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Although high temperatures influence gut health, data on underlying mechanisms remains scant. Using a pig model, this study performed a global analysis on how chronic heat stress affects the transport and immune function of the gut through transcriptome, proteome, microbial diversity and flow cytometry. A total of 27 pigs with similar body weights were assigned into 3 groups, control (Con) group (23 °C), chronic heat stressed (HS) group (33 °C), and pair-fed (PF) group, in a controlled environment for 21 days. Our results showed that pigs in the HS group had reduced growth performance and diminished height of ileal villi (

Background Pectin is a heteropolysaccharide that acts as an intestinal immunomodulator, promoting intestinal development and regulating intestinal flora in the gut. However, the relevant mechanisms remain obscure. In this study, pigs were fed a corn-soybean meal-based diet supplemented with either 5% microcrystalline cellulose (MCC) or 5% pectin for 3 weeks, to investigate the metabolites and anti-inflammatory properties of the jejunum. Result The results showed that dietary pectin supplementation improved intestinal integrity (Claudin-1, Occludin) and inflammatory response [interleukin (IL)-10], and the expression of proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) was down-regulated in the jejunum. Moreover, pectin supplementation altered the jejunal microbiome and tryptophan-related metabolites in piglets. Pectin specifically increased the abundance of Lactococcus, Enterococcus, and the microbiota-derived metabolites (skatole (ST), 3-indoleacetic acid (IAA), 3-indolepropionic acid (IPA), 5-hydroxyindole-3-acetic acid (HIAA), and tryptamine (Tpm)), which activated the aryl hydrocarbon receptor (AhR) pathway. AhR activation modulates IL-22 and its downstream pathways. Correlation analysis revealed the potential relationship between metabolites and intestinal morphology, intestinal gene expression, and cytokine levels. Conclusion In conclusion, these results indicated that pectin inhibits the inflammatory response by enhancing the AhR-IL22-signal transducer and activator of transcription 3 signaling pathway, which is activated through tryptophan metabolites.

Early weaning stress (EWS) in piglets is associated with intestinal dysfunction. Here, utilizing a pig EWS model to mimic early-life stress (ELS) in humans, we investigated the mechanism of ELS-induced intestinal diseases through integrated multi-omics analyses of proteome, glycome, and microbiome. Our results demonstrated that EWS resulted in disrupted the ileal barrier integrity by reducing tight junction-related gene expression and interfering with cell-cell adhesion paralleled the increased proportion of pathogens such as Escherichia_Shigella and Helicobacter. Furthermore, Proteome data revealed that the accumulation of unfolded proteins and insufficient unfolded protein response (UPR) process caused by EWS led to ER stress. Data from proteome and glycome found that EWS induced aberrant mucin O-glycans, including truncated glycans, reduction in acidic glycans, and increased in fucosylated glycans. In addition, correlation test by taking fucose and inflammatory response into account suggested that enhancement of fucose expression might be a compensatory host response. Taken together, these results extend the comprehensive knowledge of the detrimental impacts and pathogenesis of EWS and help to provide intervention targets for ELS-induced intestinal diseases in the future.

Fecal microbiota transplantation (FMT) is an effective means of modulating gut microbiota for the treatment of many diseases, including Clostridioides difficile infections. The gut-spleen axis has been established, and this is involved in the development and function of the spleen. However, it is not understood whether gut microbiota can be used to improve spleen function, especially in spleens disrupted by a disease or an anti-cancer treatment. In the current investigation, we established that alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue anticancer drug busulfan-disrupted spleen vasculature and spleen function. A10-FMT improved the gene and/or protein expression of genes involved in vasculature development, increased the cell proliferation rate, enhanced the endothelial progenitor cell capability, and elevated the expression of the cell junction molecules to increase the vascularization of the spleen. This investigation found for the first time that the reestablishment of spleen vascularization restored spleen function by improving spleen immune cells and iron metabolism. These findings may be used as a strategy to minimize the side effects of anti-cancer drugs or to improve spleen vasculature-related diseases.

Multilayer cage-houses for broiler rearing have been widely used in intensive Chinese farming in the last decade. This study investigated the characteristics and influencing factors of bacterial communities in the PM2.5 of broiler cage-houses. The PM2.5 samples and environmental variables were collected inside and outside of three parallel broiler houses at the early, middle, and late rearing stages; broiler manure was also gathered simultaneously. The bacterial 16S rRNA sequencing results indicated that indoor bacterial communities were different from the outdoor atmosphere and manure. Furthermore, the variations in airborne bacterial composition and structure were highly influenced by the environmental control variables at different growth stages. The db-RDA results showed that temperature and wind speed, which were artificially modified according to managing the needs for broiler growth, were the main factors affecting the diversity of dominant taxa. Indoor airborne and manurial samples shared numerous common genera, which contained high abundances of manure-origin bacteria. Additionally, the airborne bacterial community tended to stabilize in the middle and late stages, but the population of potentially pathogenic bacteria grew gradually. Overall, this study enhances the understanding of airborne bacteria variations and highlighted the potential role of environmental control measures in intensive farming.

As pectin is widely used as a food and feed additive due to its tremendous prebiotic potentials for gut health. Yet, the underlying mechanisms associated with its protective effect remain unclear. Twenty-four piglets (Yorkshire × Landrace, 6.77 ± 0.92 kg) were randomly divided into three groups with eight replicates per treatment: (1) Control group (CON), (2) Lipopolysaccharide-challenged group (LPS), (3) Pectin-LPS group (PECL). Piglets were administrated with LPS or saline on d14 and 21 of the experiment. Piglets in each group were fed with corn-soybean meal diets containing 5% citrus pectin or 5% microcrystalline cellulose. Our result showed that pectin alleviated the morphological damage features by restoring the goblet numbers which the pig induced by LPS in the cecum. Besides, compared with the LPS group, pectin supplementation elevated the mRNA expression of tight junction protein [Claudin-1, Claudin-4, and zonula occludens-1 (ZO-1)], mucin (Muc-2), and anti-inflammatory cytokines [interleukin 10 (IL-10), and IL-22]. Whereas pectin downregulated the expression of proinflammatory cytokines (IL-1β, IL-6, IL-18), tumor necrosis factor-&alpha (TNF-α), and NF-κB. What is more, pectin supplementation also significantly increased the abundance of beneficial bacteria (Lactobacillus, Clostridium_sensu_stricto_1, Blautia, and Subdoligranulum), and significantly reduced the abundance of harmful bacteria, such as Streptococcus. Additionally, pectin restored the amount of short-chain fatty acids (SCFAs) after being decreased by LPS (mainly Acetic acid, Propionic acid, and Butyric acid) to alleviate gut injury and improve gut immunity via activating relative receptors (GPR43, GPR109, AhR). Mantel test and correlation analysis also revealed associations between intestinal microbiota and intestinal morphology, and intestinal inflammation in piglets. Taken together, dietary pectin supplementation enhances the gut barrier and improves immunity to ameliorate LPS-induced injury by optimizing gut microbiota and their metabolites.

Dihydroquercetin (DHQ) is a natural flavonoid with multiple bioactivities, including hepatoprotective effects. This study aimed to investigate whether DHQ improved lipid dysmetabolism in the body, especially in the liver, and whether there is a relationship between hepatic metabolism and altered gut flora in high-fat diet (HFD)-induced mice. HFD-induced mice were given 50 mg/kg body weight DHQ intragastrically for 10 weeks. The data showed that DHQ reduced body weight, the weight of the liver and white adipose tissue as well as serum leptin, LPS, triglyceride and cholesterol levels. RNA-seq results indicated that DHQ down-regulated lipogenesis-related genes and up-regulated fatty acid oxidation-related genes, including MOGAT1 and CPT1A. Furthermore, DHQ had a tendency to decrease hepatic cholesterol contents by reducing the mRNA levels of cholesterol synthesis genes such as FDPS and HMGCS1. 16S rRNA sequencing analysis indicated that DHQ significantly decreased the richness of Lactococcus, Lachnoclostridium, and Eubacterium_xylanophilum_group. Correlation analysis further demonstrated that these bacteria, Lactococcus and Eubacterium_xylanophilum_group in particular, had significantly positive correlation with lipid and cholesterol synthesis genes, and negative correlation with fatty acid oxidation genes. In conclusion, DHQ could improve hepatic lipid dysmetabolism potentially by improved gut microbial community, which may be used as an intervention strategy in hepatic metabolism diseases.

Glycerol was generally added to the inoculum as a cryoprotectant. However, it was also a suitable substrate for microbial fermentation, which may produce more SCFAs, thereby decreased pH of the fermentation broth. This study investigated the effect of supplementing glycerol to inoculum on in vitro fermentation and whether an enhanced buffer capacity of medium could maintain the pH stability during in vitro batch fermentation, subsequently improving the accuracy of short chain fatty acids (SCFAs) determination, especially propionate. Two ileal digesta were fermented by pig fecal inoculum with or without glycerol (served as anti-frozen inoculum or frozen inoculum) in standard buffer or enhanced buffer solution (served as normal or modified medium). Along with the fermentation, adding glycerol decreased the pH of fermentation broth (p < 0.05). However, modified medium could alleviate the pH decrement compared with normal medium (p < 0.05). The concentration of total propionic acid production was much higher than that of other SCFAs in anti-frozen inoculum fermentation at 24 and 36 h, thereby increasing the variation (SD) of net production of propionate. The α-diversity analysis showed that adding glycerol decreased Chao1 and Shannon index under normal medium fermentation (p < 0.05) compared to modified medium (p < 0.05) along with fermentation. PCoA showed that all groups were clustered differently (p < 0.01). Adding glycerol improved the relative abundances of Firmicutes, Anaerovibrio, unclassified_f_Selenomonadaceae, and decreased the relative abundance of Proteobacteria (p < 0.05). The relative abundances of Firmicutes, such as Lactobacillus, Blautia and Eubacterium_Ruminantium_group in modified medium with frozen inoculum fermentation were higher than (p < 0.05) those in normal medium at 36 h of incubation. These results showed that adding glycerol in inoculum changed the fermentation patterns, regardless of substrate and medium, and suggested fermentation using frozen inoculum with modified medium could maintain stability of pH, improve the accuracy of SCFA determination, as well as maintain a balanced microbial community.

Young type 2 diabetes (T2D) affects 15% of the population, with a noted increase in cases, and T2D-related male infertility has become a serious issue in recent years. The current study aimed to explore the improvements of alginate oligosaccharide (AOS)-modified gut microbiota on semen quality in T2D. The T2D was established in young mice of 5 weeks of age with a blood glucose level of 21.2 ± 2.2 mmol/L, while blood glucose was 8.7 ± 1.1 mM in control animals. We discovered that fecal microbiota transplantation (FMT) of AOS-improved microbiota (A10-FMT) significantly decreased blood glucose, while FMT of gut microbiota from control animals (Con-FMT) did not. Sperm concentration and motility were decreased in T2D to 10% to 20% of those in the control group, while A10-FMT brought about a recovery of around 5- to 10-fold. A10-FMT significantly increased small intestinal

This study aimed to investigate the effects of different feeding patterns on meat quality, gut microbiota and its metabolites of Tibetan pigs. Tibetan pigs with similar body weight were fed the high energy diets (HEP, 20 pigs) and the regular diets (RFP, 20 pigs), and free-ranging Tibetan pigs (FRP, 20 pigs) were selected as the reference. After 6 weeks of experiment, meat quality indexes of semitendinosus muscle (SM) and cecal microbiota were measured. The results of meat quality demonstrated that the shear force of pig SM in FRP group was higher than that in HEP and RFP groups (p p p L* value) of FRP pigs increased compared with RFP and HEP groups (p a* value) of FRP pigs was higher than that of RFP group (p FA) profile exhibited that the total FAs and unsaturated FAs of pig SM in HEP and RFP groups were higher than those in FRP group (p PUFAs) and lower n-6/n-3 PUFA ratio than HEP pigs (p p p Alistipes, Anaerovibrio, Acetitomaculun, etc., were identified under different feeding patterns (p Prevotellaceae_NK3B31_group, Prevotellaceae UCG-003 and Christensenellaceae_R-7_group (p

Tibetan pigs were thought to have good performances of rough feeding tolerance, which may be related to the gut microbiota. This study was conducted to investigate the changes of colonic microbiota contribute to fiber utilization in Tibetan pigs fed alfalfa supplementation diet compared with basal diet, and verified whether the microbial community in Tibetan pigs fed alfalfa diet was beneficial to utilize fiber using in vitro fermentation. A total of 40 Tibetan pigs were allocated into two groups and fed with a corn-soybean meal basal diet (CD) or a 50% alfalfa supplementation diet (AD) for 42d. Our results showed pigs fed CD diet improved carcass weight compared to pigs fed AD diet (p p Streptococcus) abundance (FDR UCG-005, Rikenellaceae_RC9_gut_group, Prevotellaceae_UCG-003, Alloprevotella, Marvinbryantia, and Anaerovibrio) in the colonic digesta (FDR p in vitro fermentation. Collectively, our results indicated that alfalfa supplementation in diets improved the abundance of fiber-degrading bacteria and SCFA production in the hindgut of Tibetan pig, as well as enhanced the fermentation capacity of fecal microbiota.

This study aimed to investigate the effects of chronic heat stress on the immunophenotyping of lymphocytes in immune organs of growing pigs. A single-factor randomized block design was used, and 15 healthy growing large white barrows (5 litters, 3 pigs/litter) with similar body weight (40.8 kg) were assigned into 3 groups (5 pigs in each group). Groups were: control group (Con, in 23 °C environmental control chamber, fed ad libitum), heat stress group (HS, in 33 °C environmental control chamber, fed ad libitum), and pair-fed group (PF, in 23 °C environmental control chamber, fed diets according to the feed intake of HS group). After a 7-d adaption, the experiment lasted for 21 d. The results showed as follows: (1) activated T cells in the thymus of HS pigs were higher than those in PF pigs (P0.05). Monocytes and dendritic cells in the thymus of HS pigs were significantly higher than that in Con and PF pigs (P0.05), while the proportions of these 2 lymphocytes in the thymus of Con pigs did not differ from PF pigs (P0.05). Compared with Con pigs, the proportion of CD4+ (P0.05) and CD8+ T cells (P0.10) in the thymus was increased in HS pigs, while the proportion of CD4+ and CD8+ T cells in PF pigs did not differ from Con pigs (P0.05). (2) Compared with Con pigs, significantly decreased T cells, increased B cells and monocytes were found in the spleen of pigs exposed to heat stress (P0.05); the proportions of these 3 types of lymphocytes were not significantly different between Con and PF pigs (P0.05). The proportions of CD4+ T cells and Treg cells in the spleen of pigs exposed to heat stress tended to be lower than those in the Con pigs (P0.10). (3) The proportion of lymphocytes in the tonsils of pigs exposed to heat stress did not differ from Con pigs (P0.05); compared with PF pigs, the proportion of Treg cells was significantly decreased in HS pigs (P0.05). In conclusion, chronic heat stress stimulates the development and maturation of T cells in the pig thymus toward CD4+ and CD8+ T cells and increases the proportion of monocytes and dendritic cells; under the condition of chronic heat stress, the immune response process in the spleen of pigs is enhanced, but chronic heat stress impairs the survival of CD4+ T cells in the spleen.Chronic heat stress (HS) has become a common hazard to livestock and poultry as global warming intensifies and breeding densities increase, which undoubtedly causes enormous economic losses to animal husbandry annually. Furthermore, it could also negatively impact the immune function of poultry and vaccines, resulting in various animal diseases. Until now, very few studies have focused on how HS affects the immune system of growing pigs, especially the immunophenotyping of lymphocytes in their immune organs (thymus, spleen and tonsils). In this study, the spleen and thymus are more severely affected by chronic HS than tonsils in growing pigs. Chronic HS stimulates the development and maturation of CD4+ and CD8+ T lymphocytes in the thymus. Under chronic HS, the immune response process in the spleen is enhanced, that is, the proportion of monocytes and B lymphocytes supporting immune responses increased, while the proportion of Treg cells decreased; yet long-term HS damaged the survival of CD4+ T lymphocytes in spleen.

In recent years, the three-way crossbred commercial pigs are extensively cultured in Tibet. However, there have been few studies about the effect of high-altitude hypoxic environment on intestinal health of them. Therefore, we selected Tibetan pigs (TP) and the three-way crossbred commercial pigs (CP-H) living in the Tibet (3,500–3,700 m in altitude) as a positive control group and treatment group, respectively. The three-way crossbred commercial pigs (CP-L) living at altitudes 800–1,000 m sea level were selected as a negative control group. The colonic chyme, colonic mucosa, colonic tissue and serum samples were collected for the detection of gut microbiota and intestinal inflammation. The results showed that high-altitude hypoxic environment promoted the occurrence of colonic inflammation, disrupted the colonic barrier to some extent. And Hematoxylin–Eosin (HE) staining revealed that mild inflammatory cell infiltration was observed in colon of CP-H. 16S rRNA gene sequencing revealed that the microbial community composition of CP-H was changed compared with CP-L. Gut bacterial communities formed distinctly different clusters in principal coordinates analysis (PCoA) space, and Chao 1 index of CP-H was also decreased. At the genus level, Terrisporobacter showed greater enrichment in the CP-H than lower-altitude pigs. Colstridium-sensu-stricto-1 showed lower enrichment in the CP-H than lower-altitude pigs. However, the concentration of valeric acid in colonic chyme of CP-H was higher than CP-L and TP. Correlation analysis indicated that Terrisporobacter was positively associated with the relative mRNA expression level of IL-1β and the content of lipopolysaccharide (LPS), and was negatively correlated with the relative mRNA expression level of IL-10. The Streptococcus was positively associated with the concentrations of valerate. In summary, high-altitude hypoxic environment changed compositions of gut microbiota, promoted the occurrence of colonic inflammation, and disrupted intestinal barrier of the three-way crossbred commercial pigs.

Human sperm concentration and motility have dropped dramatically (50%) in the past few decades, and environmental factors are involved in this decline. Long non-coding RNAs (lncRNA) have been discovered to be involved in many cellular processes including spermatogenesis.This investigation aimed to explore the role of lncRNA8276 in murine spermatogenesis.The expression of lncRNA8276 was modified by knockdown or overexpression in mouse testes and spermatogonial stem cells (C18-4 cell line). Sperm quality was determined in the F0 and F1 generations of mice. Furthermore, the underlying mechanisms were studied through gene expression and/or protein expression of spermatogenesis-related genes and cell junction-related genes by different methods.In the current investigation, we discovered that sperm lncRNA8276 was decreased by NHOur study suggests that lncRNA8276 may be involved in cell-cell junction formation in the mouse testis to regulate spermatogenesis. It may be a target for the modification of spermatogenesis and male fertility, or male contraception. This investigation offers a potential therapeutic strategy for male infertility.

Alginate oligosaccharides (AOS), natural polymers from brown seaweeds (such as Laminaria japonica, Undaria pinnatifida, and Sargassum fusiforme), have been reported to possess many beneficial advantages for health. In the current study, after 9 weeks of dietary supplementation, AOS 10 mg/kg group (AOS 10) group increased boar sperm motility from 87.8% to 93.5%, p Bifidobacterium, Coprococcus, Butyricicoccus (1.3–2.3-fold; p p p p

Taxifolin (TAX), as a natural flavonoid, has been widely focused on due to its strong anti-oxidation, anti-inflammation, anti-virus, and even anti-tumor activity. However, the effect of TAX on semen quality was unknown. The purpose of this study was to analyze the beneficial influences of adding feed additive TAX to boar semen in terms of its quality and potential mechanisms. We discovered that TAX increased sperm motility significantly in Duroc boars by the elevation of the protein levels such as ZAG, PKA, CatSper, and p-ERK for sperm quality. TAX increased the blood concentration of testosterone derivatives, antioxidants such as melatonin and betaine, unsaturated fatty acids such as DHA, and beneficial amino acids such as proline. Conversely, TAX decreased 10 different kinds of bile acids in the plasma. Moreover, TAX increased “beneficial” microbes such as Intestinimonas, Coprococcus, Butyrivibrio, and Clostridium_XlVa at the Genus level. However, TAX reduced the “harmful” intestinal bacteria such as Prevotella, Howardella, Mogibacterium, and Enterococcus. There was a very close correlation between fecal microbes, plasma metabolites, and semen parameters by the spearman correlation analysis. Therefore, the data suggest that TAX increases the semen quality of Duroc boars by benefiting the gut microbes and blood metabolites. It is supposed that TAX could be used as a kind of feed additive to increase the semen quality of boars to enhance production performance.

The effects of multi-enzymes mixture supplementation or combination with inactivated Lactobacillus on growth performance, intestinal barrier, and cecal microbiota were investigated in broilers at the age of 15–42 days fed a wheat-based diet. A total of 576 broilers (12 broilers/cage; n = 12) were used and divided into four groups and randomly allotted to four experimental diets throughout grower (15–28 days of age) and finisher (29–42 days of age) phases. Diets consisted of a corn-soybean meal-based diet (BD), a wheat-soybean meal-based diet (WD), and WD supplemented multi-enzymes (WED) or combined with inactivated Lactobacillus (WEPD). The results showed that the average daily gain (ADG) and body weight (BW) were reduced in broilers fed WD diet compared with those fed BD diet during the grower period (P < 0.05). Broilers in the WED or WEPD group had higher ADG and BW during the grower period (P < 0.05) and had a lower feed-to-gain ratio (F/G) compared to broilers in the WD group during the grower and overall periods (P < 0.05). Improved expression of intestinal barrier genes (claudin-1, ZO-1, and mucin-2) was observed in WEPD compared to the BD or WD group (P < 0.05). Compared to the BD group, the WD group decreased the abundance of Oscillospira, norank_f__Erysipelotrichaceae, and Peptococcus, which are related to anti-inflammatory function and BW gain. The WD also increased Bifidobacterium and some short-chain fatty acid (SCFA)-producing bacteria (Anaerotruncus, Blautia, and Oscillibacter), and Barnesiella, which were presumed as “harmful microbes” [false discovery rate (FDR) < 0.05]. WED and WEPD groups, respectively, improved Bilophila and Eubacterium_hallii_group compared with those in the WD group (FDR < 0.05). In addition, the Enterococcus abundance was reduced in the WEPD group compared to the WD group (FDR < 0.05). Higher acetate and total SCFA concentrations were observed (P < 0.05) among broilers who received a WD diet. Compared with the WD group, the WED or WEPD group further increased cecal propionate content (P < 0.05) and tended to improve butyrate concentration. These results suggested that supplemental multi-enzymes alone and combined with inactivated Lactobacillus could improve the growth performance based on the wheat-based diet and offer additional protective effects on the intestinal barrier function of broilers.

Dysregulated lipid metabolism is a key pathology in metabolic diseases and the liver is a critical organ for lipid metabolism. The gut microbiota has been shown to regulate hepatic lipid metabolism in the host. However, the underlying mechanism by which the gut microbiota influences hepatic lipid metabolism has not been elucidated. Here, a gut microbiota depletion mouse model was constructed with an antibiotics cocktail (Abx) to study the mechanism through which intestinal microbiota regulates hepatic lipid metabolism in high-fat diet (HFD)-fed mice. Our results showed that the Abx treatment effectively eradicated the gut microbiota in these mice. Microbiota depletion reduced the body weight and fat deposition both in white adipose tissue and liver. In addition, microbiota depletion reduced serum levels of glucose, total cholesterol (TC), low-density lipoproteins (LDL), insulin, and leptin in HFD-fed mice. Importantly, the depletion of gut microbiota in HFD-fed mice inhibited excessive hepatic lipid accumulation. Mechanistically, RNA-seq results revealed that gut microbiota depletion changed the expression of hepatic genes involved in cholesterol and fatty acid metabolism, such as Cd36, Mogat1, Cyp39a1, Abcc3, and Gpat3. Moreover, gut microbiota depletion reduced the abundance of bacteria associated with abnormal metabolism and inflammation, including Lachnospiraceae, Coriobacteriaceae_UCG-002, Enterorhabdus, Faecalibaculum, and Desulfovibrio. Correlation analysis showed that there was strong association between the altered gut microbiota abundance and the serum cholesterol level. This study indicates that gut microbiota ameliorates HFD-induced hepatic lipid metabolic dysfunction, which might be associated with genes participating in cholesterol and fatty acid metabolism in the liver.

Although, the cecum plays vital roles in absorption of water, electrolytes, and other small molecules, and harbors trillions of commensal bacteria to shape large intestine immune functions, it is unknown the cecum development potentials at single cell level during the very crucial neonatal developmental period. Using singe cell RNA-seq and proteomics, we have characterized six major types of cecal cells: undifferentiated cells; immune cells (Ims); cecumocytes (CCs); goblet, Paneth like cells (PLCs), and enteroendocrine cells (EECs) with specific markers. CCs mature with a gradual decrease in proportion of cells; however, Ims develop with a continuing increase in proportion of cells. Meanwhile, goblet and EEC cells reduced in proportion of cells from do to d14 or d21; PLCs increased in proportion of cells from d0 to d7 then decreased at d14 and d21. The cells exhibit specific development and maturation trends controlled by transcriptional factors, ligand-receptor pairs, and other factors. As piglets grow, cecal content and mucosal microbial diversity increases dramatically with population of beneficial microbiota, such as lactobacillus. Moreover, cecal mucosal-associated and cecal content microbiota are positively correlated and both show significant correlation with different types of cecal cells and plasma metabolites. This is the first presentation of neonatal cecal cell development and maturation naturally at single cell level with transcript, protein, microbiota and metabolism perspectives. Furthermore, this study provides an important tool for the determination of novel interventions in cecal drug delivery and metabolism studies.

High-fat diet (HFD)-induced obesity is known to be associated with reduced male fertility and decreased semen quality in humans. HFD-related male infertility is a growing issue worldwide, and it is crucial to overcome this problem to ameliorate the distress of infertile couples. For the first time, we discovered that fecal microbiota transplantation (FMT) of alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) ameliorated HFD-decreased semen quality (sperm concentration: 286.1 ± 14.1 versus 217.9 ± 17.4 million/mL; sperm motility: 40.1 ± 0.7% versus 29.0 ± 0.9%), and male fertility (pregnancy rate: 87.4 ± 1.1% versus 70.2 ± 6.1%) by benefiting blood and testicular metabolome. A10-FMT improved HFD-disturbed gut microbiota by increasing gut

This study was conducted to investigate the antioxidant effects of hydroxytyrosol (HT) administration in diquat (DQ)-challenged mice. The results showed that HT treatment markedly alleviated DQ-induced oxidative stress, which was indicated by the enhanced total antioxidant capacity (T-AOC), increased activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and decreased malondialdehyde (MDA) concentration in serum. Additionally, HT increased the mRNA expression levels of NF-E2-related factor 2 (Nrf2) and its downstream genes, including NADPH quinone oxidoreductase 1 (NQO1) and CAT in the small intestine of DQ-challenged mice. 16S rRNA gene sequencing results showed that HT treatment increased the relative abundance of Firmicutes and Lactobacillus and decreased the relative abundance of Bacteroidetes. Interestingly, Pearson correlation analysis showed that there were strong association between colonic Firmicutes, Lactobacillus, and Bacteroidetes and the activities of serum antioxidant enzymes. Meanwhile, HT significantly enhanced the colonic butyrate concentration in DQ-challenged mice. Additionally, HT treatment decreased the serum metabolites involving in glycerophospholipid metabolism, pentose and glucuronate interconversions, which were associated with alleviated oxidative stress. These results indicate that oral administration of 100 mg/kg body weight HT alleviates oxidative stress in DQ-challenged mice, which may involve Nrf2 signaling pathways via modulation of colonic microbiota.

The purpose of the current study was to investigate the effect of dietary dihydroquercetin (DHQ) supplementation on dextran sodium sulfate (DSS)-induced colitis in mice. Mice were given DHQ supplementation (3 g kg−1) throughout the study, starting 14 days prior to DSS treatment for 1 week followed by 2 days without DSS. The results showed that dietary DHQ supplementation restored DSS-induced disease activity index (DAI), colon length and histopathology scores of the colon tissue. Additionally, supplementation with DHQ reduced the pro-inflammatory cytokine levels, and enhanced the level of IL-10 in the serum. qPCR results indicated that DHQ supplementation significantly downregulated IL-1β, IL-6, and TNF-α, and upregulated IL-10 gene mRNA expression. Western blot results proved that DHQ supplementation upregulated ZO-1 and occludin levels. Using amplicon sequencing technology, 16S rRNA sequencing results showed that DHQ supplementation increased the fecal Firmicutes/Bacteroidetes ratio and the relative abundance of Lactobacillus and Dubosiella, and decreased the relative abundance of Bacteroidetes. Additionally, DHQ supplementation restored the decreased fecal acetic acid and butyric acid concentrations in DSS-induced colitis mice. Besides, Spearman's correlation analysis showed that Dubosiella was positively correlated with the butyric acid level and Bacteroidetes was positively correlated with the mRNA expression of IL-1β and IL-6. Both Lactobacillus and Dubosiella showed a negative correlation with the mRNA expression of IL-1β, IL-6, and TNF-α, and Dubosiella was positively correlated with IL-10. In summary, it was found that DHQ supplementation alleviated DSS-induced colitis which may be potentially associated with altered fecal microbiota communities in mice.

The adverse effects of short-term megadose of antibiotics exposure on the gastrointestinal and liver tissue reactions in young children have been reported. Antibiotic-induced intestinal and liver reactions are usually unpredictable and present a poorly understood pathogenesis. It is, therefore, necessary to develop strategies for reducing the adverse effects of antibiotics. Studies on the harm and rescue measures of antibiotics from the perspective of the gut–liver system are lacking. Here, we demonstrate that lincomycin exposure reduced body weight, disrupted the composition of gut microbiota and intestinal morphology, triggered immune-mediated injury and inflammation, caused liver dysfunction, and affected lipid metabolism. However, baicalin administration attenuated the lincomycin-induced changes. Transcriptome analysis showed that baicalin improved immunity in mice, as evidenced by the decreased levels of intestinal inflammatory cytokines and expression of genes that regulate Th1, Th2, and Th17 cell differentiation, and inhibited mucin type O-glycan biosynthesis pathways. In addition, baicalin improved liver function by upregulating the expression of genes involved in bile acid secretion and lipid degradation, and downregulating genes involved in lipid synthesis in lincomycin-treated mice. Bile acids can regulate intestinal immunity and strengthen hepatoenteric circulation. In addition, baicalin also improved anti-inflammatory bacteria abundance (Blautia and Coprobacillus) and reduced pathogenic bacteria abundance (Proteobacteria, Klebsiella, and Citrobacter) in lincomycin-treated mice. Thus, baicalin can ameliorate antibiotic-induced injury and its associated complications such as liver disease.

The effects of multi-enzymes mixture supplementation or combination with inactivated

Background Clinical data suggest that male reproductive dysfunction especially infertility is a critical issue for type 1 diabetic patient (T1D) because most of them are at the reproductive age. Gut dysbiosis is involved in T1D related male infertility. However, the improved gut microbiota can be used to boost spermatogenesis and male fertility in T1D remains incompletely understood. Methods T1D was established in ICR (CD1) mice with streptozotocin. Alginate oligosaccharide (AOS) improved gut microbiota (fecal microbiota transplantation (FMT) from AOS improved gut microbiota; A10-FMT) was transplanted into the T1D mice by oral administration. Semen quality, gut microbiota, blood metabolism, liver, and spleen tissues were determined to investigate the beneficial effects of A10-FMT on spermatogenesis and underlying mechanisms. Results We found that A10-FMT significantly decreased blood glucose and glycogen, and increased semen quality in streptozotocin-induced T1D subjects. A10-FMT improved T1D-disturbed gut microbiota, especially the increase in small intestinal lactobacillus, and blood and testicular metabolome to produce n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to ameliorate spermatogenesis and semen quality. Moreover, A10-FMT can improve spleen and liver functions to strengthen the systemic environment for sperm development. FMT from gut microbiota of control animals (Con-FMT) produced some beneficial effects; however, to a smaller extent. Conclusions AOS-improved gut microbiota (specific microbes) may serve as a novel, promising therapeutic approach for the improvement of semen quality and male fertility in T1D patients via gut microbiota-testis axis.

In this study, the effects of dietary fibre and types of indigestible markers (IM) on the apparent total tract digestibility (ATTD) of gross energy (GE) and nutrients as well as IM recovery in diets fed to growing pigs were investigated. A total of 30 barrows (initial body weight 40.5 ± 1.4 kg) were allotted to five experimental diets, based on a completely randomised block design, with body weight as a blocking factor. The five diets comprised a corn-soya bean meal basal diet, and four diets in which sugar beet pulp (SBP) or defatted rice bran (DFRB) partly replaced 10% or 20% of corn, soya bean meal and soya bean oil in the basal diet. All diets were formulated to contain two types of IM, namely 0.5% chromic oxide (Cr) and 1.0% celite as the source of acid-insoluble ash (AIA). Animals were subjected to a 7-d adaptation period, and their faeces were collected over a 5-d period using the total faecal collection (TC) method. Results showed that the AIA method determined similar ATTD of GE and nutrients as the TC method. Values of dietary nutrients determined via AIA and TC methods were significantly higher than those obtained by Cr (

The purpose of this study was to investigate the effects of chemically protected sodium butyrate (CSB) on growth performance and the early development and function of small intestine in broilers as one potential substitute for antibiotics. A total of 192 one-day-old Arbor Acres male broilers were randomly assigned into three dietary treatment groups (eight replicates per treatment): the control (CON) diet; ANT diet, CON diet supplemented with the antibiotics (enramycin, 8 mg/kg and aureomycin, 100 mg/kg); CSB diet, CON diet supplemented with 1000 mg/kg CSB, respectively. The results showed that dietary CSB and antibiotics addition significantly improved the growth performance of broilers by increasing the body weight gain (BWG) and feed conversion ratio (FCR) during different stages (p < 0.05). On day 21, the supplement of CSB in diet improved the structure of small intestine (duodenum, jejunum, and ileum) in broilers by increasing the ratio of villus height to crypt depth (VH/CD) (p < 0.05) and enhanced the butyric acid (BA) (p < 0.05) and total short chain fatty acids (SCFA) concentrations of small intestine (jejunum and ileum) compared with the CON and ANT diets. Besides that, the superoxide dismutase (SOD), total antioxidant capacity (TAC) and TAC to malondialdehyde (TAC/MDA) ratio of the ileal and jejunal mucosa were significantly higher (p < 0.05) in the CSB and ANT than in the CON. In addition, the supplement of CSB in diet markedly significantly enhanced α-amylase, lipase, and trypsin activities of the ileum (p < 0.05) as compared to the ANT diet. 16S rRNA gene sequencing indicated that CSB markedly increased the microbiota diversity of ileum in broilers at 21 days of age as compared to CON and ANT (p < 0.05). Furthermore, we found that Firmicutes was the predominant phyla and Lactobacillus was the major genus in the ileum of broilers. Compared with the ANT diet, the supplement of CSB in diet increased the relative abundance of some genera microbiota (e.g., Candidatus_Arthromitus, Romboutsia) by decreasing the relative abundance of Lactobacillus. Moreover, Akkermansia in the CSB was the highest in comparison to that in the CON and ANT. In addition, Kitasatospora that belongs to the phylum Actinobacteriota was only found in ileum of broilers fed the ANT diet. In summary, the supplement of 1000 mg/kg CSB in the diet improved the growth performance by promoting early development and function of the small intestine, which is associated with the regulation of intestinal flora and reestablishment of micro-ecological balance in broilers. Thus, CSB has great potential value as one of effective substitutes for in-feed antibiotics in the broiler industry.

Semen quality is one of the most important factors for the success of artificial insemination which has been widely applied in swine industry to take the advantages of the superior genetic background and higher fertility capability of boars. Hydroxytyrosol (HT), a polyphenol, has attracted broad interest due to its strong antioxidant, anti-inflammatory, and antibacterial activities. Sperm plasma membrane contains a large proportion of polyunsaturated fatty acids which is easily impaired by oxidative stress and thus to diminish semen quality. In current investigation, we aimed to explore the effects of dietary supplementation of HT on boar semen quality and the underlying mechanisms. Dietary supplementation of HT tended to increase sperm motility and semen volume/ejaculation. And the follow-up 2 months (without HT, just basal diet), the semen volume was significantly more while the abnormal sperm was less in HT group than that in control group. HT increased the “beneficial microbes” Bifidobacterium, Lactobacillus, Eubacterium, Intestinimonas, Coprococcus, and Butyricicoccus, however, decreased the relative abundance of “harmful microbes” Streptococcus, Oscillibacter, Clostridium_sensu_stricto, Escherichia, Phascolarctobacterium, and Barnesiella. Furthermore, HT increased plamsa steroid hormones such as testosterone and its derivatives, and antioxidant molecules while decreased bile acids and the derivatives. All the data suggest that HT improves gut microbiota to benefit plasma metabolites then to enhance spermatogenesis and semen quality. HT may be used as dietary additive to enhance boar semen quality in swine industry.

Background Post-weaning diarrhea in piglets reduces growth performance and increases mortality, thereby causing serious economic losses. The intestinal epithelial cells and microbiota reciprocally regulate each other in order to maintain intestinal homeostasis and control inflammation. However, a relative paucity of research has been focused on the host-derived regulatory network that controls mucin O-glycans and thereby changes gut microbiota during diarrhea in infancy. At the development stage just after birth, the ontogeny of intestinal epithelium, immune system, and gut microbiota appear similar in piglets and human infants. Here, we investigated the changes of mucin O-glycans associated with gut microbiota using a diarrheal post-weaned piglet model. Results We found that diarrhea disrupted the colonic mucus layer and caused aberrant mucin O-glycans, including reduced acidic glycans and truncated glycans, leading to an impaired gut microenvironment. Subsequently, the onset of diarrhea, changes in microbiota and bacterial translocation, resulting in compromised epithelial barrier integrity, enhanced susceptibility to inflammation, and mild growth faltering. Furthermore, we found the activation of NLRP3 inflammasome complexes in the diarrheal piglets when compared to the healthy counterparts, triggered the release of proinflammatory cytokines IL-1β and IL-18, and diminished autophagosome formation, specifically the defective conversion of LC3A/B I into LC3A/B II and the accumulation of p62. Additionally, selective blocking of the autophagy pathway by 3-MA led to the reduction in goblet cell-specific gene transcript levels in vitro. Conclusions We observed that diarrheal piglets exhibited colonic microbiota dysbiosis and mucosal barrier dysfunction. Our data demonstrated that diarrhea resulted in the activation of inflammasomes and autophagy restriction along with aberrant mucin O-glycans including reduced acidic glycans and truncated glycans. The results suggested the mucin O-glycans-microbiota axis is likely associated with diarrheal pathogenesis. Our study provides novel insights into the pathophysiology of early-weaning-induced diarrheal disease in piglets and potentially understanding of disease mechanisms of diarrhea for human infants. Understanding the molecular pathology and pathogenesis of diarrhea is a prerequisite for the development of novel and effective therapies. Our data suggest that facilitating O-glycan elongation, modifying the microbiota, and developing specific inhibitors to some key inflammasomes could be the options for therapy of diarrhea including human infants. Graphical abstract

Colitis, a chronic inflammatory bowel disease, is characterized by bloody diarrhea and inflammation in the colon. Lonicera hypoglauca (“Shanyinhua” in Chinese) and Scutellaria baicalensis (“Huangqin” in Chinese) are two traditional Chinese medicinal plants rich in polyphenols, such as chlorogenic acid (CGA) and baicalin (BA), with the effects of anti-inflammation and antioxidation. However, it remains unknown whether extracts from L. hypoglauca and S. baicalensis (LSEs) could mitigate colonic inflammation. In the present study, ICR mice (22.23 ± 1.65 g) were allocated to three groups treated with chow diet without (CON) or with dextran sulfate sodium (DSS) (CON+DSS) in water or LSE supplementation in diet with DSS (LSE+DSS), and then inflammatory and oxidative parameters and colonic microbiota were detected. The results showed that LSE (500 mg/kg) treatment mitigated DSS-induced colitis symptoms and restored the shortened colon length, the increased disease activity index (DAI), and the damaged intestinal barrier. In serum, LSE supplementation significantly decreased levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and increased IL-10 level. Meanwhile, superoxide dismutase (SOD) and catalase (CAT) were increased, and malondialdehyde (MDA) and reactive oxygen species (ROS) levels were decreased. In the colon tissue, qPCR results showed that LSE supplementation dramatically downregulated the transcriptional expression of IL-1β, IL-6, TNF-α, and MDA and upregulated the expression of SOD1, CAT, and IL-10. Additionally, the damaged gut barriers occludin and zonula occludens-1 (ZO-1) in the CON+DSS group were enhanced with LSE supplementation. Furthermore, LSE treatment regulated the gut microbial communities with higher relative abundance of Dubosiella and Ruminococcus torques group and lower relative abundance of Bacteroides and Turicibacter. Moreover, the contents of short-chain fatty acids (SCFAs) as products of gut microbiota were also increased. Correlation analysis showed that the mRNA expression of SOD1 was negatively correlated with TNF-α (r = -0.900, P < 0.05); the mRNA expression of IL-6 (r = -0.779, P < 0.05) and TNF-α (r = -0.703, P < 0.05) had a dramatically negative correlation with Dubosiella. In conclusion, LSE supplementation could effectively ameliorate inflammation by modulating oxidative stress and gut microbiota in a colitis mouse model.

The mitochondrion is also a major site for maintaining redox homeostasis between reactive oxygen species (ROS) generation and scavenging. The quantity, quality, and functional integrity of mitochondria are crucial for regulating intracellular homeostasis and maintaining the normal physiological function of cells. The role of oxidative stress in human disease is well established, particularly in inflammatory bowel disease and gastrointestinal mucosal diseases. Oxidative stress could result from an imbalance between ROS and the antioxidative system. Mitochondria are both the main sites of production and the main target of ROS. It is a vicious cycle in which initial ROS-induced mitochondrial damage enhanced ROS production that, in turn, leads to further mitochondrial damage and eventually massive intestinal cell death. Oxidative damage can be significantly mitigated by mitophagy, which clears damaged mitochondria. In this review, we aimed to review the molecular mechanisms involved in the regulation of mitophagy and oxidative stress and their relationship in some intestinal diseases. We believe the reviews can provide new ideas and a scientific basis for researching antioxidants and preventing diseases related to oxidative damage.

BackgroundAlthough, the cecum plays vital roles in absorption of water, electrolytes, and other small molecules, and harbors trillions of commensal bacteria to shape large intestine immune functions, it is unknown the cecum development potentials at single cell level during the very crucial neonatal developmental period.ResultsUsing singe cell RNA-seq and proteomics, we have characterized six major types of cecal epithelial cells: undifferentiated cells; immune cells (Ims); cecumocytes (CCs); goblet, Paneth like cells (PLCs), and enteroendocrine cells (EECs) with specific marker genes. CCs mature with a gradual decrease in number; however, Ims develop with a continuing increase in number. Meanwhile secretory cells (goblet, PLCs, EECs) reduce in number during the neonatal developmental period. The cells exhibit specific development and maturation trends controlled by transcriptional factors, ligand-receptor pairs, and other factors. As piglets grow, cecal content and mucosal microbial diversity increases dramatically with population of beneficial microbiota, such as lactobacillus, increasing significantly. Moreover, cecal mucosal-associated and cecal content microbiota are positively correlated and both show significant correlation with different types of cecal epithelial cells and plasma metabolites. ConclusionsThis is the first presentation of neonatal cecal cell development and maturation naturally at single cell level with transcript, protein, microbiota and metabolism perspectives. Furthermore, this study provides an important tool for the determination of novel interventions in cecal drug delivery and metabolism studies.

Caffeic acid (CA) is one of the major phenolic acids of coffee with multiple biological activities. Our previous study found that 500 mg/kg of chlorogenic acid (CGA) had the potential capacity of alleviating colonic inflammation. Moreover, CGA can be degraded into caffeic acid (CA) by the gut microbiota in the colon. Therefore, we hypothesize that CA can exert protective effects on colonic inflammation. To test the hypothesis, 251 mg/kg CA was supplemented to DSS-induced colitis mice. The results showed that CA treatment recovered DSS-induced disease activity index (DAI), colon length, and histopathology scores of colon tissue. Additionally, CA treatment significantly decreased pro-inflammatory cytokines and malondialdehyde (MDA) levels and increased the level of IL-10, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in serum. qPCR results indicated that CA treatment dramatically downregulated mRNA expression of IL-1β, IL-6, and TNF-α as well as upregulated SOD1, GPX1, GPX2, CAT, and IL-10. In addition, CA supplementation significantly increased mRNA expression of Nrf-2, HO-1, and NQO1, which showed its antioxidant and anti-inflammatory capacities potentially by activating the Nrf-2/HO-1 pathway. Moreover, CA supplementation prevented gut barrier damage by enhancing Occludin gene expression. Furthermore, CA supplementation altered the gut microbiome composition by decreasing the relative abundance of Bacteroides and Turicibacter, and enhancing the relative abundance of Alistipes and Dubosiella. Meanwhile, CA supplementation increases the abundance of Dubosiella and Akkermansia. In conclusion, CA supplementation could effectively alleviate DSS-induced colitis by improving the defense against oxidative stress and inflammatory response.

Bile acids are critical for lipid absorption, however, their new roles in maintaining or regulating systemic metabolism are irreplaceable. The negative impacts of heat stress (HS) on growth performance, lipid metabolism, and antioxidant status have been reported, but it remains unknown whether the bile acids (BA) composition of broiler chickens can be affected by HS. Therefore, this study aimed to investigate the modulating effects of the environment (HS) and whether dietary BA supplementation can benefit heat-stressed broiler chickens. A total of 216 Arbor Acres broilers were selected with a bodyweight approach average and treated with thermal neutral (TN), HS (32°C), or HS-BA (200 mg/kg BA supplementation) from 21 to 42 days. The results showed that an increase in average daily gain (P < 0.05) while GSH-Px activities (P < 0.05) in both serum and liver were restored to the normal range were observed in the HS-BA group. HS caused a drop in the primary BA (P = 0.084, 38.46%) and Tauro-conjugated BA (33.49%) in the ileum, meanwhile, the secondary BA in the liver and cecum were lower by 36.88 and 39.45% respectively. Notably, results were consistent that SBA levels were significantly increased in the serum (3-fold, P = 0.0003) and the ileum (24.89-fold, P < 0.0001). Among them, TUDCA levels (P < 0.01) were included. Besides, BA supplementation indeed increased significantly TUDCA (P = 0.0154) and THDCA (P = 0.0003) levels in the liver, while ileal TDCA (P = 0.0307), TLCA (P = 0.0453), HDCA (P = 0.0018), and THDCA (P = 0.0002) levels were also increased. Intestinal morphology of ileum was observed by hematoxylin and eosin (H&E) staining, birds fed with BA supplementation reduced (P = 0.0431) crypt depth, and the ratio of villous height to crypt depth trended higher (P = 0.0539) under the heat exposure. Quantitative RT-PCR showed that dietary supplementation with BA resulted in upregulation of FXR (P = 0.0369), ASBT (P = 0.0154), and Keap-1 (P = 0.0104) while downregulation of iNOS (P = 0.0399) expression in ileum. Moreover, 16S rRNA gene sequencing analysis and relevance networks revealed that HS-derived changes in gut microbiota and BA metabolites of broilers may affect their resistance to HS. Thus, BA supplementation can benefit broiler chickens during high ambient temperatures, serving as a new nutritional strategy against heat stress.

Colitis, a chronic inflammatory bowel disease, is characterized by bloody diarrhea and inflammation in the colon. Lonicera hypoglauca (“Shanyinhua” in Chinese) and Scutellaria baicalensis (“Huangqin” in Chinese) are two traditional Chinese medicinal plants rich in polyphenols, such as chlorogenic acid (CGA) and baicalin (BA), with the effects of anti-inflammation and antioxidation. However, it remains unknown whether extracts from L. hypoglauca and S. baicalensis (LSEs) could mitigate colonic inflammation. In the present study, ICR mice (22.23 ± 1.65 g) were allocated to three groups treated with chow diet without (CON) or with dextran sulfate sodium (DSS) (CON+DSS) in water or LSE supplementation in diet with DSS (LSE+DSS), and then inflammatory and oxidative parameters and colonic microbiota were detected. The results showed that LSE (500 mg/kg) treatment mitigated DSS-induced colitis symptoms and restored the shortened colon length, the increased disease activity index (DAI), and the damaged intestinal barrier. In serum, LSE supplementation significantly decreased levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and increased IL-10 level. Meanwhile, superoxide dismutase (SOD) and catalase (CAT) were increased, and malondialdehyde (MDA) and reactive oxygen species (ROS) levels were decreased. In the colon tissue, qPCR results showed that LSE supplementation dramatically downregulated the transcriptional expression of IL-1β, IL-6, TNF-α, and MDA and upregulated the expression of SOD1, CAT, and IL-10. Additionally, the damaged gut barriers occludin and zonula occludens-1 (ZO-1) in the CON+DSS group were enhanced with LSE supplementation. Furthermore, LSE treatment regulated the gut microbial communities with higher relative abundance of Dubosiella and Ruminococcus torques group and lower relative abundance of Bacteroides and Turicibacter. Moreover, the contents of short-chain fatty acids (SCFAs) as products of gut microbiota were also increased. Correlation analysis showed that the mRNA expression of SOD1 was negatively correlated with TNF-α (r = -0.900, P < 0.05); the mRNA expression of IL-6 (r = -0.779, P < 0.05) and TNF-α (r = -0.703, P < 0.05) had a dramatically negative correlation with Dubosiella. In conclusion, LSE supplementation could effectively ameliorate inflammation by modulating oxidative stress and gut microbiota in a colitis mouse model.

The neonatal period is a crucial time during development of the mammalian small intestine. Moreover, neonatal development and maturation of the small intestine are exceptionally important for early growth, successful weaning, and postweaning growth and development, in order to achieve species-specific milestones. Although several publications recently characterized intestinal epithelial cell diversity at the single-cell level, it remains unclear how differentiation and molecular interactions take place between types and subtypes of epithelial cells during the neonatal period. A single-cell RNA sequencing (scRNA-seq) survey of 40,186 ileal epithelial cells and proteomics analysis of ileal samples at 6 time points in the swine neonatal period were performed. The results revealed previously unknown developmental changes: specific increases in undifferentiated cells, unique enterocyte differentiation, and time-dependent reduction in secretory cells. Moreover, we observed specific transcriptional factors, ligand-receptor pairs, G protein-coupled receptors, transforming growth factor β, bone morphogenetic protein signaling pathways, and gut mucosal microbiota playing vital roles in ileal development during the neonatal window. This work offers new comprehensive information regarding ileal development throughout the neonatal period. Reference to this data set may assist in the creation of novel interventions for inflammation-, metabolism-, and proliferation-related gut pathologies. IMPORTANCE We found previously unknown neonatal ileum developmental potentials: specific increases in undifferentiated cells, unique enterocyte differentiation, and time dependent reduction in secretory cells. Specific transcriptional factors (TFs), ligand-receptor pairs, G protein-coupled receptors, transforming growth factor β, bone morphogenetic protein signaling pathways, and the gut mucosal microbiota are involved in this process. Our results may assist in the creation of novel interventions for inflammation-, metabolism-, and proliferation-related gut pathologies.

Intestinal infections in piglets are the main causes of morbidity before and after weaning. Studies have not explored approaches for combining pre-weaning and post-weaning nutritional strategies to sustain optimal gut health. The current study thus sought to explore the effects of early-life nutrition interventions through administration of synthetic milk on growth performance and gut health in piglets from 3 to 30 days of age. Twelve sows were randomly allocated to control group (CON) and early-life nutrition interventions group (ENI). Piglets were fed with the same creep diet from 7 days of age ad libitum. Piglets in the ENI group were provided with additional synthetic milk from Day 3 to Day 30. The results showed that early-life nutrition interventions improved growth performance, liver weight, spleen weight, and reduced diarrhea rate of piglets after weaning (P < 0.05). Early-life nutrition interventions significantly upregulated expression of ZO-1, Occludin, Claudin4, GALNT1, B3GNT6, and MUC2 in colonic mucosa at mRNA level (P < 0.05). Early-life nutrition interventions reduced activity of alkaline phosphatase (AKP) in serum and the content of lipopolysaccharides (LPS) in plasma (P < 0.05). The number of goblet cells and crypt depth of colon of piglets was significantly higher in piglets in the ENI group relative to that of piglets in the CON group (P < 0.05). The relative mRNA expression levels of MCP-1, TNF-α, IL-1β, and IL-8, and the protein expression levels of TNF-α, IL-6, and IL-8 in colonic mucosa of piglets in the ENI group were lower compared with those of piglets in the CON group (P < 0.05). Relative abundance of Lactobacillus in colonic chyme and mucosa of piglets in the ENI group was significantly higher relative to that of piglets in the CON group (P < 0.05). Correlation analysis indicated that abundance of Lactobacillus was positively correlated with the relative mRNA expression levels of ZO-1, Claudin4, and GALNT1, and it was negatively correlated with the level of MCP-1 in colonic chyme and mucosa. In summary, the findings of this study showed that early-life nutrition interventions improved growth performance, colonic barrier, and reduced inflammation in the colon by modulating composition of gut microbiota in piglets. Early-life nutrition intervention through supplemental synthetic milk is a feasible measure to improve the health and reduce the number of deaths of piglets.

Xylo-oligosaccharides (XOS) are considered as functional oligosaccharides and have great prebiotic potential. XOS are the degraded products of xylan prepared via chemical, physical or enzymatic degradation. They are mainly composed of xylose units linked by β-1, 4 bonds. XOS not only exhibit some specific physicochemical properties such as excellent water solubility and high temperature resistance, but also have a variety of functional biological activities including anti-inflammation, antioxidative, antitumor, antimicrobial properties and so on. Numerous studies have revealed in the recent decades that XOS can be applied to many food and feed products and exert their nutritional benefits. XOS have also been demonstrated to reduce the occurrence of human health-related diseases, improve the growth and resistance to diseases of animals. These effects open a new perspective on XOS potential applications for human consumption and animal production. Herein, this review aims to provide a general overview of preparation methods for XOS, and will also discuss the current application of XOS to human and animal health field. ispartof: FRONTIERS IN NUTRITION vol:8 ispartof: location:Switzerland status: published

Intestinal dysfunction of farm animals, such as intestinal inflammation and altered gut microbiota, is the critical problem affecting animal welfare, performance and farm profitability. China has prohibited the use of antibiotics to improve feed efficiency and growth performance for farm animals, including poultry, in 2020. With the advantages of maintaining gut homeostasis, enhancing digestion, and absorption and modulating gut microbiota, organic acids are regarded as promising antibiotic alternatives. Butyric and citric acids as presentative organic acids positively impact growth performance, welfare, and intestinal health of livestock mainly by reducing pathogenic bacteria and maintaining the gastrointestinal tract (GIT) pH. This review summarizes the discovery of butyric acid (BA), citric acid (CA) and their salt forms, molecular structure and properties, metabolism, biological functions and their applications in poultry nutrition. The research findings about BA, CA and their salts on rats, pigs and humans are also briefly reviewed. Therefore, this review will fill the knowledge gaps of the scientific community and may be of great interest for poultry nutritionists, researchers and feed manufacturers about these two weak organic acids and their effects on intestinal health and gut microbiota community, with the hope of providing safe, healthy and nutrient-rich poultry products to consumers.

Xylooligosaccharide (XOS) has tremendous prebiotic potentials for gut health, but the relevant mechanisms are unclear. Herein, we confirmed the positive effects of dietary XOS enhancing gut barrier in a pig model via suppressing the expression of pro-inflammatory cytokines (IL-6 and IL-8). Meanwhile, XOS increased beneficial microbes Lactobacillus and decreased potential pathogenic bacteria. Moreover, XOS augmented microbiota-derived metabolites (mainly butyrate, propionate, and secondary bile acid) to strengthen the gut barrier and regulate gut immunity through activating host G-protein coupled receptors 109a or inhibiting histone deacetylases. Furthermore, XOS attenuated IgA-production and antigen cross-presentation processes. In addition, XOS supplementation led to the alteration of cell proliferation, remodeling of the energy metabolism, activation processes of serial genes or proteins, increased molecular chaperones, and the enhanced ubiquitin-proteasome pathway in cecal cells. Collectively, these results suggest that XOS enhances gut barrier and modulates gut immunity by optimizing gut microbiota and their metabolites, which is associated with alterations of biological processes.

Background: Increasing evidence suggests that antibiotic administration causes gut injury, nutrient digestion, immune regulation, and colonization resistance against pathogens due to the disruption of gut microbiota. However, the time-course effects of therapeutic antibiotics on alterations of gut microbes and short-chain fatty acid in young swine are still unknown. In this study, twenty piglets were assigned into two groups and fed commercial diets with or without lincomycin in the first week for a 28-day trial period. Results: Data showed that one-week lincomycin exposure did reduce the body weight on day 14 (p = 0.0450) and 28 (p = 0.0362). The alpha-diversity notably reduced after one-week lincomycin treatment, then gradually raised and reached the control group level in the second week on cessation of lincomycin exposure, indicated by the variation of Sobs, Chao, Shannon, and ACE index (p < 0.05). Beta-diversity analysis revealed that the distinct microbial cluster existed persistently for the whole trial period between two groups (p < 0.001). The relative abundance of most microbes including fiber-degrading (e.g., Agathobacter, Coprococcus, etc.), beneficial (e.g., Lactobacillus, Mitsuokella, etc.), or pathogenic bacteria (e.g., Terrisporobacter, Lachnoclostridium, etc.) decreased and the concentration of short-chain fatty acids also diminished in the feces of one-week lincomycin-administrated young swine (LDA score > 3). After the lincomycin administration stopped, the state of gut dysbiosis gradually recovered and formed new gut-microbe homeostasis distinct from microbial homeostasis of young pigs unexposed to lincomycin. The increased presence of potential pathogens, such as Terrisporobacter, Negativibacillus, Escherichia-Shigella, etc. and decreased beneficial bacteria such as Lactobacillus, Agathobacter were observed in new homeostasis reshaped by short-lincomycin administration (LDA score > 3 or p < 0.05), adversely affecting gut development and health of young pigs. Conclusion: Collectively, these results suggested that severe disruption of the commensal microbiota occurred after short-term lincomycin exposure or termination of lincomycin exposure in young swine. Our study depicts the change rule of gut microbiota in young animals under the condition of short-term lincomycin treatment, providing basic data for evaluating the harmful impact on gut microbe of young animals.

Aim Weaning stress can cause serious damage to piglet's health. Chlortetracycline (CTC) is widely used to ameliorate weaning stress and prevent infectious diseases in weaned piglets. However, antibiotics as growth promoters have to be limited because of increased antimicrobial resistance. In this study, we evaluated the effects of CTC on growth performance and intestinal functions in order to provide evidence for seeking antibiotic substitutes in weaned piglets. Methods and results A total of 20 weaned piglets were fed a basal diet or a diet supplemented with 75 mg/kg CTC. CTC decreased the crypt depth and increased the ratio of villus height to crypt depth, whilst failing to affect growth performance and serum biochemical parameters and cytokines. 16S rRNA sequencing suggested that CTC supplementation had no effect on the diversity and composition of colonic microbiota. Conclusion We speculated that gut microbiota is no longer sensitive to a low concentration of CTC due to the long-term use and low bioavailability of CTC in weaned piglets.

Feelings of hunger and satiety are the key determinants for maintaining the life of humans and animals. Disturbed appetite control may disrupt the metabolic health of the host and cause various metabolic disorders. A variety of factors have been implicated in appetite control, including gut microbiota, which develop the intricate interactions to manipulate the metabolic requirements and hedonic feelings. Gut microbial metabolites and components act as appetite-related signaling molecules to regulate appetite-related hormone secretion and the immune system, or act directly on hypothalamic neurons. Herein, we summarize the effects of gut microbiota on host appetite and consider the potential molecular mechanisms. Furthermore, we propose that the manipulation of gut microbiota represents a clinical therapeutic potential for lessening the development and consequence of appetite-related disorders. Video abstract video file.(99M, mp4) Supplementary Information The online version contains supplementary material available at 10.1186/s40168-021-01093-y.

Ammonia, an atmospheric pollutant in the air, jeopardizes immune function, and perturbs metabolism, especially lipid metabolism, in human and animals. The roles of intestinal microbiota and its metabolites in maintaining or regulating immune function and metabolism are irreplaceable. Therefore, this study aimed to investigate how aerial ammonia exposure influences hindgut microbiota and its metabolites in a pig model. Twelve growing pigs were treated with or without aerial ammonia (35 mg/m3) for 25 days, and then microbial diversity and microbiota-derived metabolites were measured. The results demonstrated a decreasing trend in leptin (p = 0.0898) and reduced high-density lipoprotein cholesterol (HDL-C, p = 0.0006) in serum after ammonia exposure. Besides, an upward trend in hyocholic acid (HCA), lithocholic acid (LCA), hyodeoxycholic acid (HDCA) (p < 0.1); a downward trend in tauro-deoxycholic acid (TDCA, p < 0.1); and a reduced tauro-HDCA (THDCA, p < 0.05) level were found in the serum bile acid (BA) profiles after ammonia exposure. Ammonia exposure notably raised microbial alpha-diversity with higher Sobs, Shannon, or ACE index in the cecum or colon and the Chao index in the cecum (p < 0.05) and clearly exhibited a distinct microbial cluster in hindgut indicated by principal coordinate analysis (p < 0.01), indicating that ammonia exposure induced alterations of microbial community structure and composition in the hindgut. Further analysis displayed that ammonia exposure increased the number of potentially harmful bacteria, such as Negativibacillus, Alloprevotella, or Lachnospira, and decreased the number of beneficial bacteria, such as Akkermansia or Clostridium_sensu_stricto_1, in the hindgut (FDR < 0.05). Analysis of microbiota-derived metabolites in the hindgut showed that ammonia exposure increased acetate and decreased isobutyrate or isovalerate in the cecum or colon, respectively (p < 0.05). Unlike the alteration of serum BA profiles, cecal BA data showed that high ammonia exposure had a downward trend in cholic acid (CA), HCA, and LCA (p < 0.1); a downward trend in deoxycholic acid (DCA) and HDCA (p < 0.05); and an upward trend in glycol-chenodeoxycholic acid (GCDCA, p < 0.05). Mantel test and correlation analysis revealed associations between microbiota-derived metabolites and ammonia exposure-responsive cecal bacteria. Collectively, the findings illustrated that high ammonia exposure induced the dysbiotic microbiota in the hindgut, thereby affecting the production of microbiota-derived short-chain fatty acids and BAs, which play a pivotal role in the modulation of host systematic metabolism.

The energy values of solvent-extracted canola meal (SECM) and expeller-derived canola meal (EDCM) for broiler chickens and growing pigs were determined in 2 experiments using the regression method. Corn–soybean meal reference diet (RF) and 4 test diets were prepared. The test diets consisted of SECM or EDCM that partly replaced the energy sources in the RF at 100 or 200 g/kg, respectively. The ratios of all energy ingredients were kept similar across all experimental diets. In Exp. 1, a total of 300 birds were fed standard broiler starter diet from days 0 to 19 posthatching. On day 19, 240 birds (776 ± 79.3 g initial BW) were assigned into 5 experimental diets in a randomized complex block design with BW as a blocking factor. Excreta were collected from days 23 to 25 and ileal digesta were collected after birds were euthanized by CO2 asphyxiation on day 26. In Exp. 2, 40 barrows (28.4 ± 1.6 kg initial BW) were allotted to 5 experimental diets according to the randomized complete block design with BW as a blocking factor. After 5-d adaption period, the feces and urine samples were collected for 5 d by total collection method. The ileal digestible energy (IDE), apparent ME (AME), and nitrogen-corrected apparent ME (AMEn) in Exp. 1 and the DE, AME, and AMEn in Exp. 2 for experimental diets and canola meals were determined. In Exp. 1, the inclusion of canola meals to RF linearly decreased the IDE, AME, and AMEn for birds fed SECM diets (P < 0.01) and the AME and AMEn for birds fed EDCM diets (P < 0.01). Furthermore, quadratic effects were also found in the IDE, AME, and AMEn by the inclusion of EDCM to RF (P < 0.05). The IDE were 2,194 and 3,514 kcal/kg DM for SECM and EDCM in broiler chickens, respectively. The respective ME and MEn values were 1,919 and 1,695 kcal/kg DM for SECM and 3,134 and 2,937 kcal/kg DM for EDCM. In Exp. 2, the SECM or EDCM addition to RF linearly decreased the AME and AMEn for pigs (P < 0.01). The DE content was also decreased linearly with the increasing level of SECM (P < 0.01). The DE, ME, and MEn of SECM for pigs were 3,109, 2,891, and 2,655 kcal/kg DM, respectively. The EDCM contained 3,850 kcal of DE, 3,581 kcal of ME, and 3,491 kcal of MEn/kg DM for pigs. In conclusion, the energy values of EDCM are greater than those of SECM for broiler chickens and pigs, and pigs utilize more of the GE in SECM and EDCM than broiler chickens.

Oxidative stress, one of the most common biological dysfunctions, is usually associated with pathological conditions and multiple diseases in humans and animals. Chinese olive fruit (Canarium album L.) extracts (OE) are natural plant extracts rich in polyphenols (such as hydroxytyrosol, HT) and with antioxidant, anti-hyperlipidemia, and anti-inflammatory potentials. This study was conducted to investigate the antioxidant capacity of OE supplementation and its related molecular mechanism in mice. Mice (25.46 ± 1.65 g) were treated with 100 mg/kg body weight (BW) OE or saline solution for 4 weeks, and then the antioxidant and anti-inflammatory capacities of mice were examined. The results showed that OE supplement significantly increased the serum antioxidative enzyme activities of total antioxidant activity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase and decreased the serum malondialdehyde (MDA) level, indicating that OE treatment enhanced the antioxidant capacity in mice. qPCR results showed that the transcriptional expression of antioxidant SOD1, CAT, Gpx1, and Gpx2 were significantly down-regulated in the small intestine (jejunum and ileum) after OE administration. Meanwhile, OE treatment significantly decreased the T-AOC and increased the MDA level in the small intestine. Furthermore, OE administration dramatically reduced the mRNA expression of pro-inflammatory cytokines (TNF-α and IL-1β), which confirmed its antioxidant and anti-inflammatory capacities with OE administration. Using amplicon sequencing technology, 16S rRNA sequencing results showed that OE supplement significantly increased the colonic Firmicutes/Bacteroidetes ratio, which also had a negative correlation with the serum MDA level and positively correlated with serum GSH-Px activity through Pearson correlation analysis. Besides that, Alloprevotella was negatively correlated with serum T-AOC. Colidextribacter was positively correlated with serum MDA and negatively correlated with serum T-AOC, SOD, and GSH-Px levels. In summary, this study showed that treatment with 100 mg/kg BW polyphenol-rich OE could alter colonic microbiota community, which was strongly associated with improved antioxidant capacity in mice.

The objective of this study was to investigate the effects of xylo-oligosaccharides (XOSs) supplementation on growth performance, serum parameters, small intestinal morphology, intestinal mucosal integrity, and immune function in weaned piglets. A total of 240 weaned piglets with an average body weight (BW) of 8.82 ± 0.05 kg (28 d of age) were assigned randomly to four dietary treatments in a 28-d trial, including a control (CON) diet and three diets with XOS supplementation at the concentration of 100 (XOS100), 500 (XOS500), and 1,000 (XOS1000) mg/kg. There were four replicates per treatment with 15 pigs per pen. From day 1 to 14, there were no differences (P > 0.05) in average daily gain (ADG), average daily feed intake, and gain to feed ratio (G:F) during the different treatments. The different doses of XOSs showed a quadratic effect on BW on day 28, ADG, and G:F on day 1 to 28 of piglets (P < 0.05). From day 15 to 28, ADG of pigs fed the XOS500 diet was higher (P < 0.05) than pigs fed the CON diet. During the overall period (day 1 to 28), pigs fed the XOS500 diet had a higher BW, ADG, and G:F than pigs fed the CON diet (P < 0.05). In addition, compared with the CON group, the XOS500 group had significantly higher serum total antioxidant capacity, total superoxide dismutase and catalase levels, and lower malondialdehyde levels on days 14 and 28 (P < 0.05). The serum immunoglobulin G (IgG) concentration in the XOS500 group was also significantly higher compared with the CON group on days 14 and 28 (P < 0.05). However, serum immunoglobulin A and immunoglobulin M were not affected by the dietary treatments. Supplementation of XOS500 to the feed significantly increased the villus height (VH) and VH to crypt depth ratio in the jejunum and ileum in comparison with the CON and XOS1000 groups. Moreover, the XOS500 group significantly elevated the expression levels of occludin and zonula occludens protein-1 in the ileum compared with the CON group. The ileal interleukin (IL)-1β, IL-8, and interferon (IFN)-γ mRNA expression levels in the XOS100 and XOS500 groups were markedly lower than in the CON group. In contrast, the ileal IL-10 mRNA expression levels were remarkably higher in the XOS500 than in the CON group. In conclusion, XOSs have a beneficial effect on growth performance by improving serum antioxidant defense system, serum IgG, small intestinal structure, and intestinal barrier function in weaned piglets.