Small Intestinal Bacterial Overgrowth (SIBO) and Twelve Groups of Related Diseases-Current State of Knowledge.

The human gut microbiota creates a complex microbial ecosystem, characterized by its high population density, wide diversity, and complex interactions. Any imbalance of the intestinal microbiome, whether qualitative or quantitative, may have serious consequences for human health, including small intestinal bacterial overgrowth (SIBO). SIBO is defined as an increase in the number of bacteria (103-105 CFU/mL), an alteration in the bacterial composition, or both in the small intestine. The PubMed, Science Direct, Web of Science, EMBASE, and Medline databases were searched for studies on SIBO and related diseases. These diseases were divided into 12 groups: (1) gastrointestinal disorders; (2) autoimmune disease; (3) cardiovascular system disease; (4) metabolic disease; (5) endocrine disorders; (6) nephrological disorders; (7) dermatological diseases; (8) neurological diseases (9); developmental disorders; (10) mental disorders; (11) genetic diseases; and (12) gastrointestinal cancer. The purpose of this comprehensive review is to present the current state of knowledge on the relationships between SIBO and these 12 disease groups, taking into account risk factors and the causal context. This review fills the evidence gap on SIBO and presents a biological-medical approach to the problem, clearly showing the groups and diseases having a proven relationship with SIBO, as well as indicating groups within which research should continue to be expanded.

Differential effects of Bacillus subtilis- and Bacillus licheniformis-fermented products on growth performance, intestinal morphology, intestinal antioxidant and barrier function gene expression, cecal microbiota community, and microbial carbohydrate-active enzyme composition in broilers.

This study investigated the differential effects of Bacillus subtilis-fermented products (SFPs) and Bacillus licheniformis-fermented products (LFPs) on the growth performance, intestinal morphology, intestinal gene expression, cecal microbiota community, and microbial carbohydrate-active enzyme composition of broilers. In total, 160 one-day-old unsexed Arbor Acres broiler chicks were randomly allocated to 4 treatment groups (with 8 replicates per group and 5 chicks per replicate): control (CON), enramycin (ENM), SFP, and LFP groups, which were fed a basal diet, basal diet supplemented with 10 mg/kg ENM, basal diet supplemented with 108 colony-forming units (CFU) of B. subtilis spores per gram of feed, and basal diet supplemented with 108 CFU of B. licheniformis spores per gram of feed, respectively. LFP treatment resulted in a higher (P < 0.01) body weight at the age of 35 d and higher average daily gain over 15 to 35 (P < 0.05) and 1 to 35 (P < 0.05) d of age than did the CON and SFP treatments. The average villus heights in the jejunum were longer (P < 0.05) in the LFP group than those in the SFP group. Moreover, the LFP group exhibited a higher jejunal barrier function gene expression (mucin 2, zonula occludens-1, and occludin) and cecal antioxidant gene expression (superoxide dismutase) than did the CON group (P < 0.05). A principal coordinate analysis of cecal microbiota and carbohydrate-active enzyme composition demonstrated distinct clustering among the groups. Lactobacillus crispatus abundance in the cecal digesta was higher (P < 0.01) in the SFP group than in the CON and LFP groups. Finally, microbial glycosyltransferase 2 gene expression in the cecal digesta was higher in the LFP group than in the CON and ENM groups. In conclusion, LFPs can improve the growth performance, increase intestinal barrier function and antioxidant gene expression, and modulate cecal microflora composition and carbohydrate-active enzyme composition of broilers. The overall effect of LFPs on growth promotion in broilers was superior to that of SFPs.

Nano Modification of Antrodia Cinnamomea Exhibits Anti-Inflammatory Action and Improves the Migratory Potential of Myogenic Progenitors.

The skeletal muscle progenitors' proliferation and migration are crucial stages of myogenesis. Identifying drug candidates that contribute to myogenesis can have a positive impact on atrophying muscle. The purpose of the study is to synthesize the Antrodia cinnamomea (AC)-ß-cyclodextrin (BCD) inclusion complex (IC) and understand its in vitro pro-regenerative influence in murine skeletal C2C12 myoblasts. The IC was subjected to various nano-characterization studies. Fluorescent IC was synthesized to understand the cellular uptake of IC. Furthermore, 25 µg/mL, 12.5 µg/mL, and 6.25 µg/mL of IC were tested on murine C2C12 skeletal muscle cells for their anti-inflammatory, pro-migratory, and pro-proliferative action. The cellular internalization of IC occurred rapidly via pinocytosis. IC (252.6 ± 3.2 nm size and -37.24 ± 1.55 surface charge) exhibited anti-inflammatory action by suppressing the secretion of interleukin-6 and enhanced cell proliferation with promising cytocompatibility. A 12.5 µg/mL dose of IC promoted cell migration in 24 h, but the same dose of AC significantly reduced cell migration, suggesting modification by BCD. Molecular studies revealed that IC promoted C2C12 myoblasts migration by upregulating long non-coding RNA (lncRNA) NEAT-1, SYISL, and activating the pPKC/ß-catenin pathway. Our study is the first report on the pro-proliferative and pro-migratory effects of BCD-modified extracts of AC.

Bacillus licheniformis-fermented products and enramycin differentially modulate microbiota and antibiotic resistome in the cecal digesta of broilers.

Since antibiotic resistance is a global health issues, the use of antibiotics in animal feed for growth promotion has been restricted in many countries. Bacillus licheniformis probiotic is a potential alternative to antibiotics for increasing poultry performance. Through metagenomic sequencing, this study investigated the effects of B. licheniformis-fermented products (BLFPs) and enramycin on the microbial community composition and antibiotic resistance gene (ARG) distribution in the cecal digesta of broilers at the age of 35 d. In total, 144 one-day-old male broiler chicks (Ross 308) were randomly assigned to 4 dietary treatments as follows: basal diet (control [C] group), basal diet plus 10 mg/kg enramycin (E group), basal diet plus 1 g/kg BLFPs (L group), and basal diet plus 3 g/kg BLFPs (H group), with 6 replicate cages per treatment group and 6 birds per cage. The results indicated that the cecal alpha diversity (richness and evenness) of bacterial species was higher in the H group than in the C group. Principal coordinate analysis of microbiota and the ARG composition indicated clear differences among the cecal samples of the groups. In the cecal digesta, the abundance of active bacteria associated with probiotic properties, such as Lactobacillus crispatus and Akkermansia muciniphila, was higher in the H group than in the other groups. Enramycin treatment promoted the expression of peptide (bcrA), glycopeptide (vanRI), and lincosamide (lsaE) resistance genes but inhibited the expression of aminocoumarin (parY) and pleuromutilin (TaeA) resistance genes. BLFP (1 and 3 g/kg) treatment suppressed the expression of aminoglycoside (ANT(6)-Ib), streptogramin (vatB), and peptide (ugd) resistance genes but enhanced the expression of macrolide (efrA) and aminocoumarin (novA) resistance genes. The abundance of peptide resistance genes in Bacteroides spp. was lower in the H group than in the C group. The abundance of lincosamide resistance genes in Lactobacillus spp. was higher in the E group than in the other groups. These results demonstrated that differential changes in the structure of 3 g/kg BLFPs and enramycin-induced cecal microbial communities accompany changes in the abundance of bacterial hosts carrying specific ARGs in the cecal microbiota of broilers.

Antibacterial and Antioxidant Activity of the Fruit of Macaranga tanarius, the Plant Origin of Taiwanese Green Propolis.

Taiwanese green propolis (TGP) is widely used in traditional medicine and exerts a broad spectrum of biological activities, including those anti-inflammatory and anti-cancer in nature, resulting from an abundant level of functional propolins (prenylated flavanone) in the TGP. However, the plant origin of TGP has not been clarified. In this study, we collected the surface material of Macaranga tanarius fruit and comparatively analyzed the chemical composition, antibacterial activity, and antioxidant activity with TGP. The results revealed that there was no difference between the chemical composition of the glandular trichome extract of M. tanarius and those in propolis. Moreover, M. tanarius fruit extract was enriched in propolins (C, D, F, and G) and effectively inhibited the growth of Gram-positive strains. Propolins, TGP, and M. tanarius fruit extract showed powerful free radical-scavenging and ferrous-reducing activity. Collectively, we have confirmed the plant source of TGP is M. tanarius, and this plant has the enormous potential to be developed as a pharmaceutical plant due to the potent biological activities and the high amount of functional propolins.

Extraction and Analysis of Taiwanese Green Propolis.

Taiwanese green propolis is rich in prenylated flavonoids and exhibits a broad range of biological activities, such as antioxidant, antibacterial, and anticancer ones. The bioactive compounds of Taiwanese green propolis are propolins, namely C, D, F, and G. The concentration of propolins in Taiwanese green propolis varies depending on the season and geographic location. Thus, it is critical to establish a standard and repeatable procedure for determining the quality of Taiwanese green propolis. Here, we present a protocol that uses ethanol-based extraction, high-performance liquid chromatography, and an antibacterial activity analysis to characterize Taiwanese green propolis quality. This method indicates that 95% and 99.5% ethanol extractions achieve the maximum dry matter yields from Taiwanese green propolis, thereby yielding the highest concentrations of propolins that have antibacterial properties. According to these findings, the present protocol is deemed reliable and repeatable for determining the quality of Taiwanese green propolis.

Effect of Cordyceps militaris Hot Water Extract on Immunomodulation-associated Gene Expression in Broilers, Gallus gallus.

Cordyceps militaris is a well-known Chinese medicinal fungus that has been used as a nutraceutical food in several Asian countries. Cordycepin (3'-deoxyadenosine), a secondary metabolite produced from Cordyceps militaris, has been demonstrated to exert a wide spectrum of pharmacological activities, such as anti-microbial and antitumor activities. However, the effect of cordycepin on immunomodulation in broilers is poorly investigated. In the current study, we investigated the effect of cordycepin (9.69, 19.38, and 38.76 mg) from Cordyceps militaris hot water extract (CMHW) on growth performance and immunocompetence in broilers. Results showed that CMHW significantly decreased inducible nitric oxide synthase (iNOS) mRNA levels in the bursa of Fabricius after 4 weeks of feeding (P<0.05). CMHW treatment reduced cyclooxygenase-2 (COX-2) mRNA levels in the spleen and bursa of Fabricius after 4 weeks of feeding (P<0.05). Supplementation of CMHW for 3 days after vaccination reduced iNOS mRNA level in the spleen of 14 and 28 day-old broilers (P<0.05). Prior to vaccination, CMHW pretreatment significantly down-regulated COX-2 mRNA levels in the spleen and bursa of Fabricius of 14-day-old broilers (P<0.05). Furthermore, CMHW significantly reduced lipopolysaccharide (LPS)-induced iNOS and COX-2 mRNA levels in the spleen and bursa of Fabricius (P<0.05). CMHW treatment attenuated LPS-induced IFN-γ expression in the spleen and bursa of Fabricius, whereas CMHW induced IL-4 expression in these organs in response to LPS challenge (P<0.05). Taken together, these observations demonstrate that CMHW exerts an immunomodulatory role in broilers. CMHW is a potential novel feed additive with applications in inflammation-related diseases and bacterial infection in broilers.

The potential of brown adipogenesis and browning in porcine bone marrow-derived mesenchymal stem cells1.

Brown adipocyte lineage commitment and differentiation are under complex regulation. Brown adipocytes are derived from mesenchymal stem cells (MSC). Whether porcine bone marrow-derived MSC (BM-MSC) possess the potential to differentiate into brown adipocytes remains unclear. In the current study, we evaluated the ability of porcine BM-MSC to differentiate into brown adipocytes and browning of differentiated adipocytes. We found that similar to rodent models, bone morphogenetic protein 7 (BMP7) was able to trigger the commitment of BM-MSC to the brown adipocyte lineage by elevating expression of marker genes, nrf-1, tfam, zic1, and pgc-1α (P < 0.05). The expression of brown adipocyte-specific genes, prdm16, dio2, and cidea, was significantly induced (P < 0.05) in BMP7-treated porcine BM-MSC after hormonal induction of adipogenesis. The UCP2 and UCP3 protein levels in BMP7-treated porcine BM-MSC were higher than the control group after hormonal induction of adipogenesis, accompanied by increased mitochondrial DNA copy number and mitochondria-specific gene expression (P < 0.05). Furthermore, acute norepinephrine stimulation potentiated brown adipocyte-specific mRNA expression (P < 0.05) in differentiated adipocytes. Similarly, UCP2 and UCP3 protein levels were increased in differentiated adipocytes upon acute norepinephrine stimulation. In addition, mitochondrial DNA copy number and mitochondria-specific gene expression were also significantly increased (P < 0.05) in differentiated adipocytes after acute norepinephrine exposure. Taken together, these results demonstrate for the first time that porcine BM-MSC are able to commit to the brown adipocyte lineage and differentiate into brown adipocytes. Differentiated adipocytes derived from porcine BM-MSC have the developmental potential to transdifferentiate into brown-like adipocytes upon norepinephrine stimulation.

Antibacterial activity of propolins from Taiwanese green propolis.

Taiwanese green propolis is a prenylated flavonoid rich honeybee product and propolins isolated from Taiwanese green propolis exert a broad spectrum of biological activities, such as anti-cancer and anti-oxidant. However, the anti-bacterial effects of Taiwanese green propolis or propolins are still poorly understood. In the current study, the antibacterial effects of Taiwanese green propolis and propolins were evaluated. Results show that the maximum dry matter yields of Taiwanese green propolis were observed in the 95% and 99.5% ethanol extracts compared to other extraction methods. Consistently, the highest concentration of propolins C, D, F and G from Taiwanese green propolis was obtained in 95% and 99.5% ethanol extracts. Propolins inhibited the growth of gram-positive bacterial strains (Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes and Paenibacillus larvae). The average minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of propolins from ethanol extracts were 20 µg/ml. Among the propolins, propolin C had the highest antibacterial activity. Furthermore, Taiwanese green propolis also showed antibacterial activity against methicillin-resistant S. aureus (MRSA). In conclusion, these results demonstrate that Taiwanese green propolis and propolins have significant antibacterial activity, particularly against gram-positive bacterial strains.

Deficiency of NPGPx, an oxidative stress sensor, leads to obesity in mice and human.

Elevated oxidative stress is closely associated with obesity. Emerging evidence shows that instead of being a consequence of obesity, oxidative stress may also contribute to fat formation. Nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) is a conserved oxidative stress sensor/transducer and deficiency of NPGPx causes accumulation of reactive oxygen species (ROS). In this communication, we show that NPGPx was highly expressed in preadipocytes of adipose tissue. Deficiency of NPGPx promoted preadipocytes to differentiate to adipocytes via ROS-dependent dimerization of protein kinase A regulatory subunits and activation of CCAAT/enhancer-binding protein beta (C/EBPß). This enhanced adipogenesis was alleviated by antioxidant N-acetylcysteine (NAC). Consistently, NPGPx-deficient mice exhibited markedly increased fat mass and adipocyte hypertrophy, while treatment with NAC ablated these phenotypes. Furthermore, single nucleotide polymorphisms (SNPs) in human NPGPx gene, which correlated with lower NPGPx expression level in adipose tissue, were associated with higher body mass index (BMI) in several independent human populations. These results indicate that NPGPx protects against fat accumulation in mice and human via modulating ROS, and highlight the importance of targeting redox homeostasis in obesity management.

Docosahexaenoic acid suppresses the expression of FoxO and its target genes.

Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, has previously been shown to ameliorate obesity-associated metabolic syndrome. To decipher the mechanism responsible for the beneficial effects of DHA on energy/glucose homeostasis and the metabolic syndrome, 30 weaned cross-bred pigs were randomly assigned to three groups and fed ad libitum with a standard diet supplemented with 2% of beef tallow, soybean oil or DHA oil for 30 days, and the gene expression profile of various tissues was evaluated by quantitative real-time polymerase chain reaction. The DHA-supplemented diets reduced the expression of forkhead box O transcription factor (FoxO) 1 and FoxO3 in the liver and adipose tissue. DHA treatments also decreased the expression of FoxO1 and FoxO3 in human hepatoma cells, SK-HEP-1 and human and porcine primary adipocytes. In addition, DHA also down-regulated FoxO target genes, such as microsomal triacylglycerol transfer protein (MTP), glucose-6-phosphatase, apolipoprotein C-III (apoC-III) and insulin-like growth factor binding-protein 1 in the liver, as well as reduced total plasma levels of cholesterol and triacylglycerol in the pig. Transcriptional suppression of FoxO1, FoxO3, apoC-III and MTP by DHA was further confirmed by reporter assays with each promoter construct. Taken together, our study indicates that DHA modulates lipid and glucose homeostasis in part by down-regulating FoxO function. The down-regulation of genes associated with triacylglycerol metabolism and very low density lipoprotein assembly is likely to contribute to the beneficial effects of DHA on the metabolic syndrome.

The function of porcine PPARγ and dietary fish oil effect on the expression of lipid and glucose metabolism related genes.

Peroxisome-proliferator-activated receptor γ (PPARγ) plays a critical role in regulation of adipocyte differentiation and insulin sensitivity. To become functional, PPARγ must be activated by binding an appropriate ligand. Polyunsaturated fatty acids (PUFA) are potential ligands for PPARγ. The current experiment was designed to determine the potential for PUFA, particularly eicosapentaenoic acid and docosahexaenoic acid, to activate the function of porcine PPARγ in vivo. Transgenic mice, expressing porcine PPARγ in skeletal muscle were generated and fed with a high-saturated fat (beef tallow) or high-unsaturated fat (fish oil) diet for 4 months. When transgenic mice were fed a fish oil supplemented diet, the expression of adipogenic and glucose uptake genes was increased, leading to reduced plasma glucose concentration. The PPARγ transgene increased the expression of Glut4 in the muscle. This result suggests that there was increased glucose utilization and, therefore, a reduced blood glucose concentration in the transgenic mice. Also, the plasma adiponectin was elevated by fish oil treatment, suggesting a role of adiponectin in mediating the PUFA effect. These results suggest that PUFA may serve as a natural regulator of glucose uptake in vivo and these effects are mainly through PPARγ function.