Development of a Controllable Intelligent Drug Delivery System for Efficient Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complex inflammatory disease of the joints, which is often accompanied by degeneration of articular cartilage and bone erosion, seriously affecting the quality of life and psychological state of patients. RA is difficult to be cured completely, and currently the main purpose of relief is through the use of anti-inflammatory and antirheumatic drugs, hormones, and biological agents. Tofacitib is a new type of small molecule inhibitor, which has a good effect in the treatment of RA. The current direct drug delivery method has serious side effects caused by the systemic distribution of the drug, so there is a need to develop an intelligent drug delivery system to realize precise treatment. In this work, tofacitib, gallic acid, targeted molecule folic acid, and Fe(III) were selected to assemble a novel type of artificial controllable nanodrug GF-TF. The self-photoacoustic/magnetic resonance imaging (self-PA/MRI) monitored the enrichment of GF-TF in the lesion in real-time, and artificially regulated the addition of deferoxamine (DFO) at the optimal enrichment. DFO strongly chelates Fe(III) in GF-TF and causes its structure to disintegrate gradually, and the self-PA/MRI signal of GF-TF became weaker while tofacitib began to be released, thus realizing the precise and artificially controlled release of the drug under the guidance of imaging. This nanodrug not only achieves efficient aggregation of drugs in inflamed joints, but also achieves real-time monitoring and precise control of drug release through self-PA/MRI, providing a new strategy for the precise treatment of RA.

Predictive power of different Akkermansia phylogroups in clinical response to PD-1 blockade against non-small cell lung cancer.

Immune checkpoint blockade has emerged as a promising form of cancer therapy. However, only some patients respond to checkpoint inhibitors, while a significant proportion of patients do not, calling for the discovery of reliable biomarkers. Recent studies reported the importance of the gut microbiome in the clinical response to PD-1 blockade against advanced non-small cell lung cancer (NSCLC), highlighting Akkermansia muciniphila as a candidate biomarker. Motivated by the genomic and phenotypic differences across Akkermansia muciniphila strains and Akkermansia (Akk) phylogroups (AmIa, AmIb, AmII, AmIII and AmIV), we analyzed fecal metagenomic sequencing data from three publicly available NSCLC cohorts (n=425). Encouragingly, we found that patients' responses to PD-1 blockade are significantly different across different Akk phylogroups, highlighting the relatively stronger association between AmIa and positive response than the other phylogroups. We built a machine learning model based on Akk gene profiles, which improved the predictive power and shed light on a group of Akk genes that may be associated with the response to PD-1 blockade. In summary, our study underlines the benefits of high-resolution analysis of Akk genomes in the search for biomarkers that may improve the prediction of patients' responses to cancer immunotherapy.

A study at the wildlife-livestock interface unveils the potential of feral swine as a reservoir for extended-spectrum ß-lactamase-producing Escherichia coli.

Wildlife is known to serve as carriers and sources of antimicrobial resistance (AMR). Due to their unrestricted movements and behaviors, they can spread antimicrobial resistant bacteria among livestock, humans, and the environment, thereby accelerating the dissemination of AMR. Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae is one of major concerns threatening human and animal health, yet transmission mechanisms at the wildlife-livestock interface are not well understood. Here, we investigated the mechanisms of ESBL-producing bacteria spreading across various hosts, including cattle, feral swine, and coyotes in the same habitat range, as well as from environmental samples over a two-year period. We report a notable prevalence and clonal dissemination of ESBL-producing E. coli in feral swine and coyotes, suggesting their persistence and adaptation within wildlife hosts. In addition, in silico studies showed that horizontal gene transfer, mediated by conjugative plasmids and insertion sequences elements, may play a key role in spreading the ESBL genes among these bacteria. Furthermore, the shared gut resistome of cattle and feral swine suggests the dissemination of antibiotic resistance genes at the wildlife-livestock interface. Taken together, our results suggest that feral swine may serve as a reservoir of ESBL-producing E. coli.

Swine Gastrointestinal Microbiota and the Effects of Dietary Amino Acids on Its Composition and Metabolism.

Many researchers consider gut microbiota (trillions of microorganisms) an endogenous organ of its animal host, which confers a vast genetic diversity in providing the host with essential biological functions. Particularly, the gut microbiota regulates not only gut tissue structure but also gut health and gut functionality. This paper first summarized those common bacterial species (dominated by the Firmicutes, Bacteroidota, and Proteobacteria phyla) in swine gut and then briefly discussed their roles in swine nutrition and health, which include roles in nutrient metabolism, pathogen exclusion, and immunity modulation. Secondly, the current knowledge on how dietary nutrients and feed additives affect the gut bacterial composition and nutrient metabolism in pigs was discussed. Finally, how dietary amino acids affect the relative abundances and metabolism of bacteria in the swine gut was reviewed. Tryptophan supplementation promotes the growth of beneficial bacteria and suppresses pathogens, while arginine metabolism affects nitrogen recycling, impacting gut immune response and health. Glutamate and glutamine supplementations elevate the levels of beneficial bacteria and mitigate pathogenic ones. It was concluded that nutritional strategies to manipulate gut microbial ecosystems are useful measures to optimize gut health and gut functions. For example, providing pigs with nutrients that promote the growth of Lactobacillus and Bifidobacterium can lead to better gut health and growth performance, especially when dietary protein is limited. Further research to establish the mechanistic cause-and-effect relationships between amino acids and the dynamics of gut microbiota will allow swine producers to reap the greatest return on their feed investment.

Spinal microRNA-134-5p targets glutamate receptor ionotropic kainate 3 to modulate opioid induced hyperalgesia in mice.

Background: Fentanyl and its analogs are extensively used for pain relief. However, their paradoxically pronociceptive effects often lead to increased opioids consumption and risk of chronic pain. Compared to other synthetic opioids, remifentanil has been strongly linked to acute opioid hyperalgesia after exposure [remifentanil-induced hyperalgesia (RIH)]. The epigenetic regulation of microRNAs (miRNAs) on targeted mRNAs has emerged as an important pathogenesis in pain. The current research aimed at exploring the significance and contributions of miR-134-5p to the development of RIH. Methods: Both the antinociceptive and pronociceptive effects of two commonly used opioids were assessed, and miRNA expression profiles in the spinal dorsal horn (SDH) of mice acutely exposed to remifentanil and remifentanil equianalgesic dose (RED) sufentanil were screened. Next, the candidate miRNA level, cellular distribution, and function were examined by qPCR, fluorescent in situ hybridization (FISH) and Argonaute-2 immunoprecipitation. Furthermore, bioinformatics analysis, luciferase assays, miRNA overexpression, behavioral tests, golgi staining, electron microscopy, whole-cell patch-clamp recording, and immunoblotting were employed to investigate the potential targets and mechanisms underlying RIH. Results: Remifentanil induced significant pronociceptive effects and a distinct miRNA-profile from sufentanil when compared to saline controls. Among top 30 differentially expressed miRNAs spectrum, spinal miR-134-5p was dramatically downregulated in RIH mice but remained comparative in mice subjected to sufentanil. Moreover, Glutamate Receptor Ionotropic Kainate 3 (Grik3) was a target of miR-134-5p. The overexpression of miR-134-5p attenuated the hyperalgesic phenotype, excessive dendritic spine remodeling, excitatory synaptic structural plasticity, and Kainate receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in SDH resulting from remifentanil exposure. Besides, intrathecal injection of selective KA-R antagonist was able to reverse the GRIK3 membrane trafficking and relieved RIH. Conclusion: The miR-134-5p contributes to remifentanil-induced pronociceptive features via directly targeting Grik3 to modulate dendritic spine morphology and synaptic plasticity in spinal neurons.

Transmission of antibiotic resistance at the wildlife-livestock interface.

Antibiotic-resistant microorganisms (ARMs) are widespread in natural environments, animals (wildlife and livestock), and humans, which has reduced our capacity to control life threatening infectious disease. Yet, little is known about their transmission pathways, especially at the wildlife-livestock interface. This study investigated the potential transmission of ARMs and antibiotic resistance genes (ARGs) between cattle and wildlife by comparing gut microbiota and ARG profiles of feral swine (Sus scrofa), coyotes (Canis latrans), cattle (Bos taurus), and environmental microbiota. Unexpectedly, wild animals harbored more abundant ARMs and ARGs compared to grazing cattle. Gut microbiota of cattle was significantly more similar to that of feral swine captured within the cattle grazing area where the home range of both species overlapped substantially. In addition, ARMs against medically important antibiotics were more prevalent in wildlife than grazing cattle, suggesting that wildlife could be a source of ARMs colonization in livestock.

Tracing the source and route of uterine colonization by exploring the genetic relationship of Escherichia coli isolated from the reproductive and gastrointestinal tract of dairy cows.

The source and route of bacterial colonization of the uterus are still not established. The objective was to investigate the source and route of bacterial colonization of the uterus by exploring the genetic relationship among E. coli strains isolated from the gastrointestinal and the reproductive tract of dairy cows pre- and postpartum. Secondarily, uterine health status (metritis vs. healthy) was evaluated. Cows (n = 34) had the rectoanal junction (RAJ), vulva, and vagina swabbed every three days starting six days before expected calving until nine days postpartum. The uterus was swabbed postpartum. A blood sample was collected at all time points, but cultures were negative. Whole-genome sequencing was performed on 44 isolates recovered from eight cows (four metritic and four healthy) with growth on selective E. coli media from the RAJ, vulva and/or vagina and uterus. Clonal isolates were found in the RAJ or the vulva prepartum and in the vulva, vagina or uterus postpartum. Clonal isolates were also found in the RAJ, the vulva, the vagina and the uterus postpartum. Clonal isolates were found in individual cows and different cows. Absence of clustering based on virulence factor genes and all genes indicate no strain specificity to body site or uterine health status. These findings indicate that the gastrointestinal tract is the likely source of bacteria that colonize the reproductive tract via ascending colonization of the uterus through the lower genital tract. Additionally, cow to cow transmission occurs, and strains are not specific to body site or to health status.

A novel combination therapy for multidrug resistant pathogens using chitosan nanoparticles loaded with ß-lactam antibiotics and ß-lactamase inhibitors.

Antimicrobial resistance is one of the greatest global threats. Particularly, multidrug resistant extended-spectrum ß-lactamase (ESBL)-producing pathogens confer resistance to many commonly used medically important antibiotics, especially beta-lactam antibiotics. Here, we developed an innovative combination approach to therapy for multidrug resistant pathogens by encapsulating cephalosporin antibiotics and ß-lactamase inhibitors with chitosan nanoparticles (CNAIs). The four combinations of CNAIs including two cephalosporin antibiotics (cefotaxime and ceftiofur) with two ß-lactamase inhibitors (tazobactam and clavulanate) were engineered as water-oil-water emulsions. Four combinations of CNAIs showed efficient antimicrobial activity against multidrug resistant ESBL-producing Enterobacteriaceae. The CNAIs showed enhanced antimicrobial activity compared to naïve chitosan nanoparticles and to the combination of cephalosporin antibiotics and ß-lactamase inhibitors. Furthermore, CNAIs attached on the bacterial surface changed the permeability to the outer membrane, resulting in cell damage that leads to cell death. Taken together, CNAIs have provided promising potential for treatment of diseases caused by critically important ESBL-producing multidrug resistant pathogens.

The Gut Microbiota of Newborn Calves and Influence of Potential Probiotics on Reducing Diarrheic Disease by Inhibition of Pathogen Colonization.

Calf diarrhea is one of the most concerning challenges facing both the dairy and beef cattle industry. Maintaining healthy gut microbiota is essential for preventing gastrointestinal disorders. Here, we observed significantly less bacterial richness in the abnormal feces with watery or hemorrhagic morphology compared to the normal solid feces. The normal solid feces showed high relative abundances of Osllospiraceae, Christensenellaceae, Barnesiella, and Lactobacillus, while the abnormal feces contained more bacterial taxa of Negativicutes, Tyzzerella, Parasutterella, Veillonella, Fusobacterium, and Campylobacter. Healthy calves had extensive bacterial-bacterial correlations, with negative correlation between Lactobacillus and potential diarrheagenic Escherichia coli-Shigella, but not in the abnormal feces. We isolated Lactobacillus species (L. reuteri, L. johnsonii, L. amylovorus, and L. animalis), with L. reuteri being the most abundant, from the healthy gut microbiota. Isolated Lactobacillus strains inhibited pathogenic strains including E. coli K88 and Salmonella Typhimurium. These findings indicate the importance of a diverse gut microbiota in newborn calf's health and provide multiple potential probiotics that suppress pathogen colonization in the gastrointestinal tract to prevent calf diarrhea.

Draft Genome Sequence of NDM-Encoding Klebsiella pneumoniae Isolated from Feral Swine.

New Delhi metallo-ß-lactamase (NDM)-producing Enterobacteriaceae pose a great threat to public health globally. Most known NDM-producing Enterobacteriaceae are associated with human hospital or community infections. Here, we report the draft genome sequence of an NDM-1-encoding Klebsiella pneumoniae strain isolated from feral swine (Sus scrofa) captured in Florida, USA.

Streptococcus vicugnae sp. nov., isolated from faeces of alpacas (Vicugna pacos) and cattle (Bos taurus), Streptococcus zalophi sp. nov., and Streptococcus pacificus sp. nov., isolated from respiratory tract of California sea lions (Zalophus californianus).

Four novel independent strains of Streptococcus spp. were isolated from faeces of alpaca (SL1232T), cattle (KCJ4950), and from respiratory tract of wild California sea lions (CSL7508T, CSL7591T). The strains were indole-, oxidase- and catalase-negative, non-spore-forming, non-motile Gram-positive cocci in short and long chains, facultative anaerobes. The 16S rRNA gene of SL1232T and KCJ4950 shared 99.40-99.60% nucleotide similarity to strains of S. equinus, S. lutetiensis, S. infantarius, and the 16S rRNA gene of CSL7508T and CSL7591T demonstrated 98.72 and 98.92% similarity, respectively, to S. marimammalium. All other known Streptococcus species had the 16S rRNA gene sequence similarities of ≤95%. The genomes were sequenced for the novel strains. Average nucleotide identity (ANI) analysis for strains SL1232T and KCJ4950, showed the highest similarity to S. equinus, S. lutetiensis, and S. infantarius with 85.21, 87.17, 88.47, 85.54, 87.47 and 88.89%, respectively, and strains CSL7508T and CSL7591T to S. marimammalium with 87.16 and 83.97%, respectively. Results of ANI were confirmed by pairwise digital DNA-DNA hybridization and phylogeny, which also revealed that the strains belong to three novel species of the genus Streptococcus. Phenotypical features of the novel species were in congruence with closely related members of the genus Streptococcus and gave negative reactions with the tested Lancefield serological groups (A-D, F and G). MALDI-TOF mass spectrometry supported identification of the species. Based on these data, we propose three novel species of the genus Streptococcus, for which the name Streptococcus vicugnae sp. nov. is proposed with the type strain SL1232T (=NCTC 14341T=DSM 110741T=CCUG 74371T), Streptococcus zalophi sp. nov. is proposed with the type strain CSL7508T (=NCTC 14410T=DSM 110742T=CCUG 74374T) and Streptococcus pacificus sp. nov. is proposed with the type strain CSL7591T (=NCTC 14455T=DSM 111148T=CCUG 74655T). The genome G+C content is 36.89, 34.85, and 35.34 % and draft genome sizes are 1906993, 1581094 and 1656080 bp for strains SL1232T, CSL7508T, and CSL7591T, respectively.

Host genetics exerts lifelong effects upon hindgut microbiota and its association with bovine growth and immunity.

The gut microbiota is a complex ecological community that plays multiple critical roles within a host. Known intrinsic and extrinsic factors affect gut microbiota structure, but the influence of host genetics is understudied. To investigate the role of host genetics upon the gut microbiota structure, we performed a longitudinal study in which we evaluated the hindgut microbiota and its association with animal growth and immunity across life. We evaluated three different growth stages in an Angus-Brahman multibreed population with a graduated spectrum of genetic variation, raised under variable environmental conditions and diets. We found the gut microbiota structure was changed significantly during growth when preweaning, and fattening calves experienced large variations in diet and environmental changes. However, regardless of the growth stage, we found gut microbiota is significantly influenced by breed composition throughout life. Host genetics explained the relative abundances of 52.2%, 40.0%, and 37.3% of core bacterial taxa at the genus level in preweaning, postweaning, and fattening calves, respectively. Sutterella, Oscillospira, and Roseburia were consistently associated with breed composition at these three growth stages. Especially, butyrate-producing bacteria, Roseburia and Oscillospira, were associated with nine single-nucleotide polymorphisms (SNPs) located in genes involved in the regulation of host immunity and metabolism in the hindgut. Furthermore, minor allele frequency analysis found breed-associated SNPs in the short-chain fatty acids (SCFAs) receptor genes that promote anti-inflammation and enhance intestinal epithelial barrier functions. Our findings provide evidence of dynamic and lifelong host genetic effects upon gut microbiota, regardless of growth stages. We propose that diet, environmental changes, and genetic components may explain observed variation in critical hindgut microbiota throughout life.

Diverse ß-lactam antibiotic-resistant bacteria and microbial community in milk from mastitic cows.

Intramammary bacterial infection, the most common cause of mastitis, is the most costly disease in dairy cattle in the US and reason for antibiotic usage. Ceftiofur, a third-generation cephalosporin, is generally used to treat such disease, but it has a high treatment failure rate. Though the reason is not known clearly, it is hypothesized that multiple factors are associated with the treatment failure. In this study, we analyzed 169 milk samples from cows with mastitis in two independent dairy farms (Farm A and B) in which 19.4% (Farm A) and 14.3% (Farm B) of the antibiotic treated cows were not cured. The prevalence of cephalosporin-resistant bacteria (CRB) in milk was 72.0% and 42.1% in Farm A and B, respectively. Nineteen and nine bacterial genera were identified in Farm A and B respectively, with the most abundant genus being Staphylococcus (27.1%; Farm A) and Bacillus (63.5%; Farm B). However, no strong relationship between the treatment failure rate and the CRB prevalence was observed. Furthermore, the metagenomic analysis showed no significant differences in the α- and ß-diversities of microbiota in milk samples from cured and uncured cows, suggesting that antibiotic-resistant bacteria were not the sole reason for the antibiotic treatment failure. KEY POINTS: • The mastitic milk samples had high prevalence of cephalosporin-resistant bacteria (CRB). • The CRB identified belong to diversified species. • Antibiotic treatment failure was not solely caused by the abundance of CRB.

Host genetic effects upon the early gut microbiota in a bovine model with graduated spectrum of genetic variation.

Multiple synergistic factors affect the development and composition of mammalian gut microbiota, but effects of host genetics remain unclear. To illuminate the role of host genetics on gut microbiota, we employed animals with a graduated spectrum of genetic variation with minimal environmental influences. We bred 228 calves with linearly varying breed composition from 100% Angus (Bos taurus) to 100% Brahman (Bos indicus), as a proxy for genetic variation, and then raised the offspring in the same environment with identical diets. We hypothesized each breed would harbor distinct gut microbiota due to genetic influence. We found that the gut microbiota of preweaning calves at 3 months old is significantly affected by host genetics, profoundly by paternal genome. We also demonstrate that single nucleotide polymorphisms in host mucin-encoding genes, critical for gut mucosal health, are significantly correlated with both breed composition and mucin-degrading gut bacteria. We further demonstrate host genetics indirectly changes gut microbiota composition via microbe-microbe interactions. These findings indicate a strong contribution by host genetics in shaping the gut microbiota during early life stages, shedding light on impact of animal breeding on gut microbiota, which is associated with animal growth and health.

Animal Breed Composition Is Associated With the Hindgut Microbiota Structure and ß-Lactam Resistance in the Multibreed Angus-Brahman Herd.

Antibiotics have been widely used in livestock to treat and prevent bacterial diseases. However, use of antibiotics has led to the emergence of antibiotic resistant microorganisms (ARMs) in food animals. Due to the decreased efficacy of antibiotics, alternatives to antibiotics that can reduce infectious diseases in food animals to enhance animal health and growth performance are urgently required. Here, we show that animal genetics is associated with the hindgut microbiome, which is related to fat deposition and beta-lactam resistance in the gastrointestinal tract. We investigated the hindgut microbiota structure in 95 postweaning heifers belonging to the unique multibreed Angus-Brahman herd with breed composition ranging from 100% Angus to 100% Brahman. The hindgut microbial composition of postweaning heifers differed among breed groups. The mucin-degrading bacterium Akkermansia known for promoting energy expenditure was enriched in Brahman calves that contained less intramuscular fat content, while butyrate-producing bacterium Faecalibacterium was linearly positively correlated with Angus proportion. Moreover, the higher relative abundance of beta-lactam resistant genes including ampC gene and arcA gene was associated with the greater Brahman proportion. As the first study aimed at understanding changes in hindgut microbiota among beef cattle with linear gradient of breed composition and its association with marbling in meat, our results suggest that the effects of animal genetics on the gut microbiota structure is associated with fat deposition and potentially a factor affecting the gut antimicrobial resistance.

Moderate Dietary Protein Restriction Optimized Gut Microbiota and Mucosal Barrier in Growing Pig Model.

Appropriate protein concentration is essential for animal at certain stage. This study evaluated the effects of different percentages of dietary protein restriction on intestinal health of growing pigs. Eighteen barrows were randomly assigned to a normal (18%), low (15%), and extremely low (12%) dietary protein concentration group for 30 days. Intestinal morphology and permeability, bacterial communities, expressions, and distributions of intestinal tight junction proteins, expressions of biomarkers of intestinal stem cells (ISCs) and chymous bacterial metabolites in ileum and colon were detected. The richness and diversity of bacterial community analysis with Chao and Shannon index were highest in the ileum of the 15% crude protein (CP) group. Ileal abundances of Streptococcaceae and Enterobacteriaceae decreased respectively, while beneficial Lactobacillaceae, Clostridiaceae_1, Actinomycetaceae, and Micrococcaceae increased their proportions with a protein reduction of 3 percentage points. Colonic abundances of Ruminococcaceae, Christensenellaceae, Clostridiaceae_1, Spirochaetaceae, and Bacterodales_S24-7_group declined respectively, while proportions of Lachnospiraceae, Prevotellaceae, and Veillonellaceae increased with dietary protein reduction. Concentrations of most bacterial metabolites decreased with decreasing dietary protein concentration. Ileal barrier function reflected by expressions of tight junction proteins (occludin, zo-3, claudin-3, and claudin-7) did not show significant decrease in the 15% CP group while sharply reduced in the 12% CP group compared to that in the 18% CP group. And in the 15% CP group, ileal distribution of claudin-3 mainly located in the cell membrane with complete morphological structure. In low-protein treatments, developments of intestinal villi and crypts were insufficient. The intestinal permeability reflected by serous lipopolysaccharide (LPS) kept stable in the 15% CP group while increased significantly in the 12% CP group. The expression of ISCs marked by Lgr5 slightly increased in ileum of the 15% CP group. Colonic expressions of tight junction proteins declined in extremely low protein levels. In conclusion, moderate protein restriction (15% CP) can optimize the ileal microbiota structure via strengthening beneficial microbial populations and suppressing harmful bacterial growth and altering the function of ileal tight junction proteins as well as epithelial cell proliferation.

Dietary Clostridium butyricum Induces a Phased Shift in Fecal Microbiota Structure and Increases the Acetic Acid-Producing Bacteria in a Weaned Piglet Model.

Clostridium butyricum is known as a butyrate producer and a regulator of gut health, but whether it exerts a beneficial effect as a dietary supplement via modulating the intestinal microbiota remains elusive. This study investigated the impact of C. butyricum on the fecal microbiota composition and their metabolites 14 and 28 days after weaning with 10 g/kg dietary supplementation of C. butyricum. Dynamic changes of microbial compositions showed dramatically increasing Selenomonadales and decreasing Clostridiales on days 14 and 28. Within Selenomonadales, Megasphaera became the main responder by increasing from 3.79 to 11.31%. Following the prevalence of some acetate producers ( Magasphaera) and utilizers ( Eubacterium_hallii) at the genus level and even with a significant decrease in fecal acetate on day 28, the present data suggested that C. butyricum influenced microbial metabolism by optimizing the structure of microbiota and enhancing acetate production and utilization for butyrate production.

Complete Genome Sequence of Listeria monocytogenes Strain MR310, Isolated from a Pastured-Flock Poultry Farm System.

Investigation of Listeria monocytogenes transmission from environmental sources associated with pasture-raised chickens to poultry products is needed to determine ways to prevent potential foodborne illness. Here, we report the complete genome sequence of Listeria monocytogenes MR310, one of the isolates from a pastured-flock poultry management system.

Moderate dietary protein restriction alters the composition of gut microbiota and improves ileal barrier function in adult pig model.

This study was conducted to investigate impacts of dietary protein levels on gut bacterial community and gut barrier. The intestinal microbiota of finishing pigs, fed with 16%, 13% and 10% crude protein (CP) in diets, respectively, were investigated using Illumina MiSeq sequencing. The ileal bacterial richness tended to decrease when the dietary protein concentration reduced from 16% to 10%. The proportion of Clostridium_sensu_stricto_1 in ileum significantly decreased, whereas Escherichia-Shigella increased with reduction of protein concentration. In colon, the proportion of Clostridium_sensu_stricto_1 and Turicibacter increased, while the proportion of RC9_gut_group significantly decreased with the dietary protein reduction. Notably, the proportion of Peptostreptococcaceae was higher in both ileum and colon of 13% CP group. As for metabolites, the intestinal concentrations of SCFAs and biogenic amines decreased with the dietary protein reduction. The 10% CP dietary treatment damaged ileal mucosal morphology, and decreased the expression of biomarks of intestinal cells (Lgr5 and Bmi1), whereas the expression of tight junction proteins (occludin and claudin) in 13% CP group were higher than the other two groups. In conclusion, moderate dietary protein restriction (13% CP) could alter the bacterial community and metabolites, promote colonization of beneficial bacteria in both ileum and colon, and improve gut barrier function.

Supplementation of Milky Flavors Improves the Reproductive Performance and Gut Function Using Sow Model.

This study was conducted to evaluate the effect of flavors on reproductive performance of sows and we also studied its effect on gut barrier function. Forty-eight Landrace × Yarkshire sows were randomly allotted and fed a basal diet added 0%, 0.05% or 0.10% flavor feed, respectively from parturition to day 28 of weaning. The results showed that supplementation of 0.05% or 0.10% flavors increased average daily feed intake (ADFI) of sows and average daily gain (ADG) of piglets, decreased the weight losses of sows, increased the survival ratio of weaning piglets (P < 0.05), especially shorten the post-weaning estrus interval significantly (P < 0.05). Supplementation of flavor additives tend to reduce the weight losses of sows and raise the survival ratio of piglet weaned (P > 0.05). Moreover, addition of flavors in diets reduced the intestinal permeability and enhanced digestibility of dry matter, crude protein, and energy (P < 0.05). Flavors supplementation significantly increased the level of gonadotropin releasing hormne (GnRH) of serum in sows after weaning. In conclusion, the results suggested that supplementation of dietary flavors could improve digestibility of nutrients and the reproductive performance of sows as well as the gut barrier function.