens had a significantly higher relative abundance of Gram-negative bacteria and potential pathogens. In contrast, H-FE chickens exhibited elevated levels of Gram-positive bacteria and enhanced stress tolerance, accompanied by reduced levels of Gram-negative bacteria and potential pathogens (Figure 1D). Consistently, microbial functions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUSt) revealed that the relative abundance of bacteria associated with lipopolysaccharide (LPS) biosynthesis, a component of the outer membrane in most Gram-negative bacteria and a known trigger of inflammatory responses in the host [16], was significantly higher in L-FE chickens compared to H-FE chickens (Figure S2). The elevated levels of Gram-negative bacteria and LPS biosynthesis-associated bacteria observed in L-FE chickens suggest a potential dysbiosis in their gut microbiota [17]. Furthermore, we measured IgA-coated microbiota using IgA-sequencing (IgA-SEQ) in two chicken lines. The α-diversity of IgA-positive bacteria increased with age, and H-FE chickens displayed a significantly higher number of observed species within the IgA-coated microbiota on Day 140 (Figure S3A). Overall, the two chicken lines revealed distinct patterns of IgA-targeted bacteria, as evidenced by significant separation in principal component analysis (PCA) (Figure S3B). Notably, the IgA-targeted bacteria was not solely dependent on their relative abundance within the cecal microbiota. For example, Firmicutes emerged as the predominant phylum within the IgA-coated microbiota at 49 days, whereas Bacteroidetes dominated the cecal microbiome at the same time point (Figure S3C). Additionally, the cecal microbiota of L-FE chickens revealed a higher relative abundance of potential pathogens; however, this was not reflected in the IgA-coated microbiota on Days 49 and 70. Conversely, on Day 140, IgA-coated potential pathogens were significantly more abundant in H-FE chickens compared to L-FE chickens, despite no significant differences in the cecal microbiota (Figure S3D). To investigate the role of gut bacteria in feed efficiency, we performed FMT from H-FE chickens to L-FE chickens (Figure 1E). As expected, FMT significantly improved feed efficiency (lower FCR) and growth performance (higher weight gain) in L-FE chickens (Figure 1F,G), indicating that microbiota intervention is an effective strategy for enhancing feed efficiency in poultry production. Then, we investigate whether FMT alters the composition and function of gut microbiota and IgA-coated microbiota. Our results revealed that FMT alters the cecal microbial composition and diversity in L-FE chickens to mirror those of H-FE chickens (Figure S4A,B). Interestingly, the relative abundance of Gram-positive Actinobacteria was significantly higher in H-FE and FMT chickens than in L-FE chickens (p < 0.05), while the abundance of Gram-negative Proteobacteria decreased after FMT (Figure S4C). In the IgA-coated microbiota, Bacteroidetes, Synergistetes, and Tenericutes were more abundant in H-FE and FMT chickens than in L-FE chickens (Figure S4D). BugBase predictive analysis revealed that the abundance of Gram-negative bacteria and potential pathogens in the cecal microbiota was significantly higher in L-FE chickens compared to H-FE and FMT chickens. However, no significant differences were observed among the three groups in the IgA-targeted bacteria (Figure 1H). This finding suggests that IgA in L-FE chickens may have a lower affinity for binding pathogenic microbes. To more precisely identify biomarker species associated with feed efficiency, we comprehensively analyzed the cecal and IgA-coated microbiota following FMT. We hypothesized that the core functional taxa would be those microbes that are significantly more abundant in both FMT and H-FE chickens compared to L-FE chickens. At the genus level, the cecal microbiota in FMT and H-FE chickens had higher abundances of Peptococcus, Dorea, and Blautia, and lower levels of Coprococcus and Sutterella compared to L-FE chickens (Figure S4E). Similarly, the IgA-coated bacteria in FMT and H-FE chickens were enriched with Prevotella, YRC22, Enterococcus, and Blautia, while Megamonas and Coprococcus were less abundant compared to L-FE chickens (Figure S4F). We conducted linear discriminant analysis (LDA) to identify biomarker bacteria associated with feed efficiency (threshold ≥ 2). Consequently, Peptococcus, Dorea, and Blautia were identified as biomarker bacteria in the cecal microbiota, while Blaitia was also identified as a biomarker in the IgA-coated microbiota (Figure S5). Among these bacterial genera, only Blautia emerged as a co-biomarker in both the cecal and IgA-coated microbiota (Figure S6). Additionally, a significant negative correlation was observed between the relative abundance of IgA-coated Blautia and FCR (Figure 1I). Thus, through integrated analysis of cecal and IgA-coated microbiota, we precisely identified Blautia as the biomarker genus associated with feed efficiency. Given that IgA is produced by activated B cells derived from the bursa in birds, we examined the size of lymphoid follicles and the proportion of Bu-1+ B cells in the bursa of Fabricius. The data indicated that FMT significantly enhanced both parameters, bringing their levels closer to those observed in H-FE chickens (Figure S7A,B). Blautia is considered as a new functional genus with potential probiotic properties, such as improving metabolic disorders by metabolizing tryptophan into indole-3-acetic acid and preventing inflammation by upregulating intestinal regulatory T cells [18, 19]. However, its impact on feed efficiency remains unclear. Therefore, we administered Blautia coccoides, a potential probiotic with a significant role in regulating host energy metabolism and mucus immunity of the genus Blautia [19, 20], to newborn low feed efficiency chicks and weaned C57BL/6j mice respectively (Figure S7C,D). We found that B. coccoides did not affect the body weight of chickens and mice (Figures 2A, S7E), but significantly reduced the feed intake of L-FE chickens (Figure 2B). Moreover, B. coccoides showed potential in improving feed efficiency in L-FE chickens and mice (Figures 2C, S7F). The FCR of L-FE chickens decreased from 3.86 to 3.75 following B. coccoides administration. A notable increase in IgA-coated bacteria was observed in the cecal contents after B. coccoides administration in both chickens and mice (Figures 2D, S7G). Additionally, significantly elevated levels of CD19+ cells, IgA+ cells, and CD19+ IgA+ cells were observed in the mesenteric lymph nodes of mice following B. coccoides treatment (Figure 2E,F). These results suggested that B. coccoides has the potential to improve feed efficiency and increase the activation of B cells. To further investigate the underlying mechanisms, we cocultured the B-cell line Ramos with B. coccoides in vitro, revealing that B. coccoides significantly stimulated B cell activation, leading to a noticeable increase in the IgA-producing CD19- CD138+ plasma cells and IgA+ cells (Figure 2G,H). This was accompanied by upregulation of genes associated with B cell activation (B lymphocyte-induced maturation protein-1, Blimp1 and X-box binding protein 1, Xbp1s) and IgA production (Immunoglobulin heavy constant alpha 1, Igha1) (Figure 2I–K), along with a notable elevation in IgA secretion (Figure 2L). Similarly, primary B cells isolated from 49-day-old chickens showed enhanced viability and activation when cocultured with B. coccoides, as evidenced by an increased proportion of IgA+ B cells and elevated IgA secretion (Figure S8). While previous studies have highlighted the role of Blautia in T lymphocyte development, its impact on B cells and IgA production had not been reported until now. Further studies utilizing IgA-knockout animals will be crucial to elucidate the underlying mechanisms of the IgA-Blautia interactions in improving feed efficiency. In summary, we demonstrated that H-FE chickens had a greater abundance of Gram-positive and stress-tolerant strains, while L-FE chickens exhibited an increased abundance of harmful bacteria, including Gram-negative microbes and potential pathogens. By integrating analysis of cecal and IgA-coated microbiota, we precisely identified Blautia as a biomarker bacterium, potentially enhancing feed efficiency through the activation of B cells to produce IgA. Thus, our study offers a precision approach to identifying functional probiotics and provides a new strategy for improving feed efficiency in animal production. Sample numbers for 16S rRNA sequencing are listed in Table S4. Detailed procedures for FMT, B. coccoides administration in chickens and mice, coculture of B cells with B. coccoides, sample collection, 16S rRNA sequencing, bioinformatics, and statistical analysis methods are provided in the Supplementary Information. Chunlin Xie: Writing—original draft; funding acquisition; investigation; visualization; formal analysis; validation; writing—review and editing. Jiaheng Cheng: Investigation; validation. Peng Chen: Investigation; validation. Xia Yan: Investigation; validation. Chenglong Luo: Conceptualization; writing—review and editing. Hao Qu: Conceptualization; writing—review and editing. Dingming Shu: Conceptualization; funding acquisition; writing—review and editing. Jian Ji: Conceptualization; funding acquisition; writing—review and editing. Thanks to Professor Hirotada Mori (Innovation Laboratory of Systems Microbiology and Synthetic Biology, Institute of Animal Sciences, Guangdong Academy of Agricultural Sciences, Guangzhou, China) for helpful discussions and critical reading of the manuscript. This work was partially supported by the National Natural Science Foundation of China (Nos. 32302755 and 32172687), the Talent Introduction project of Guangdong Academy of Agricultural Sciences (No. R2022YJ-YB3013), the Science and Technology Program of Guangdong Province, P. R. China (No. 2022B0202160009), the Special Fund for Scientific Innovation Strategy-Construction of High Level Academy of Agriculture Science (No. R2023PY-JG012), the Project of State Key Laboratory of Swine and Poultry Breeding Industry (No. 2023QZ-NK02 and GDNKY-ZQQZ-K1), and the CARS-Meat-Type Chicken (No. CARS-41). The authors declare no conflicts of interest. All experimental procedures were performed in accordance with the guidelines for the Institutional Animal Care and Use Committee of the Institute of Animal Science, Guangdong Academy of Agricultural Sciences (Approval Nos. 2023007 and Q021), Guangzhou, China. The details of material and methods are available in the supplementary materials. Raw data for 16S rRNA gene sequencing for cecal and IgA-coated microbiome can be accessed at Sequence Read Archive (SRA) database with accession number PRJNA994595 (https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA994595). The data and scripts used are saved in GitHub https://github.com/cylinqueen/chicken-micro. Supplementary materials (methods, figures, tables, graphical abstract, slides, videos, Chinese translated version, and update materials) may be found in the online DOI or iMeta Science http://www.imeta.science/. Figure S1. Dynamic alterations in the microbial community during the growth of L-FE and H-FE chickens. Figure S2. Differential functions analysis of the cecal microbiota based on PICRUSt prediction between L-FE and H-FE chickens. Figure S3. Composition and function of IgA-coated microbiota between L-FE and H-FE chickens. Figure S4. Effects of FMT on cecal and IgA-coated microbial diversity and composition. Figure S5. Identification biomarker bacteria associated with feed efficiency. Figure S6. Boxplots display the relative abundance of shared bacterial taxa identified by LDA score analysis. Figure S7. FMT on chickens and B. coccoides administration in chickens and mice. Figure S8. Primary B cells of chicken co-culture with B. coccoides. Table S1. The significant differences of microbial composition at the phylum and genus levels. Table S2. Relative abundance of cecal microbiota at the phylum level. Table S3. Relative abundance of cecal microbiota at the genus level. Table S4. Sample number for 16S rRNA sequencing. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Tilmicosin, an antibiotic widely used in animal husbandry to prevent and treat bacterial infections, raises concerns due to its residual accumulation, which impacts both animal health and food safety. In this study, we conducted a comprehensive analysis of tilmicosin clearance patterns in different tissues, assessed physiological impacts through blood biochemistry, and investigated changes in gut microbial composition with 16S rRNA sequencing of the tilmicosin-treated Silkie chickens. Initially, we observed rapid peaks in tilmicosin residues in all tissues within 1 day after treatment, but complete metabolism took longer, extending beyond 9 days. Moreover, tilmicosin treatment significantly decreased serum levels of total bile acid, blood urea nitrogen, and uric acid, while increasing the levels of direct bilirubin, total bilirubin, and glutathione peroxidase at day 3, followed by a decrease from day 5 onwards. The effects of tilmicosin use on microbial composition and diversity lasted for an extended period, with the relative abundance of Proteobacteria remaining significantly different between the control and tilmicosin-treated groups at 120 days. Additionally, correlation analysis revealed a strong positive correlation between Mucispirillum_schaedleri and tilmicosin residue in all tissues, while Parabbacteroide_distasonis, Faecalibacterium_prausnitzii, and others exhibited negative correlations with tilmicosin residue. Overall, our study indicates a significant correlation between intestinal microbes and antibiotic residues, providing a theoretical basis for guiding the withdrawal period after antibiotic use.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)