ABSTRACT. The ratio of Bacteroidetes and Firmicutes bacterial groups in the gut can affect the ability to absorb nutrients. We investigated the effect of probiotic Bacillus subtilis supplementation of diets on growth performance, fat deposition, blood lipids, copy numbers, and percentage of Bacteroidetes and Firmicutes in cecal contents, as well as mRNA expression of key lipid metabolism enzymes in the liver and adipose tissue of finishing pigs. Twenty-four Duroc x Meishan crossbreed 8-week-old pigs (10.28 ± 0.59 kg) were randomly allocated to two dietary treatments: maize-soybean mealbased diets with B. subtilis (probiotic group) and without B. subtilis (control group). The probiotic diet led to a significant increase in the average daily gain and feed conversion ratio of pigs weighing 10 to 110 kg. The mean backfat depth was increased while leaf lard weights were decreased by probiotic supplementation. Ingestion of probiotics decreased the serum triglyceride and glucose concentrations, but did not change the levels of total cholesterol and free fatty acids in the serum. The mRNA expressions of fatty acid synthase (FAS) and acetylCoA carboxylase α (ACCα) in the liver were down-regulated by the dietary probiotic supplement. Conversely, the gene expressions of FAS and ACCα in the adipose tissue increased. The probiotic diet decreased the copy numbers and percentage of Bacteroidetes, while it increased the percentage of Firmicutes in the cecal contents. We conclude that the addition of B. subtilis improves growth performance and up-regulates lipid metabolism in subcutaneous fat of finishing pigs. We conclude that B. subtilis affects lipid metabolism through regulation of the proportion of Bacteroidetes and Firmicutes in the gut.

Previous studies have suggested that immune system development and weaning stress are closely related to the maturation of gut microbiota. The early-life period is a "window of opportunity" for microbial colonization, which potentially has a critical impact on the development of the immune system. Fecal microbiota transplantation (FMT) and probiotics are often used to regulate gut microbial colonization. This study aims to test whether early intervention with FMT using fecal microbiota from gestation sows combined with Clostridium butyricum and Saccharomyces boulardii (FMT-CS) administration could promote the maturation of gut microbiota and development of immune system in piglets. Piglets were assigned to control (n = 84) and FMT-CS treatment (n = 106), which were treated with placebo and bacterial suspension during the first three days after birth, respectively. By 16S rRNA gene sequencing, we found that FMT-CS increased the α-diversity and reduced the unweighted UniFrac distances of the OTU community. Besides, FMT-CS increased the relative abundance of beneficial bacteria, while decreasing that of opportunistic pathogens. FMT-CS also enhanced the relative abundance of genes related to cofactors and vitamin, energy, and amino acid metabolisms during the early-life period. ELISA analysis revealed that FMT-CS gave rise to the plasma concentrations of IL-23, IL-17, and IL-22, as well as the plasma levels of anti-M.hyo and anti-PCV2 antibodies. Furthermore, the FMT-CS-treated piglets showed decreases in inflammation levels and oxidative stress injury, and improvement of intestinal barrier function after weaning as well. Taken together, our results suggest that early-life intervention with FMT-CS could promote the development of innate and adaptive immune system and vaccine efficacy, and subsequently alleviate weaning stress through promoting the maturation of gut microbiota in piglets.

Bacterial vaginosis (BV) is the most common vaginal infection found inwomen in the world. Due to increasing drug-resistance of virulent pathogen such as Gardnerella vaginalis (G. vaginalis), more than half of BV patients suffer recurrence after antibotics treatment. Here, metastable iron sulfides (mFeS) act in a Gram-dependent manner to kill bacteria, with the ability to counteract resistant G. vaginalis for BV treatment. With screening of iron sulfide minerals, metastable Fe 3 S 4 shows suppressive effect on bacterial growth with an order: Gram-variable G. vaginalis >Gram-negative bacteria>> Gram-positive bacteria. Further studies on mechanism of action (MoA) discover that the polysulfide species released from Fe 3 S 4 selectively permeate bacteria with thin wall and subsequently interrupt energy metabolism by inhibiting glucokinase in glycolysis, and is further synergized by simultaneously released ferrous iron that induces bactericidal damage. Such multiple MoAs enable Fe 3 S 4 to counteract G. vaginalis strains with metronidazole-resistance and persisters in biofilm or intracellular vacuole, without developing new drug resistance and killing probiotic bacteria. The Fe 3 S 4 regimens successfully ameliorate BV with resistant G. vaginalis in mouse models and eliminate pathogens from patients suffering BV. Collectively, mFeS represent an antibacterial alternative with distinct MoA able to treat challenged BV and improve women health.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide.

Dietary fiber, an important regulator of intestinal microbiota, is a promising tool for preventing obesity and related metabolic disorders. However, the functional links between dietary fiber, intestinal microbiota, and obesity phenotype are still not fully understood. Combined soluble fiber (CSF) is a synthetic mixture of polysaccharides and displays high viscosity, water-binding capacity, swelling capacity, and fermentability. We found that supplementing high-fat diet (HFD) with 6% CSF significantly improved the insulin sensitivity of obese mice without affecting their body weight. Replacing the HFD with normal chow basal diet (NCD), the presence of CSF in the feed significantly enhanced satiety, decreased energy intake, promoted weight and fat loss, and augmented insulin sensitivity. CSF also improved the intestinal morphological integrity, attenuated systemic inflammation, promoted intestinal microbiota homeostasis, and stabilized the production of short-chain fatty acids (SCFAs) that was perturbed during HFD-induced obesity, and these stabilizing effects were more prominent when the basal diet was switched to NCD. The enrichment of bacteria of the S24-7 family and Allobaculum genus increased markedly in the intestine following 6% CSF supplementation- and correlated with decreased adiposity and insulin resistance. Five bacterial genera that were decreased by CSF, including Oscillospira, unclassified Lachonospitaceae, unclassified Clostridiales, unclassified Desulfovibrionaceae, and unclassified Ruminococcae, were subjected to co-occurrence network analysis and were positively correlated to adiposity and insulin resistance, indicating a key role in the microbial response to CSF. Thus, CSF has a potential to promote insulin sensitivity and even reduce obesity via beneficial regulation of the gut microecosystem.

Paneth cells are a group of unique intestinal epithelial cells, and they play an important role in host-microbiota interactions. At the origin of Paneth cell life, several pathways such as Wnt, Notch, and BMP signaling, affect the differentiation of Paneth cells. After lineage commitment, Paneth cells migrate downward and reside in the base of crypts, and they possess abundant granules in their apical cytoplasm. These granules contain some important substances such as antimicrobial peptides and growth factors. Antimicrobial peptides can regulate the composition of microbiota and defend against mucosal penetration by commensal and pathogenic bacteria to protect the intestinal epithelia. The growth factors derived from Paneth cells contribute to the maintenance of the normal functions of intestinal stem cells. The presence of Paneth cells ensures the sterile environment and clearance of apoptotic cells from crypts to maintain the intestinal homeostasis. At the end of their lives, Paneth cells experience different types of programmed cell death such as apoptosis and necroptosis. During intestinal injury, Paneth cells can acquire stem cell features to restore the intestinal epithelial integrity. In view of the crucial roles of Paneth cells in the intestinal homeostasis, research on Paneth cells has rapidly developed in recent years, and the existing reviews on Paneth cells have mainly focused on their functions of antimicrobial peptide secretion and intestinal stem cell support. This review aims to summarize the approaches to studying Paneth cells and introduce the whole life experience of Paneth cells from birth to death.

Maternal obesity disrupts both placental angiogenesis and fetus development. However, the links between adipocytes and endothelial cells in maternal obesity are not fully understood. The aim of this study was to characterize exosome-enriched miRNA from obese sow’s adipose tissue and evaluate the effect on angiogenesis of endothelial cells. Plasma exosomes were isolated and analyzed by nanoparticle tracking analysis (NTA), electron morphological analysis, and protein marker expression. The number of exosomes was increased as the gestation of the sows progressed. In addition, we found that exosomes derived from obese sows inhibited endothelial cell migration and angiogenesis. miRNA detection showed that miR-221, one of the miRNAs, was significantly enriched in exosomes from obese sows. Further study demonstrated that exosomal miR-221 inhibited the proliferation and angiogenesis of endothelial cells through repressing the expression of Angptl2 by targeting its 3′ untranslated region. In summary, miR-221 was a key component of the adipocyte-secreted exosomal vesicles that mediate angiogenesis. Our study may be a novel mechanism showing the secretion of “harmful” exosomes from obesity adipose tissues causes placental dysplasia during gestation.

Early intervention with fecal microbiota transplantation (FMT) improves the growth performance and intestinal barrier function of piglets. Accelerating intestinal oxygen concentration is beneficial for symbiotic bacterial colonization. Saccharomyces boulardii (SB) is an aerobic fungus, which may contribute to the colonization of anaerobic symbiotic bacteria by competing for oxygen. Clostridium butyricum (CB) improves intestinal barrier function and performance, via regulating the gut microbiota composition of piglets. The objective of this study was to investigate the effect of early intervention with FMT combining CB and SB on growth performance, diarrhea, and intestinal barrier function in piglets. A total of 77 litters of neonatal piglets assigned to one of six treatments, which treated with antibiotics (AB), placebo (CON), and FMT (FMT), FMT-added CB (FMT+C), FMT-added SB (FMT+S), and FMT-added CB and SB (FMT+C+S), respectively. FMT+C+S treated piglets had higher body weight (BW) and average daily gain (ADG) both in weaning and finial period, and it significantly increased the levels of fecal mucin-2 (MUC2), fecal short-chain fatty acids (SCFAs), and relative abundance of fecal Lactobacillus spp., and Bifidobacterium genus. Moreover, early intervention with FMT+C+S reduced the diarrhea rate during the experiment. FMT+C+S also decreased the level of plasma diamine oxidase (DAO) and D-lactate (D-LA), and relative abundance of fecal E. coli during the suckling period. In summary, early intervention with FMT combining CB and SB improved the growth performance, intestinal barrier function, fecal SCFAs concentration, and fecal Lactobacillus and Bifidobacterium of piglets.