<h1 toutiao-origin="h1" > Chinese scientists to complete the construction of the chicken gut microbial macrogene set</h1>
Recently, the research team of Professor Zeng Jianguo of Hunan Agricultural University has made breakthroughs in the construction of reference macro gene sets in chicken intestines and the growth promotion mechanism of antibiotics and plant-derived natural growth promoters. His research results, titled "The chicken gut metagenome and the modulatory effects of plant-derived benzylisoquinoline alkaloids", were published in the form of a long research article (IF: 11.607) published online.
图1. The chicken gut metagenome and the modulatory effects of plant-derived benzylisoquinoline alkaloids
< h2 toutiao-origin="h2" > article interpretation</h2>
Since scientists discovered in the 1950s that subtherapeutic doses of antibiotics can be used as antibiotic growth promoters (AGPs), antibiotics have been widely used and brought great benefits to the aquaculture industry, but they have also posed a serious threat to public health by boosting the formation of drug-resistant bacteria. Since 2006, the addition of feed antibiotics has been completely banned in Europe, and in 2017, the United States also banned the use of antibiotics in feed to promote growth and placed them under veterinary clinical supervision. This was followed by a 2020 Plan to Curb Drug Resistance, which will ban the use of feed antibiotics altogether in 2020. Therefore, it has become very important and urgent to develop green and safe alternatives. In recent years, plant-derived natural growth promoters (NGPs), such as Macleaya cordataextract, MCE, haematine and celandine components, etc., have gradually entered people's field of vision as feed substitute products. At present, the products containing BoLuohui extract (Sangrovit® and "Boluohui (Meiyouzhuang ®)") have been sold well in more than 70 countries and regions. However, the mechanism of action of either AGPs or NGPs is unclear. Only by elucidating the disease-proof and growth-promoting mechanism of feed antibiotics (AGPs) can we truly guide the development of naturally derived disease-proof and growth-promoting feed substitution products. This gene set is another animal gut microbial reference macro gene set after the gut microbial gene set of humans, mice, pigs and dogs. As an important livestock and poultry animal, chickens provide humans with cheap and high-quality animal proteins such as meat and eggs, but large-scale research on the macro gene set of chicken gut microorganisms is still relatively lacking. Recently, the research team of Professor Zeng Jianguo of Hunan Agricultural University has made breakthroughs in the construction of reference macro gene sets in chicken intestines and the growth promotion mechanism of antibiotics and plant-derived natural growth promoters. His research results, titled "The chicken gut metagenome and the modulatory effects of plant-derived benzylisoquinoline alkaloids", were published in the form of a long research article (IF: 9.13) published online (Figure 1).
Previously, Jianguo and Huang Sanwen's team had successful collaborative research in cucumber and Boluo back genome and synthetic biology, this time it was once again joint with the Shenzhen Genomics Research Institute of the Chinese Academy of Agricultural Sciences led by Huang Sanwen, and the team of Fan Wei researchers and Professor Yu Yuming of China Agricultural University achieved the results, the research was first launched in 2012, and it took 6 years to successfully construct a chicken intestinal microbial reference gene set and systematically compare and study antibiotic growth promoters (chlortetracycline, CTC) based on this gene set. and the effects of plant-derived growth promoters (Bo DropBack Extract, MCE) on chicken gut microbes. This achievement is an important supplement to the study of animal intestinal metagenomics, and what is more gratifying is that it provides a supporting basis for the development of alternatives to feed antibiotics.
< h2 toutiao-origin="h2" > the background of the paper</h2>
Although the use of antibiotic growth promoters (AGPs) has made a significant contribution to the healthy breeding of animals, since the use of low-dose antibiotics as growth promoters, it has been accompanied by bacterial resistance and superbug problems, posing a potentially serious threat to the environment and public health. Sweden took the first step back in 1986, declaring a total ban on antibiotics as feed additives. Subsequently, Denmark has also banned the use of a variety of antibiotics as growth promoters. In 2006, the European Union completely stopped using all AGPPs. The United States has also banned the addition of antibiotics to feed for growth promotion since 2017, placing them under veterinary supervision. China's Ministry of Agriculture has also developed a National Action Plan to Curb Bacterial Resistance (2016-2020), which will completely ban the use of feed antibiotics by 2020. Therefore, the search for "safe, effective, controllable and low-cost" feed substitute antibody products is currently a hot topic in global research. There have been reports that low-dose antibiotics do not increase the weight of sterile chickens, so it has been inferred that the effects of antibiotic growth promoters are closely related to the gut microbiome. At present, the study suggests that AGPs may achieve growth-promoting effects by inhibiting subclinical infections and reducing growth inhibition metabolites produced by intestinal microorganisms, but the more in-depth growth promotion mechanism is still unclear. Only by elucidating the mechanism of disease prevention and growth promotion of AGPs can we truly guide the development of naturally derived disease prevention and growth-promoting feed substitution products. Further research is therefore needed to advance our understanding of AGPs.
For a long time, plant-derived natural growth promoters, such as products containing Boluohui extract, have been widely used in livestock and poultry production as alternatives to antibiotics, and were successfully approved in China at the end of 2012, becoming China's first class II new Chinese veterinary drug feed additive product. Clinical trials have proved that Boluo dispersion has a good anti-inflammatory, intestinal health and growth promotion effect on pigs, chickens and aquatic products. Active chemical constituents of Boluf dispersion include kaematine and celandine, both of which belong to a group of benzyl isoquinoline alkaloids with antibacterial and anti-inflammatory properties. In addition, another kind of benzyl isoquinoline alkaloid - berberine (also known as berberine), which has a highly similar molecular structure with kazine, which effectively treats dysentery and enteritis in the clinic by regulating the intestinal microbiota, Chinese scientists Professor Zhao Liping and Professor Jiang Jiandong have in-depth research on the intestinal regulation of berberine and the role of hypoglycemic and lipid-lowering. Although the global market for feed substitute products developed based on Boluohui extract has achieved impressive results, the details of the mechanisms related to improving the performance of livestock and poultry production are still unclear.
Traditional 16S rRNA gene analysis provides only limited information about the composition of microorganisms, and the continuous advancement of metagenomic sequencing technology has provided important technical support for the functional study of intestinal microorganisms. In recent years, through large-scale sequencing of hundreds of samples, macrogene sets of gut microbes in humans, mice, pigs, and dogs have been gradually established, each containing millions of non-redundant genes, laying the foundation for studying the function of this set of host symbiotic "second genomes". Therefore, in order to better understand the function of poultry gut microbes and explain the interaction between AGPs, NGPs and intestinal microbiota, the research team led by Professor Zeng Jianguo of Hunan Agricultural University, together with the team of researcher Fan Wei of the Shenzhen Genomics Research Institute of the Chinese Academy of Agricultural Sciences, and the team of Professor Yu Yuming of China Agricultural University, launched the chicken intestinal metagenomic research program in 2012. After 6 years of efforts, the first chicken intestinal microbial reference gene set was constructed, and the effects of different intestinal segments (duodenum, jejunum, ileum, cecum, colorectal), different feeding methods (free range chickens and caged chickens), and different day ages (1-42 days old) on the intestinal microbial community and function were deeply analyzed. Finally, the regulatory effects of chlortetracycline (CTC) and Bolurgyn extract (MCE) on the gut microbiota were systematically compared. These results reveal significant differences in the effects of CTC and MCE on the gut microbiota, indicating the great potential of MCE as an alternative product to feed antibiotics in poultry farming.
<h2 toutiao-origin="h2" >1. Comparison of chicken intestinal macrogene sets with human and pig intestinal macro gene sets</h2>
Fig. 2 Chicken intestinal macrogene set.
(a) Chicken gut diagram. Foregut (duodenum, jejunum, ileum) and hindgut (cecum, colorectum) and their microbial density. (b) Dilution curves for the number of detected genes from 495 samples (total) and samples from yellow chicken (LY), white feather chicken (AA) and samples from different regions.
Unlike previous studies in human, mouse, and pig macro gene sets that selected feces as research materials, the study selected samples of different intestinal segment contents that are more representative of the gut microbiome as research materials. The researchers collected 495 intestinal contents samples (Figure 2a) from 5 intestinal segments (duodenum, jejunum, ileum, cecum and colorectal) of chickens raised on 7 different farms in China, yielding a total of 1.64 Tb of metagenomic data (an average of 3.31 Gb per sample) by high-throughput sequencing. Based on assembled contigs (contigs) of 1.95 kb in length N50, 9.04 million non-redundant genes were identified, with an average open reading frame (ORF) length of 697 bp. The sample dilution curve shows that the curve is close to saturation (Figure 2b), indicating that the vast majority of genes for chicken gut microbes are already contained in this gene set. The size and quality of this gene set are comparable to those of the human intestinal macro gene set (9.9 million genes) and the porcine intestinal macro gene set (7.7 million genes), which can provide a useful reference gene set for follow-up studies. Through pairwise comparisons, it was found that at the gene sequence level, more than 80% of the genes are unique in each species, and the proportion of gut microbial genes in chickens, people and pigs is very low (~0.5%). In addition, chickens and pigs have fewer common microbial genes (~0.8%) than chickens and humans (~10%) or pigs and humans (~10%) (Figure 3). Using CAMRA3 for classification, 80.99% of the genes in the chicken intestinal gene set can be classified at the total boundary level, of which bacteria account for 98.95% of the classified genes and the remaining 1% come from archaea and eukaryotes. More than 88% of bacterial genes come from four main phyla, phylum Pachychycetes, Actinomycetes, Proteus and Bacteroides.
Figure 3. Comparison of human, pig and chicken intestinal macrogene sets
(a) Genetic sequence comparison of human, pig and chicken intestinal macrogene sets. (b) Venn diagrams present in the chicken, human, and pig gene sets and their shared KEGG orthogenetic homology (KOs).
In the human and pig intestinal gene concentrations, the phylum Pachychycetes and Bacteroides phylum dominate, and the Phylum Proteobacteria and Actinomycetes phylum account for a relatively small proportion. At lower taxonomic levels, 25.97% and 2.29% of genes in the gene set can be annotated to the level of gene and species. The genera that produce short-chain fatty acids (SCFA), such as Bacteroides, Blautia, Ruminococcus, and Faecalibacterium, are both the dominant genera of human and pig gut microbes and the relatively high abundance in the chicken gut, suggesting the importance of such gut microbes in birds and mammals. After that, functional gene classification is performed using KEGG and eggNOG. The results showed that although the gene set of chickens differed greatly from those of humans and pigs at the gene sequence level, the functional similarities of common gut microbes were high. It is worth noting that genes related to glycan biosynthesis and metabolism are relatively abundant in the intestines of humans and pigs, while genes related to membrane transport (including genes related to sugar, lipid, peptide and ion substrate uptake) are relatively abundant in chicken intestines. The higher abundance of membrane transport-related genes may be due to the fact that multiple nutrient substrates in the chicken gut are more easily utilized directly by microorganisms. The degradation of heterotypic biomass in the chicken intestine, the genes of terpenoids and polyketone compound metabolism also have a high relative abundance, which is related to the relative abundance of actinomycetes in the chicken intestine, which has the characteristics of decomposing organic matter and producing various natural drugs, enzymes and biologically active metabolites.
<h2 toutiao-origin="h2" >2. Effects of different breeding patterns on the intestinal metagenomics of chickens</h2>
The intestinal microbial diversity (Shannon index) of chickens was higher in free-range mode (DHC and DGY) than in cage mode (DHK, DSL and DST) (Figure 4a). In addition, actinomycetes, the main component of the soil flora, are also more abundant in free-range chickens than in caged chickens (Figure 4b). Free-range chickens are exposed to the outdoor environment and come into contact with a more diverse microbiota, thus having a different gut microbial composition.
Figure 4. (a) Sample microbial diversity (Shannon index) of gene, genus, OG and KO levels in five regional groups (DGY, DHC, DHK, DSL, DST). (b)Average relative abundance of actinomycete phylum in foregut samples from five regional groups (DGY, DHC, DHK, DSL, DST).
< h2 toutiao-origin="h2" >3. Different characteristics of the foregut and hindgut metagenomes of chickens</h2>
The study analyzed metagenomic data from 285 intestinal samples (containing 5 intestinal segments) using chickens over 40 days old. The analysis found that the microbial diversity of the foregut segment (duodenum, jejunum and ileum) was about the same, and the diversity of the hindgut (cecum and colorectum) was also about the same, but the difference between the anterior and posterior intestines was larger, and the diversity of the hindgut was significantly higher than that of the foregut. Through the analysis of the relative abundance distribution of microorganisms, it was found that Lactobacillus was an absolute dominant genus in the foregut. Lactobacillus is known to provide nutrients to the host and protect against opportunistic pathogenic bacteria. Analysis of symbiotic networks of the genus Central foregut showed (Figure 5) that in the foregut, Lactobacillus was competitively inhibiting some bacteria, and the relative abundance of these bacteria was inversely correlated (Figure 5a). In addition, some short-chain fatty acid (SCFA) producing bacteria, such as Clostridium, Bacillus butyric acid, and Faecalibacterium, are positively correlated with each other and form a relatively independent and stable network structure in the foregut (Figure 5a). In the hindgut, there are 19 genera that are positively correlated with each other and form a large central symbiotic network (Figure 5b), which contains beneficial intestinal microorganisms and has the effect of inhibiting opportunistic pathogenic bacteria (Escherichiae and Enterococcus) (Figure 5b). These results reveal a more diverse and complex microbiota in the hindgut than the foregut.
Figure 5. Analysis of the genus symbiotic networks of the core microbial genus of (a) foregut and (b) hindgut of chickens
KEGG functional analysis showed that the relative abundance of microbial flora in the foregut was higher than that of the hind intestine in terms of replication, transcription, translation of genetic information processing, and nucleotide and lipid metabolism; amino acid metabolism, energy metabolism, and biosynthesis of secondary metabolites in the hindgut were relatively higher, which was consistent with the phenomenon that a large number of microorganisms produced multiple metabolites (such as amino acids and SCFA) in the fermentation of the hind intestine. At the same time, the study believes that the advantages of the genus Lactobacillus in the foregut and the genomic characteristics of the genus Lactic acid bacteria contribute to a large extent to the characteristics of the foregut microbiome and the functional differences between the anterior and posterior intestines. In summary, the classification and functional characteristics of the microbiome of the foregut and hindgut are consistent with the morphology and physiological structure of the chicken intestine.
<h2 toutiao-origin="h2" >4. Changes in the intestinal flora of chickens with age and gradual maturation</h2>
To investigate the temporal variation characteristics of the gut microbial community, the study analyzed samples from two breeds, white-feathered broiler (AA) and yellow chicken (LY), at 5 days of age (1, 7, 14, 28 and 42 days old). The results showed that the intestinal microbial samples of the chicks (1 day old) varied greatly from each other and were significantly different from other day-olds (Figure 6), reflecting the state of the chicks at first contact with environmental microbes and beginning to establish a community of gut microbes. The development and change of the microbial flora is affected by many factors (such as diet, feed additives, host varieties, etc.). For AA and LY chickens, NMDS plots show that samples can be grouped roughly according to different day-age clusters and show higher similarities at days 28 and 42 (Figure 6). Throughout the growth test, the pachylococcal, proteus, Bacteroides, and Actinomycetes phylum were always bacteria in the foregut and hindgut, and all showed significant patterns of change over time. For example, the bacterial phylum with the highest relative abundance, the Phylum Pachylobacterium, gradually increases in the foregut from day 1 to day 28 and then remains relatively stable, while in the hindgut, the Phylum Pachylobacter decreases slowly from day 7 to day 42. In both the foregut and the hindgut, the metabolic capacity of microorganisms reached its maximum value on day 28 and remained roughly stable thereafter; however, the degree of difference in age between different days in the foregut was greater than the difference in age in the hindgut. In summary, early stage is crucial for both the development of chickens and the establishment of the gut microbiome.
Figure 6. Differences in the microbiome of chicken intestines at different day ages. (a) NMDS plots of the foregut microbial communities of different days of age. (b) NMDS plots of intestinal microbial communities after different days of age.
<h2 toutiao-origin="h2" >5. The role of chlortetracycline and borophoric extracts in regulating the microflora of the foregut to promote animal growth</h2>
Through growth performance testing, the effects of CTC and MCE (low L, medium M, high H3 doses) as low-dose feed additives in yellow chicken (LY) and white-feathered broiler (AA) were compared. The results showed that the effect of body weight gain increase and material-meat ratio (FCR) decrease in the dose group (MCE-M) of Bo Fallback Extract was better than that of the Chlortetracycline Group, and this dose was also in line with the commercially promoted dose, indicating that Bo Fallback Extract was superior to Chlortetracycline in terms of growth promotion effect, which was of great significance for the aquaculture industry. The relative expression of cytokines in the ileum of white-feathered broilers showed that both CTC and MCE could downregulate host cytokines including IL-4, IFN-γ and NF-κB, indicating that both had the effect of inhibiting host inflammation and immune response.
The effects of CTC and MCE on chicken gut microbes are mainly in the foregut, while the effect on the hindgut is smaller. In the foregut, Lactobacillus spp. is the main genus affected by MCE (Figure 7a), and the dominant position of Lactobacillus spp. in the foregut can be further strengthened by MCE. Lactobacillus is known to be a beneficial probiotic that produces nutrients such as vitamins and organic acids, and also competitively inhibits pathogens, benefiting the health of the host. In addition, through the "cross feeding" mechanism, the lactic acid produced by Lactobacillus can also be used by anaerobic bacteria to produce butyric acid, which is an important source of energy for intestinal cells and exerts anti-inflammatory effects.
Figure 7.(a) Changes in microorganisms in the foreguel after CTC and MCE treatment. (b) Increased relative abundance of antibiotic biosynthetic pathways in the chlortetracycline group. (c) The relative abundance of antibiotic resistance genes (ARGs) in the chlortetracycline group increased.
Unlike MCE, CTC significantly increases the relative abundance of Streptomyces microorganisms (Streptomyces and Kitasatospora), which include a variety of bacteria that synthesize antibiotics. Further analysis found that the synthetic pathways of tetracycline, macrolides, type II polyketones, and clavulanic acid (synergists for penicillin antibiotics) were significantly enhanced in the chlortetracycline group (Figure 7b). In addition, antibiotic resistance genes (ARGs) have also increased (Figure 7c). In contrast, none of the above results were produced in the Bo Fallback Extract group, further demonstrating the safety of bo-fallback extract, a natural plant-derived antibiotic replacement product. These findings provide new perspectives for explaining the pro-growth mechanisms of subtherapeutic dose antibiotics.
By analyzing the effects of MCE and CTC on intestinal microbial function, it was found that both had important effects on lipid metabolism and could enrich secondary bile acid biosynthetic pathways. The bile acids secreted by the host are known to have antibacterial activity that alters the composition of the gut microbiome; while the secondary bile acids produced by microbial modification can promote fat absorption and participate in regulating the host's energy metabolism and immune system. In addition, CTC also enhances the biosynthetic pathways of fatty acids and unsaturated fatty acids, which suggests that lipid metabolism regulation is an important mechanism for antibiotic growth promoters. MCE, on the other hand, promotes nutrient absorption and growth in chickens by enhancing biosynthetic pathways of amino acids and vitamins (Figure 8).
Figure 8. Significant changes in the metabolic pathway of CTC and MCE on the foregut microbiome KEGG.
< h2 toutiao-origin="h2" > summary</h2>
In summary, this study found that both growth promoters play an important regulatory role in the foreguel microorganisms of chickens. BoLurgy extract (MCE) improves growth performance and regulates the foregut microbiota in chickens, and its effects include promoting the increase of the beneficial bacteria Lactobacillus spp., as well as enhancing the biosynthetic pathways of amino acids, vitamins and secondary bile acids. The increase in the genus Lactobacillus can also lead to a reduction in host inflammation and immune response through competitive inhibition of the role of pathogenic bacteria. Chlortetracycline (CTC) can promote streptomyces (Streptomyces and Kitasatospora) microorganisms in the intestine, and may achieve the effect of regulating the intestinal flora by promoting the synthesis of various antibiotics in some bacteria. In addition, CTC also has an important regulatory effect on secondary bile acid and lipid metabolism (Figure 9), thus affecting nutrient absorption by the host. This study is an important study of the mechanism of animal growth promoters and provides important support for the development of safe and effective alternatives to feed antibiotics.
Figure 9. The speculative mechanism by which CTC and MCE regulate the intestinal microbial flora to promote animal growth.
This achievement was completed by a number of units, and received strong funding from the 13th Five-Year Plan of the Ministry of Science and Technology of the National Key Research and Development Program of "Modernization of Chinese Veterinary Medicine and Green Breeding Technology". Huang Peng, phD student of Hunan Agricultural University, Zhang Yan, postdoctoral fellow of Genomics Research Institute of Chinese Academy of Agricultural Sciences, Xiao Kangpeng, ph.D. student of Hunan Agricultural University, and Jiang Fan, postdoctoral fellow of Genomics Research Institute of Chinese Academy of Agricultural Sciences, are the co-first authors of the paper. Professor Yu Yuming of China Agricultural University, Fan Wei, Researcher of Agricultural Genome Research Institute of Chinese Academy of Agricultural Sciences, and Professor Zeng Jianguo of Hunan Agricultural University are co-corresponding authors.
< h2 toutiao-origin="h2" > expert reviews</h2>
< h2 toutiao-origin="h3" > Professor Zhang Heping commented</h2>
Expert introduction
Professor Zhang Heping, male, Ph.D., professor, doctoral supervisor of Inner Mongolia Agricultural University, was awarded the National Outstanding Youth Science Fund in 2010, the Distinguished Professor of the "Yangtze River Scholars" Award Program in 2012, the "National Hundred Million Talents Project" in 2013 and the title of "Young and Middle-aged Experts with Outstanding Contributions", in 2015, he was selected as the National Outstanding Talents in Agricultural Scientific Research, and in 2016 he was selected as the Leading Talents of Scientific and Technological Innovation in the National "Ten Thousand Talents Program". He has won the "Inner Mongolia Autonomous Region Science and Technology Special Contribution Award" (2013), the "He Liang He Li Science and Technology Innovation Award" (2015), and the Ministry of Agriculture's 2017 "Shennong Chinese Agricultural Science and Technology Award - Excellent Innovation Team Award".
He is currently the head of the Key Laboratory of Dairy Biotechnology and Engineering of the Ministry of Education, the Key Laboratory of Dairy Product Processing of the Ministry of Agriculture and Rural Affairs, and the National and Local Joint Engineering Laboratory of Lactic Acid Bacteria Screening and Dairy Fermentation Technology.
He has published more than 150 papers as the first author or corresponding author in SCI-indexed journals such as Nature Communication, The ISME Journal, Microbiome, and Molecular and Cellular Proteomics. A variety of probiotic strains have been developed for wide application in the food industry, medical health, animal farming and other fields.
Comments
The heavy use of feed antibiotics poses a serious threat to public health, so reducing or even banning the use of feed antibiotics and finding suitable alternatives has attracted global attention. Today, some naturally derived feed antibiotic replacement products are gradually joining the ranks of growth-promoting feed additives to replace antibiotics with their effects of improving the balance of host intestinal flora, promoting digestion and absorption, and enhancing immunity. The study studied the modulation of intestinal and anti-inflammatory effects of Chinese veterinary drug feed additives made of benzofidine alkaloids extracted from natural plant Bolurgyn (mainly kazalin, celandine red alkali) extracted from the natural plant Bolurgyn, and used the forage antibiotic chlortetracycline as a positive control to explain the different mechanisms of action of the intestinal flora in antibiotic growth promoters and plant-derived natural growth promoters, reminding that the beneficial regulation and inflammation inhibition of intestinal flora are important concerns in the development of forage antibiotic alternatives. It is worth noting that the study for the first time found that low-dose antibiotics can produce more kinds of antibiotics and antibiotic synergists in the foregut of chickens, which further supports the need for banning antibiotics for feeding; the study also shows that chlortetracycline and Boluo dispersion have the effect of inhibiting host inflammation and immune response; the result is another animal intestinal reference macro gene set after humans, mice, pigs, and dogs. This study provides a new theoretical guide for the research and development of feed substitute antibody products and has the scientific and technical value of targeted industrial guidance.
< h2 toutiao-origin="h3" > Professor Wei Hong's comments</h2>
Wei Hong: Professor and doctoral supervisor of the Third Military Medical University of the People's Liberation Army of Chinese. Using sterile animal and genetic engineering techniques, the effects of host genes and intestinal microbial interactions on the physiological and pathological phenotype of the body were studied. Establish the most influential sterile animal platform in China, and effectively support the research of intestinal flora in the fields of medicine, food, and animal husbandry in China. Establish a pig genetic engineering technology system, create a series of gene editing pigs, and obtain serum albumin humanized pigs. Multiple diseased pig families were created using ENU technology. He has published 86 SCI papers in Science et al., with an impact factor of 421. He has published 60 SCI papers in Nature Immunology et al., with an impact factor of 229. 17 invention patents have been authorized. The cooperative research and development of "gene transfection of pig skin" has obtained the SFDA registration certificate and clinical application. The editor-in-chief of "Medical Laboratory Zoology" was the first batch of national postgraduate teaching books recommended by the Ministry of Education of the People's Republic of China, and the editor-in-chief of "Medical Animal Experimental Technology" was funded by the National Science and Technology Academic Book Publishing Fund.
The mechanisms by which low-dose antibiotics promote growth are not well understood until they are banned globally due to resistance issues, but alternatives to what are marketed as feed antibiotics are on the rise. Metagenomic sequencing studies based on microbial in vitro culture and small-scale samples have found that both feed antibiotics and the growth promotion effects of their natural alternative products are closely related to the gut microbiome, but due to the lack of large sample size analysis of big data and the lack of samples that can better represent the microbial situation in the intestine, it has been impossible to clearly analyze the mechanism of action of the two. Only by elucidating the disease prevention and growth promotion mechanism of the two can we truly guide the development of natural source disease prevention and growth-promoting feed substitution products. The paper found through the study of chicken intestinal metagenomic data that both growth promoters mainly act on the foregut microbiota of chickens, and the effect on the hindgut microbiome is small, which is mainly due to the selection of intestinal contents that can best represent the intestinal microbial community in the previous experimental materials. Interestingly, the study confirmed that the intestinal regulation mechanisms of the two growth promoters are very different. Bo fallback extract (the substance component is very clear isoquinoline alkaloid mixture, MCE) mainly promotes the increase of the beneficial bacteria Lactobacillus spp., while the increase of Lactobacillus spp. will competitively inhibit pathogenic bacteria and lead to a reduction of host inflammation and immune response response, thus achieving the purpose of "anti-inflammatory growth" in farmed animals. It can enhance the biosynthetic pathways of amino acids, vitamins, butyric acids and secondary bile acids to provide nutrients and anti-inflammatory substances to the host to achieve growth-promoting effects, and the results of the detection of inflammatory factors in intestinal tissues in the study results further support this theory. Unlike Boluo's relapse, low-dose chlortetracycline (CTC) is likely to promote the abundance of the microbiota of streptomyces (Streptomyces and Kitasatospora) in the intestine, resulting in increased synthesis of multiple antibiotics in the intestine and inhibition of harmful flora and inflammatory responses to achieve growth-promoting effects. Although both growth promoters produce the same results, low doses of antibiotics cause a significant increase in antibiotic resistance genes in the intestine and do not. Therefore, the development of feed substitute products with "beneficial flora regulation, anti-inflammatory, and growth promotion" is the future research goal. In general, as an important supplement to the study of intestinal metagenomics, this study provides important data support for better understanding the function of intestinal microorganisms in poultry, and provides theoretical guidance for the development of key technologies and applications of alternatives to feed antibiotics, which will also accelerate the development and basic research process of feed substitution products; at the same time, the research also provides reference for the construction of other macrogenes and the study of microorganisms and hosts. It is invaluable that the team has achieved such forward-looking innovations in the field of Veterinary Medicine. Congratulations to Professor Zeng Jianguo's team!
< h2 toutiao-origin="h3" > Qin Nan researcher commented</h2>
Qin Nan: Founder of Shanghai Ruiyi Biotechnology Co., Ltd., researcher of the Tenth People's Hospital Affiliated to Tongji University, standing committee member of the Microecology Branch of the Chinese Preventive Medicine Association, vice chairman of the Youth Committee, deputy leader of the Digestion and Nutrition Group, and has been awarded the title of "Great Challenge Young Scientist" by the Ministry of Science and Technology and the Gates Foundation. Master supervisor of Institute of Microbiology, Chinese Academy of Sciences, corporate tutor of ShanghaiTech University, Ph.D. in Microbiology, Virginia Tech University, USA. From 2008 to 2011, he served as the head of the microbial genome department of BGI, and from 2011 to 2016, he was a distinguished researcher and doctoral supervisor of the Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases in Zhejiang University School of Medicine. Current research areas include infectious diseases, metabolic diseases, autoimmune diseases, tumor immunotherapy and the relationship intestinal microbiota, the long-term goal of these research is to develop new technologies for the diagnosis, prevention and intervention of the gut microbiome related to human health. Since 2009, he has published more than 30 papers in top international academic journals such as Nature, Science, and PLOS Biology.
In the field of animal breeding, sub-therapeutic doses of antibiotics as animal growth promotionrs (AGPs), bring great benefits to the aquaculture industry, but the problem of bacterial drug resistance is becoming increasingly prominent, posing a threat to the health and public safety of all human beings, causing people's increasing concern. Since 2006, the European Union has completely banned the feeding of antibiotics in animals, followed by China's "2020 Plan to Curb Drug Resistance" to completely ban the use of antibiotics for feeding. At present, controlling, reducing and canceling the breeding use of long-term low-dose antibacterial growth-promoting drugs is the development trend of the future aquaculture industry. Natural growth promoters (NGPs), such as probiotics, probiotics and plant biologics, have been developed as alternatives to antibiotics in livestock. Both AGPs and NGPs promote animal growth are related to the microbiota, but the specific mechanism of action is not yet clear, this study uses metagenomic sequencing technology to study the effects of AGPs and NGPs on the composition and function of chicken gut microorganisms, which helps to understand more deeply the mechanism of action of promoting growth.
Based on the metagenomic data of duodenum, jejunum, ileum, cecum and colon of chickens from 7 different farms and different growth periods, this study constructs the gene set of chicken intestinal microorganisms for the first time, which provides valuable big data resources for future intestinal metagenomic research. In humans and animals, the foregut was less studied, but this study compared the differences in the composition of the foregut and hindgut microbiomes, and analyzed the interaction patterns of the foregut and hindgut microorganisms, and the results showed that the microbial communities of the hindgut were more diverse and complex than those of the foregut. The analysis of intestinal microbiomes of different days of age found that the intestinal flora changes with time in different intestinal segments, and its metabolic capacity reached the highest in 15-28 days. In this study, the regulation and anti-inflammatory growth effects of chlortetracycline and Boluo dispersion (haematoids) on the intestinal flora of chickens were compared, and the differences in the pro-growth mechanisms of the two were elucidated respectively. It was found that chlortetracycline significantly increased the relative abundance of streptomyces microorganisms with the function of synthesizing multiple antibiotics, corresponding to the synthesis pathways of tetracycline, macrolides, type II polyketones and clavulanate (synergist of penicillin antibiotics) in the chlortetracycline group, and the antibiotic resistance gene also increased. The results imply that low-dose antibiotics can elicit a wider variety of antibiotics in the foregut, further warning us of the importance of developing feed replacement products, and these findings provide new perspectives to explain the mechanisms by which low-dose feed antibiotics are effective.
It is believed that this study provides basic support for the feed substitution anti-resistance technology and product development advocated by Professor Zeng Jianguo for "intestinal integrity, anti-inflammatory, and growth promotion". Characteristic studies of the intestinal flora and microbiota function may be used as a means of assessing the safety of feed substitution antibody.
< h2 toutiao-origin="h2" > Professor Zeng Jianguo's profile</h2>
Professor/Doctoral Supervisor of Hunan Agricultural University, Leader of veterinary medicine degree program in Veterinary Medicine. Director of the National and Local Joint Engineering Research Center for Veterinary Chinese Medicine Resources and Chinese Veterinary Drug Creation, director of the Hunan Provincial Key Laboratory of Chinese Veterinary Medicine. Head of the National Agricultural Scientific Research Outstanding Talents and Innovation Team, And a post scientist of the National Chinese Herbal Medicine Industry Technology System. He is also a member of the Chinese Veterinary Pharmacopoeia Committee, a member of the National Feed Review Committee, the vice chairman of the Animal Pharmacology Branch of the Chinese Society of Animal Husbandry and Veterinary Medicine, and a member of the "Zhongyou" and "Chinese Veterinary Drug Promotion Committee" of the Chinese Veterinary Drug Association. As a promoter of China's plant extract industry, he proposes a standardized production system of "two standards and three procedures" to promote the product development and comprehensive utilization and development of traditional Chinese medicine resources in the field of agricultural inputs. The "BoLuohui Extract" was developed into the country's first Class II Chinese veterinary drug feed additive, and sold in more than 70 countries and regions such as Europe and the United States; engaged in the research and development of feed plant raw materials and extract feed additive products; and proposed the "intestinal, anti-inflammatory, growth-promoting" feed antibiotic alternative technology. A fine genome-wide map of Bo fallback plants and a reference gene set of chicken gut microbials were constructed. He has presided over or participated in nearly 20 research projects at the national, provincial and ministerial levels, and is the chief expert of the national key research and development plan of "Modernization and Green Breeding Technology of Traditional Chinese Veterinary Medicine" in the 13th Five-Year Plan. He has published more than 100 academic papers in MP, NP and other domestic and foreign journals, won 2 first prizes of provincial scientific and technological progress, 1 Chinese patent award, and obtained more than 30 invention patents.
Article home page https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-018-0590-5
引文 Huang, P., Zhang, Y., Xiao, K., Jiang, F., Wang, H., Tang, D., Liu, D., Liu, B., Liu, Y., He, X., Liu, H., Liu, X., Qing, Z., Liu, C., Huang, J., Ren, Y., Yun, L., Yin, L., Lin, Q., Zeng, C., Su, X., Yuan, J., Lin, L., Hu, N., Cao, H., Huang, S., Guo, Y., Fan, W., and Zeng, J. (2018). The chicken gut metagenome and the modulatory effects of plant-derived benzylisoquinoline alkaloids. Microbiome 6, 211.
10,000+: Microbiota Analysis Baby & Dog Syphilis Rhapsody Mention DNA Hair Nature Cell Special Issue Intestinal Conduction Brain
Tutorial Series: Getting Started with the Microbiome Biostar Microbiome
Professional Skills: Academic Charts High Score Essays Student Letter Treasure Book Indispensable Person