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Methotrexate (MTX) is a widely used therapeutic agent for the treatment of cancer and autoimmune diseases. However, its efficacy is often limited by adverse effects, such as intestinal toxicity. Although treatment with leucovorin (LV) is the most common method to reduce the toxic effects of MTX, it may also compromise the therapeutic effects of MTX. The gut microbiome has been reported to be associated with the intestinal toxicity of MTX. In this study, the intestinal damage of MTX was ameliorated by treatment with LV. Moreover, the population, diversity, and principal components of the gut microbiota in MTX-treated mice were restored by treatment with LV. The only element of the gut microbiota that was significantly changed after treatment with LV was Bifidobacterium, and supplementation with Bifidobacterium longum ameliorated MTX-induced intestinal damage. In conclusion, our results suggest that the balance and the composition of gut microbiota have an important role in the LV-mediated protection against MTX-induced intestinal toxicity. This work provides foundation of data in support of a new potential mechanism for the prevention of MTX-induced intestinal toxicity., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Lactic acid bacteria and bifidobacteria deliberately introduced into the food chain may act as a reservoir of antimicrobial resistance genes (ARGs), which is considered a safety concern. In the present study, resistance to antimicrobials of commercial probiotic strains, probiotic candidate strains, and starter cultures (n = 20) was characterised based on integration of phenotypic and in silico data. Minimum inhibitory concentrations (MICs) of 16 antimicrobials were determined for lactobacilli and bifidobacteria that were isolated from pharmaceutical products or obtained from the manufacturers or culture collections. Using different databases and bioinformatic tools, we predicted ARGs, mutations, genomic islands, and mobile genetic elements (MGEs) in their whole genome sequences. In addition, a comprehensive in silico analysis of the prevalence of the tetW gene and its genetic environment across lactobacilli and bifidobacteria (n = 1423) was conducted. Several strains exhibited phenotypic resistance to kanamycin, tetracycline, chloramphenicol, quinupristin-dalfopristin, ciprofloxacin, or neomycin. These resistances, however, did not always correspond to the presence of ARGs and vice versa. We detected an acquired tetW gene in four commercial strains of Bifidobacterium animalis subsp. lactis, whereas homologs of antimicrobial resistance (AR) proteins were predicted in all 20 proteomes. The prevalence of the tetW gene, which was often flanked by MGEs, was higher in analysed bifidobacteria (31.9%) than lactobacilli (6.3%). In addition, sequences flanking tetW were associated with putative genomic islands and were conserved in several strains, including potential pathogens. Our findings provide an insight into AR of probiotics, probiotic candidates, and starter cultures with an emphasis on tetracycline and into the safety of these strains in the context of AR., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Societal lifestyle changes, especially increased consumption of a high-fat diet lacking dietary fibers, lead to gut microbiota dysbiosis and enhance the incidence of adiposity and chronic inflammatory disease. We aimed to investigate the metabolic effects of inulin with different degrees of polymerization on high-fat diet-fed C57BL/6 J mice and to evaluate whether different health outcomes are related to regulation of the gut microbiota. Short-chain and long-chain inulins exert beneficial effects through alleviating endotoxemia and inflammation. Antiinflammation was associated with a proportional increase in short-chain fatty acid-producing bacteria and an increase in the concentration of short-chain fatty acids. Inulin might decrease endotoxemia by increasing the proportion of Bifidobacterium and Lactobacillus, and their inhibition of endotoxin secretion may also contribute to antiinflammation. Interestingly, the beneficial health effects of long-chain inulin were more pronounced than those of short-chain inulin. Long-chain inulin was more dependent than short-chain inulin on species capable of processing complex polysaccharides, such as Bacteroides. A good understanding of inulin-gut microbiota-host interactions helps to provide a dietary strategy that could target and prevent high-fat diet-induced endotoxemia and inflammation through a prebiotic effect.

We studied the effect of combined antimicrobial therapy with amoxicillin, metronidazole, and clarithromycin on the severity of ischemia/reperfusion myocardial injury in Wistar rats with alimentary obesity and acute inflammation of the large intestine. General ischemia/reperfusion was reproduced on Langendorff-perfused isolated hearts and infarct size was estimated. Acute inflammation of the large intestine was accompanied by an increase in the blood levels of proinflammatory cytokines. The presence of obesity and acute inflammation of the large intestine did not significantly affect the infarct size in comparison with the control. Administration of antimicrobial drugs to animals with obesity and acute inflammation of the large intestine led to a significant increase in the infarct size, which should be considered when prescribing antimicrobial therapy to patients with comorbidity.

Background: Recently, exploring novel dietary nondigestible carbohydrates, which are able to influence the gut flora, has drawn much attention. The objective of this study was to find out the effective dose of levan, as a prebiotic, in rats in order to further apply in food industry., Methods: Levan at various doses (2-10%) was orally administered to male Wistar Albino rats once a day for 90 days. At the end of experiment, fecal and blood samples were collected to measure gut bacteria population and to carry out serum biochemical assay. The rats were sacrificed, and the colon tissues were stained with hematoxylin and eosin and analyzed by histopathology., Results: Of note, levan effectively controlled body weight gain in the rats. Serum biochemical analysis revealed that 5% levan significantly diminished the serum level of total cholesterol, LDL, and glucose as well. More notably, 5% levan intake significantly increased the abundance of bifidobacteria population, highlighting its bifidogenic effect. Furthermore, our histopathological result revealed that daily intake of levan was associated with a higher degree of thickness of the mucosa layer compared to the rats in control group. Moreover, these findings manifested no colon inflammation in the rats fed with levan., Conclusion: The findings of this study provide the fundamental data to use levan at a definite dose for further development in functional foods.

Rhamnogalacturonan-I (RG-I)-enriched pectin (WRP) was recovered from citrus processing water by sequential acid and alkaline treatments in a previous study. RG-I-enriched pectin was proposed as a potential supplement for functional food and pharmaceutical development. However, previous studies illustrated that favorable modulations of gut microbiota by RG-I-enriched pectin were based on in vitro changes in the overall microbial structure and the question of whether there is a structure-dependent modulation of gut microbiota remains largely enigmatic. In the present study, modulations of gut microbiota by commercial pectin (CP), WRP and its depolymerized fraction (DWRP) with different RG-I contents and Mw were compared in vivo. It was revealed by 16s rRNA high-throughput sequencing that WRP and DWRP mainly composed of RG-I modulated the gut microbiota in a positive way. DWRP significantly increased the abundance of prebiotic such as Bifidobacterium spp., Lactobacillus spp., while WRP increased SCFAs producers including species in Ruminococcaceae family. By maintaining a more balanced gut microbiota composition and enriching some SCFA producers, dietary WRP and DWRP also elevated the SCFA content in the colon. Collectively, our findings offer new insights into the structure-activity correlation of citrus pectin and provide impetus towards the development of RG-I-enriched pectin with small molecular weight for specific use in health-promoting prebiotic ingredients and therapeutic products.

Green tea supplementation has beneficial health effects. However, its underlying mechanisms, such as effects on modulating the intestinal microbiome and endogenous metabolome, particularly following short-term supplementation, are largely unclear. We conducted an integrative metabolomics study to evaluate the effects of short-term (7-day) supplementation of green tea extract (GTE) or its components, epigallocatechin gallate, caffeine, and theanine, on the caecum microbiota and caecum/skin metabolome in mice. Further, we established an integrative metabolome-microbiome model for correlating gut and skin findings. The effects of short-term supplementation with dietary compounds were evaluated with respect to UV stress response, with GTE showing the most remarkable effects. Biplot analysis revealed that Bifidobacteria and Lactobacillus spp. were considerably influenced by short-term GTE supplementation, while Clostridium butyricum was significantly increased by UV stress without supplementation. GTE supplementation helped the skin metabolome defend against UV stress. Interestingly, a significant positive correlation was observed between caecum bacteria (Bifidobacteria, Lactobacillus spp.) and metabolites including skin barrier function-related skin metabolites, caecal fatty acids, and caecal amino acids. Overall, 7-day GTE supplementation was sufficient to alter the gut microbiota and endogenous caecum/skin metabolome, with positive effects on UV stress response, providing insight into the mechanism of the prebiotic effects of GTE supplementation.

Natural compounds could be a complementary alternative to inflammatory bowel disease (IBD) management. This study determined the effects of an aqueous extract of Myrciaria jaboticaba peel (EJP) (50 g L -1 ) on 2,4,6-trinitrobenzenesulfonic acid-induced colitis. Wistar rats were randomized into five groups: HC-healthy control, CC-colitis control, DC-drug control, SJ-short-term treatment with EJP, and LJ-long-term treatment with EJP. The EJP treatments reduced body weight loss, stool consistency score, and spleen enlargement. Gut microbiota was modulated through increased Lactobacillus and Bifidobacterium counts after EJP treatment. Short-chain fatty acids were also higher in the EJP treatment groups. The antioxidant enzyme activities were greater than CC or DC controls. Myeloperoxidase activity (LJ), inducible nitric oxide synthase (LJ/SJ), and intercellular adhesion molecule (SJ) levels were lower than in the CC group. EJP decreased histological scoring, mucosal thickness, and preserved the crypts and histological structure. Therefore, EJP showed beneficial effects and could be potentially used as an adjuvant in IBD treatment.

Non-steroidal anti-inflammatory drugs (NSAIDs) cause damage in the small intestine in a bacteria-dependent manner. As high-fat diet (HFD) is a potent inducer of gut dysbiosis, we investigated the effects of HFD on bacterial flora in the small intestine and NSAID-induced enteropathy. 16S rRNA gene analysis revealed that the population of Bifidobacterium spp. significantly decreased by fold change of individual operational taxonomic units in the small intestine of mice fed HFD for 8 weeks. HFD increased intestinal permeability, as indicated by fluorescein isothiocyanate-dextran absorption and serum lipopolysaccharide levels, accompanied by a decrease in the protein expressions of ZO-1 and occludin and elevated mRNA expression of interleukin (IL)-17A in the small intestine. HFD-fed mice exhibited increased susceptibility to indomethacin-induced damage in the small intestine; this phenotype was observed in normal diet-fed mice that received small intestinal microbiota from HFD-fed mice. Administration of neutralizing antibodies against IL-17A to HFD-fed mice reduced intestinal permeability and prevented exacerbation of indomethacin-induced damage. Thus, HFD-induced microbial dysbiosis in small intestine caused microinflammation through the induction of IL-17A and increase in intestinal permeability, resulting in the aggravation of NSAID-induced small intestinal damage.

Our experiment was to study the effect of high molecular mass ferulic acid sugar ester (HFASE) from corn bran on proliferation of intestinal bifidobacteria in aged mice induced by D-galactose. The number of bifidobacteria in the intestine of D-galactose-induced aging mice was lower than that of normal mice. After the intragastric administration of different doses of HFASE (100, 200, and 300 mg kg -1  day -1 body weight) in experimental groups, the number of bifidobacteria was also higher than the aging group. The proliferation rate of bifidobacteria in the intestine of the experimental groups was fast in the first 24 days of feeding and then tended to be gentle. The H-l experimental group (100 mg/kg body weight) had the most obvious effect of the proliferation of bifidobacteria. PRACTICAL APPLICATIONS: As the by-product of corn starch processing, corn bran was usually processed into animal feed and sold at a low price. The results of this study indicated that high molecular mass corn bran ferulic acid sugar ester had the effect of promoting the proliferation of bifidobacteria in aging mice, which provided ideas for the development and application of corn bran in the food industries. It could be added as a raw material for functional foods to common foods such as yogurt, baked bread, cereals, and porridge., (© 2019 Wiley Periodicals, Inc.)

Two by-products containing phenols and polysaccharides, a "pâté" (OP) from the extra virgin olive oil milling process and a decoction of pomegranate mesocarp (PM), were investigated for their effects on human microbiota using the SHIME ® system. The ability of these products to modulate the microbial community was studied simulating a daily intake for nine days. Microbial functionality, investigated in terms of short chain fatty acids (SCFA) and NH 4 + , was stable during the treatment. A significant increase in Lactobacillaceae and Bifidobacteriaceae at nine days was induced by OP mainly in the proximal tract. Polyphenol metabolism indicated the formation of tyrosol from OP mainly in the distal tract, while urolithins C and A were produced from PM, identifying the human donor as a metabotype A. The results confirm the SHIME ® system as a suitable in vitro tool to preliminarily investigate interactions between complex botanicals and human microbiota before undertaking more challenging human studies., Competing Interests: The authors declare no conflict of interest.

Fructooligosaccharides (FOS) are considered prebiotics and have been proven to selectively promote the growth of Bifidobacterium in the gut. This study aimed to clarify the effects of FOS intake on the composition of luminal and mucosal microbiota in mice. Briefly, mice were fed a 0% or 25% FOS ( w / w )-supplemented diet for four weeks, and the composition of luminal and mucosal microbiota, especially the Bifidobacterium, was analyzed by sequencing the V3-V4 region of 16S rRNA and groEL gene, respectively. After FOS intervention, there were significant increases in the total and wall weights of the cecum and the amount of total short-chain fatty acids (SCFAs) in the cecal contents of the mice. At the phylum level, the results showed a significant increase in the relative abundance of Actinobacteria in the contents and mucosa from the cecum to the distal colon in the FOS group. Besides Bifidobacterium , a significant increase was observed in the relative abundance of Coprococcus in all samples at the genus level, which may be partially related to the increase in butyric acid levels in the luminal contents. Furthermore, groEL sequencing revealed that Bifidobacterium pseudolongum was almost the sole bifidobacterial species in the luminal contents (>98%) and mucosa (>89%). These results indicated that FOS can selectively promote B. pseudolongum proliferation in the intestine, either in the lumen or the mucosa from the cecum to the distal colon. Further studies are required to reveal the competitive advantage of B. pseudolongum over other FOS-metabolizing bacteria and the response mechanisms of B. pseudolongum to FOS.

Globe artichoke is an intriguing source of indigestible sugar polymers such as inulin-type fructans. In this study, the effect of ultrasound in combination with ethanol precipitation to enhance the extraction of long chain fructans from artichoke wastes has been evaluated. The inulin-type fructans content both from bracts and stems was measured using an enzymatic fructanase-based assay, while its average degree of polymerization (DP) was determined by HPLC-RID analysis. Results show that this method provides artichoke extracts with an inulin-type fructans content of 70% with an average DP between 32 and 42 both in bracts and in stems. The prebiotic effect of long chain inulins from artichoke extract wastes was demonstrated by its ability to support the growth of five Lactobacillus and four Bifidobacterium species, previously characterized as probiotics. Besides, we considered the possibility to industrialize the process developing a simpler method for the production of inulin-type fructans from the artichoke wastes so that the artichoke inulin preparation could be suitable for its use in synbiotic formulations in combination with different probiotics for further studies including in vivo trials., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Zahraa Zeaiter et al.)

Hop cones ( Humulus lupulus L.) have been used throughout history as an additive in beer brewing and as herbal supplements with medicinal and culinary properties. The objective of this study was to ascertain the effect of a range of concentrations of a supercritical CO 2 extract of hops on the composition and metabolism of human gut bacterial communities using in vitro batch culture systems. Fermentations were conducted over 24 h using a mixed human fecal inoculum. Microbial metabolism was assessed by measuring organic acid production and microbial community alterations were determined by 16S rRNA gene sequencing. Butyrate, an important short chain fatty acid in maintaining colonic well-being, decreased at elevated concentrations of hops, which may partly be accounted for by the concomitant reduction of Eubacterium and Coprococcus , known butyrate-producing genera, and also the inhibition of Bifidobacterium , a beneficial organism that has a butyrogenic effect through metabolic cross-feeding with intestinal commensals. The hops compounds also caused dose-dependent increases in the potentially pathogenic Enterobacteriaceae and potentially beneficial Akkermansia . Thus, hops compounds had a significant impact on the structure of the bacterial consortium, which warrants further study including human clinical trials., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Increasing awareness of the importance of a healthy Bifidobacterium -rich microbiome has led to a need for more knowledge on how different prebiotic carbohydrates specifically impact the infant microbiome, especially as a community instead of single bacterial targets. In this study, we combined proton nuclear magnetic resonance ( 1 H NMR) metabolomics and molecular biology methods for quantification of bacteria to compare the prebiotic effect of bovine milk oligosaccharides (BMO) and synthetic galacto oligosaccharides (GOS) using mono- and cocultures of eight major bacteria related to a healthy infant microbiome. The results revealed that BMO treatments supported growth of Bifidobacterium longum subsp. longum and Parabacteroides distasonis , while at the same time growth of Clostridium perfringens and Escherichia coli was inhibited. In addition, there was a synergistic effect of combining lactose and BMO in regards to reducing C. perfringens , maintaining stable numbers of P. distasonis and simultaneously increasing numbers of the beneficial B. longum subsp. longum . These results indicate that the oligosaccharide composition plays a vital role in shaping the developing microbiota.

This study aimed to investigate the effect of putrescine on the immune function and intestinal bacteria of weaning piglets. Twenty-four male castrated weaning piglets on their 21st day were randomly assigned into four groups: control (basal diet) and treatment groups given basal diets supplemented with 0.05%, 0.1%, and 0.15% putrescine for 11 days. Results were as follows: (1) Dietary putrescine increased the villus height, width, height/crypt depth and surface area, and decreased the diarrhea index (P < 0.05). (2) Dietary putrescine increased the lysozyme and acid phosphatase activities and the amount of immunoglobulin M, antibacterial peptides, and transforming growth factor β1, but decreased the mRNA levels of tumor necrosis factor α, interleukin-6, interleukin-8 and inducible nitric oxide synthase (P < 0.05). (3) Dietary putrescine increased the mRNA expression of the mammalian target of rapamycin, signal transducer and activator of transcription, and Janus kinase 2 but decreased the mRNA expression of nuclear factor-kappa B P65 (P < 0.05). (4) Dietary putrescine increased the population of total bacteria, Lactobacillus, and Bifidobacterium and decreased that of Escherichia coli in the colon and cecum (P < 0.05). (5) Finally, dietary putrescine increased the concentrations of butyrate and total volatile fatty acids in the colon and those of acetate, propionate, and total volatile fatty acids in the cecum (P < 0.05). Overall, putrescine can enhance intestinal development, improve immune functions, and regulate the population of intestinal bacteria in weaning piglets.

The efficacy of probiotic health products depends on the capability of the constituent probiotic bacteria to survive through long period of cold storage and the gastrointestinal tract. This study was to evaluate the protective effects of a high-molecular weight (MW) exopolysaccharide (EPS) from a medicinal fungus Cs-HK1 on three different bifidobacteria. The EPS had a total dietary fiber content about 70% (w/w), which was close to its total carbohydrate content. It was resistant to artificial gastric acid (pH 2) with no more than 4% (w/w) hydrolysis in 6 h. EPS at 5 g/L significantly increased the survival rate of the probiotic bacteria during cold storage (4 °C) and in simulated gastric acid, reducing the death rate of different bacterial strains by 50% to 70%. The protective effect of EPS was weaker when the concentration was decreased to 3 g/L or when the MW of EPS was reduced by partial degradation with power ultrasound. EPS also showed significantly protective effect on the all bacterial strains in bile juice. The results have demonstrated the potential value of Cs-HK1 EPS as a novel prebiotic fiber for the formulation of synbiotic products with probiotic bacteria., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Probiotics is a prevalence therapeutic method for irritable bowel syndrome (IBS), but there is lack of comparison in different protocols. We aim to differentiate the reasonable protocols by assessing the efficacy and safety through the combined way of traditional and network meta-analysis., Method: PubMed, Medline, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched from January 2006 to April 2019. The relative risk (RR) with a 95% confidence interval (CI) was used to combine dichotomous data of responders., Result: Among 14 studies included 1695 patients were identified as suitable for inclusion. The proportion of responders was associated with the administration of multispecies probiotics (RR: 1.39; 95% CI: 1.19-1.61) and the dose of 10∼10 (RR: 2.08; 95% CI: 1.59-2.71). In network meta-analysis, the protocol of DUO had a significant effect for diarrhea type of IBS compared with placebo (RR: 7.46; 95% CI: 2.00-32.23). In the rest of 4 protocols, no significant difference was found in each other except F19 which appears inferior when compared with Pro (RR: 0.16; 95% CI: 0.03-0.88). Meanwhile, Pro showed a superior effect for undifferentiated-type IBS compared with placebo (RR: 7.16; 95% CI: 1.72-29.89). No probiotics-associated severe adverse event was reported in included studies., Conclusion: Probiotics is a safety choice to improve the overall symptoms for IBS patient. The protocols with suitable dose combined of Lactobacillus and Bifidobacterium can have prepotent effects compared with single species or over-dosage protocols. Network meta-analysis shows that DUO may be the first recommendation for diarrhea-type IBS. In the remaining 4 regimes of this study, Pro has a high rank for undifferentiated-type IBS.

We aimed at isolating and characterising microorganisms present in human breast milk with probiotic potential. In an 8-week postpartum sampling period, two strains of bifidobacteria (Bifidobacterium longum LM7a and Bifidobacterium dentium LM8a') and four strains of lactobacilli were isolated, all during the first 4-week postpartum. B. longum LM7a and B. dentium LM8a', together with four strains previously isolated from breast milk (Bifidobacterium lactis INL1, INL2, INL4 and INL5), were considered for further studies. Susceptibility of the strains to tetracycline, erythromycin, clindamycin, streptomycin, vancomycin and chloramphenicol was evaluated and the isolates exhibited, in general, the same properties as previously reported for bifidobacteria. All isolates showed low hydrophobicity and B. lactis and B. longum strains had satisfactory resistance to gastric digestion and bile shock, but not to pancreatin. B. lactis INL1, B. longum LM7a and B. dentium LM8a' were selected for some comparative technological studies. In particular, B. lactis INL1 displayed technological potential, with satisfactory growth in cheese whey-based media in biofermentor and resistance to freeze-drying, accelerated storage conditions and simulated gastric digestion.

Dragon fruit oligosaccharide (DFO) has a prebiotic property which improves gut health by selectively stimulating the colonic microbiota. Altering microbiota composition may affect intestinal motility. However, no study has been done to understand the DFO effects on gut motor functions. This research thus aimed to investigate the DFO effects on mice colons compared to the prebiotic fructo-oligosaccharide (FOS) and probiotic bifidobacteria. The mice in this study received distilled water; 100, 500, and 1000 mg/kg DFO; 1000 mg/kg FOS; or 10 9 CFU Bifidobacterium animalis daily for 1 week and some treatments for 2 weeks. Gastrointestinal transits were analysed and motility patterns, smooth muscle (SM) contractions and morphological structures of the colons were assessed. Administration of FOS, 500 and 1000 mg/kg DFO significantly increased fecal output when compared to the control group. In mice treated with FOS and bifidobacteria, gut transit time was reduced, while upper gut transit was increased in comparison to DFO groups. Spatiotemporal maps of colonic wall motions showed that DFO increased the number of colonic non-propagation contractions and fecal pellet velocity, consistent with the results from groups treated with FOS and bifidobacteria. DFO also increased the amplitude and duration of colonic SM contractions. Histological stains showed normal epithelia, crypts, goblet cells, and SM thickness in all groups. In conclusion, DFO increased colonic SM contractions without morphological change and acted as a bulk-forming and stimulant laxative to increase fecal output and intestinal motility. Thus, DFO as a dietary supplement may promote gut health and correct gastrointestinal motility disorders., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Infancy is a crucial period for establishing the intestinal microbiome. This process may be influenced by vitamin A (VA) status because VA affects intestinal immunity and epithelial integrity, factors that can, in turn, modulate microbiome development., Objectives: The aim of this study was to determine if neonatal VA supplementation (VAS) affected the abundance of Bifidobacterium, a beneficial commensal, or of Proteobacteria, a phylum containing enteric pathogens, in early (6-15 wk) or late (2 y) infancy. Secondary objectives were to determine if VAS affected the abundance of other bacterial taxa, and to determine if VA status assessed by measuring plasma retinol was associated with bacterial abundance., Methods: Three hundred and six Bangladeshi infants were randomized by sex and birthweight status (above/below median) to receive 1 VA dose (50,000 IU) or placebo within 48 h of birth. Relative abundance at the genus level and above was assessed by 16S rRNA gene sequencing. A terminal restriction fragment-length polymorphism assay was used to identify Bifidobacterium species and subspecies at 6 wk., Results: Linear regression showed that Bifidobacterium abundance in early infancy was lower in boys (median, 1st/3rd quartiles; 0.67, 0.52/0.78) than girls (0.73, 0.60/0.80; P = 0.003) but that boys receiving VAS (0.69, 0.55/0.78) had higher abundance than boys receiving placebo (0.65, 0.44/0.77; P = 0.039). However this difference was not seen in girls (VAS 0.71, 0.54/0.80; placebo 0.75, 0.63/0.81; P = 0.25). VAS did not affect Proteobacteria abundance. Sex-specific associations were also seen for VA status, including positive associations of plasma retinol with Actinobacteria (the phylum containing Bifidobacterium) and Akkermansia, another commensal with possible health benefits, for girls in late infancy., Conclusions: Better VA status in infancy may influence health both in infancy and later in life by promoting the establishment of a healthy microbiota. This postulated effect of VA may differ between boys and girls. This trial was registered at clinicaltrials.gov as NCT02027610., (Published by Oxford University Press on behalf of the American Society for Nutrition 2019.)

Iron supplements are widely consumed; however most of the iron is not absorbed and enters the colon where potentially pathogenic bacteria can utilise it for growth. This study investigated the effect of iron availability on human gut microbial composition and function using an in vitro colonic fermentation model inoculated with faecal microbiota from healthy adult donors, as well as examining the effect of iron on the growth of individual gut bacteria . Batch fermenters were seeded with fresh faecal material and supplemented with the iron chelator, bathophenanthroline disulphonic acid (BPDS). Samples were analysed at regular intervals to assess impact on the gut bacterial communities. The growth of Escherichia coli and Salmonella typhimurium was significantly impaired when cultured independently in iron-deficient media. In contrast, depletion of iron did not affect the growth of the beneficial species, Lactobacillus rhamnosus, when cultured independently. Analysis of the microbiome composition via 16S-based metataxonomics indicated that under conditions of iron chelation, the relative abundance decreased for several taxa, including a 10% decrease in Escherichia and a 15% decrease in Bifidobacterium. Metabolomics analysis using 1 H-NMR indicated that the production of SCFAs was reduced under iron-limited conditions. These results support previous studies demonstrating the essentiality of iron for microbial growth and metabolism, but, in addition, they indicate that iron chelation changes the gut microbiota profile and influences human gut microbial homeostasis through both compositional and functional changes., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Supplementing kindergarten children during a cold season with a prebiotic inulin-type fructans product with shorter and longer fructan chains has been shown to reduce febrile episodes requiring medical attention and to lower the incidence of sinusitis. These beneficial effects may be connected to the specific modulation of children's gut microbiota. By applying quantitative and qualitative microbiota analysis this study aimed at characterising the gut microbiota composition and at exploring effects of prebiotic intervention on the gut microbiota during a 24-weeks intervention and during antibiotic treatment in healthy children. The study was a randomised, placebo-controlled trial with 258 healthy children aged 3 to 6 years consuming 6 g/day prebiotic inulin-type fructans or maltodextrin. During the course of the study, faecal samples were collected and subject to targeted qPCR analysis and phylogenetic profiling by multiplexed high throughput sequencing of the prokaryotic 16S rRNA gene PCR amplicons. The microbiota composition of the cohort could be clustered into three distinct constellations (enterotypes). Prebiotic intake resulted in a selective modulation of the gut microbiota composition. Relative abundance of Bifidobacterium was significantly higher in the prebiotic group (n=104) compared to control group (n=105) and this effect was found for all three enterotypes. Antibiotic administration decreased the relative abundance of Bifidobacterium in both groups. Nonetheless, children of the prebiotic group receiving antibiotic treatment displayed significantly higher levels of Bifidobacterium than children receiving the placebo control. Prebiotic supplementation induced specific changes in the gut microbiota composition of children aged 3 to 6 years. Moreover, it attenuated antibiotic-induced disturbances in the gut microbiota composition as shown by higher relative abundance of bifidobacteria at the end of the antibiotic treatment in the prebiotic group. With the previously reported benefits on immune function, the study contributes to the evidence on the immune-modulating effects of prebiotics through gut microbiota modifications. The study was registered as NCT03241355 ( https://clinicaltrials.gov/show/NCT03241355 ).

The development of prebiotic fibers requires fast high-throughput screening of their effects on the gut microbiota. We demonstrated the applicability of a mictotiter plate in the in vitro fermentation models for the screening of potentially-prebiotic dietary fibers. The effects of seven rye bran-, oat- and linseed-derived fiber preparations on the human fecal microbiota composition and short-chain fatty acid production were studied. The model was also used to study whether fibers can alleviate the harmful effects of amoxicillin-clavulanate on the microbiota. The antibiotic induced a shift in the bacterial community in the absence of fibers by decreasing the relative amounts of Bifidobacteriaceae, Bacteroidaceae, Prevotellaceae, Lachnospiraceae and Ruminococcaceae, and increasing proteobacterial Sutterilaceae levels from 1% to 11% of the total microbiota. The fermentation of rye bran, enzymatically treated rye bran, its insoluble fraction, soluble oat fiber and a mixture of rye fiber:soluble oat fiber:linseed resulted in a significant increase in butyrate production and a bifidogenic effect in the absence of the antibiotic. These fibers were also able to counteract the negative effects of the antibiotic and prevent the decrease in the relative amount of bifidobacteria. Insoluble and soluble rye bran fractions and soluble oat fiber were the best for controlling the level of proteobacteria at the level below 2%., Competing Interests: The authors declare no conflict of interest. The funding organization had no role in the design and execution if this study.

Effects of the microbiome associated with diarrhea-predominant irritable bowel syndrome (IBS-D) on the gut have been reported, but no study has reported the effects of the IBS-D gut microbiome on the liver. We transplanted the fecal microbiota from an IBS-D patient and from a healthy volunteer to GF rats. The hepatic inflammation, serum biochemical parameters and metabolome, fecal microbiota profile, fecal short-chain fatty acids (SCFAs), and correlations among them before and after berberine intervention were assessed. Compared with the healthy control fecal microbiome transplantation (FMT) rats, the fecal microbiota of IBS-D patients induces significant Kupffer cell hyperplasia, hepatic sinusoid hypertrophy, and elevated levels of hepatic tumor necrosis factor- α and interferon- γ and decreases the synthesis of ALB in GF rats. This is possibly related to Faecalibacterium and Bifidobacterium attributable to fecal formate, acetate, and propionate levels, which are associated with the host linoleic acid pathway. Berberine can partially reverse the Kupffer cell hyperplasia, Faecalibacterium , fecal formate, acetate, and propionate by modulating the gut microbiome composition. These results may imply that IBS-D not only is an intestinal functional disorder but can cause liver inflammation, thus providing some implications regarding the clinical cognition and treatment of IBS-D.

Human milk is an important source of microorganisms for infant gut colonisation. Although the maternal antibiotic prophylaxis is an important strategy to prevent maternal/neonatal sepsis, it has to be investigated how it may affect the human milk microbiota, especially the genus Bifidobacterium, which has been associated to health benefits. Here, we investigated the impact of the maternal antibiotic prophylaxis on the human milk Bifidobacterium spp. and total bacteria counts, in the first week (short-term) and first month (medium-term) after delivery. Human milk samples were collected from 55 healthy lactating women recruited from the University Hospital of the University of São Paulo at days 7±3 and 30±4 after vaginal delivery. Twenty one volunteers had received maternal antibiotic prophylaxis (MAP group) and 34 had not received MAP (no-MAP group) during or after labour. Total DNA was isolated from milk samples, and the bacterial counts were estimated by quantitative PCR (qPCR). We found lower levels of Bifidobacterium in the MAP group in the first week after delivery (median = 2.1 vs 2.4 log of equivalent cells/ml of human milk, for MAP and no-MAP groups, respectively; P=0.01), although there were no statistical differences in total bacteria count. However, no differences were found in Bifidobacterium counts between the groups at day 30±4 (median = 2.5 vs 2.2 log of equivalent cells/ml of human milk, for MAP and no-MAP groups, respectively; P=0.50). Our results suggest that MAP has a significant impact on Bifidobacterium counts in human milk, reducing this population in the first week after delivery. However, throughout the first month after delivery, the Bifidobacterium counts tend to recover, reaching similar counts to those found in no-MAP group at day 30±4 after delivery.

Environment and diet are key factors which shape the microbiome of organisms. There is also a disparity between captive and wild animals of the same species, presumably because of the change in diet. Being able to reverse the microbiome to the wild type is thus particularly important for the reintroduction efforts of Critically Endangered animals. The Javan slow loris (Nycticebus javanicus) is a suitable model, being kept in the thousands within rescue centres throughout Southeast Asia. With next-generation sequencing, we show how a naturalistic diet impacts the gut microbiome of captive slow lorises (Primates: Nycticebus). A comparison of the microbiome of wild animals with captive animals that had been fed a standard captive or improved diet reveals strong microbiome differences between wild and captive animals; however, diet changes failed to alter the microbiome of captive populations significantly. Bifidobacterium was the most abundant genus in wild animals (46.7%) while Bacteroides (11.6%) and Prevotella (18.9%) were the most abundant in captive animals fed the captive and improved diets, respectively. Correlation analyses of nutrients with microbial taxa suggest important implications in using nutrition to suppress potential pathogens, with soluble fibre and water-soluble carbohydrates both being associated with opposing microbiome profiles. The improved diet significantly increased microbe diversity, which exemplifies the importance of high fibre diets; however, wild individuals had lower diversity, which contradicts recent studies. Detection of methanogens appeared to be dependent on diet and whether the animals were living in captivity or in the wild. This study highlights the potential of nutrition in modulating the microbiome of animals prior to release. Unexpectedly, the results were not as significant as has been suggested in recent studies.

Wholegrain oats are known to modulate the human gut microbiota and have prebiotic properties (increase the growth of some health-promoting bacterial genera within the colon). Research to date mainly attributes these effects to the fibre content; however, oat is also a rich dietary source of polyphenols, which may contribute to the positive modulation of gut microbiota. In vitro anaerobic batch-culture experiments were performed over 24 h to evaluate the impact of two different doses (1 and 3 % (w/v)) of oat bran, matched concentrations of β-glucan extract or polyphenol mix, on the human faecal microbiota composition using 16S RNA gene sequencing and SCFA analysis. Supplementation with oats increased the abundance of Proteobacteria (P &lt;0·01) at 10 h, Bacteroidetes (P &lt;0·05) at 24 h and concentrations of acetic and propionic acid increased at 10 and 24 h compared with the NC. Fermentation of the 1 % (w/v) oat bran resulted in significant increase in SCFA production at 24 h (86 (sd 27) v. 28 (sd 5) mm; P &lt;0·05) and a bifidogenic effect, increasing the relative abundance of Bifidobacterium unassigned at 10 h and Bifidobacterium adolescentis (P &lt;0·05) at 10 and 24 h compared with NC. Considering the β-glucan treatment induced an increase in the phylum Bacteroidetes at 24 h, it explains the Bacteriodetes effects of oats as a food matrix. The polyphenol mix induced an increase in Enterobacteriaceae family at 24 h. In conclusion, in this study, we found that oats increased bifidobacteria, acetic acid and propionic acid, and this is mediated by the synergy of all oat compounds within the complex food matrix, rather than its main bioactive β-glucan or polyphenols. Thus, oats as a whole food led to the greatest impact on the microbiota.

The development of gut microbiota during infancy is an important event that affects the health status of the host; however, the mechanism governing it is not fully understood. l-Amino acid oxidase 1 (LAO1) is a flavoprotein that catalyzes the oxidative deamination of particular l-amino acids and converts them into keto acids, ammonia, and H 2 O 2 . Our previous study showed that LAO1 is present in mouse milk and exerts protection against bacteria by its production of H 2 O 2 . The data led us to consider whether LAO1, H 2 O 2 , or both could impact infant gut microbiota development via mother's milk consumption in mice. Different gut microbiota profiles were observed in the wild-type (WT) and LAO1-knockout mouse pups. The WT pups' microbiota was relatively simple and composed of only a few dominant bacteria, such as Lactobacillus, whereas the lactating knockout pups had high microbiota diversity. Cross-fostering experiments indicated that WT milk (containing LAO1) has the ability to suppress the diversity of microbiota in pups. We observed that the stomach content of pups fed WT milk had LAO1 proteins and the ability to produce H 2 O 2 . Moreover, culture experiments showed that Lactobacillus was abundant in the feces of pups fed WT milk and that Lactobacillus was more resistant to H 2 O 2 than Bifidobacterium and Escherichia. Human breast milk produces very little H 2 O 2 , which could be the reason for Lactobacillus not being dominant in the feces of breast-fed human infants. In mouse mother's milk, H 2 O 2 is generated from the process of free amino acid metabolism, and H 2 O 2 may be a key player in regulating the initial acquisition and development of gut microbiota, especially growth of Lactobacillus, during infancy.-Shigeno, Y., Zhang, H., Banno, T., Usuda, K., Nochi, T., Inoue, R., Watanabe, G., Jin, W., Benno, Y., Nagaoka, K. Gut microbiota development in mice is affected by hydrogen peroxide produced from amino acid metabolism during lactation.

Background: Evidence has shown that anthocyanins, a subclass of polyphenol, are metabolised in the gut, modulate bacterial species and exert bioactive effects through this interaction., Methods: A systematic literature review was undertaken to determine the level of current evidence for the association between anthocyanin intake and changes in gut microbiota populations. The studies included were also assessed for the different techniques used in microbiota determination. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, scientific databases, including Scopus, PubMed, ScienceDirect, Web of Science and MEDLINE, were searched up to June 2017. Details on population/sample, study design, intervention/control, dosage and method of microbiota determination were extracted., Results: Six studies (three in vitro, two animal and one human trials) were included in the review, which showed that anthocyanins induced a significant proliferative effect on Bifidobacterium spp., known for their wide use in probiotics and for the treatment of irritable bowel syndrome. There was also an observed inhibition of Clostridium histolyticum, which was shown to be pathogenic in humans. The depth of analysis is an important consideration for the choice of microbiota determination technique with respect to a comprehensive, high-resolution microbiota analysis or analysis of the main microbiota taxa., Conclusions: Very limited research has been carried out in the area of anthocyanins and gut microbiota; beneficial effects have generally been observed, and further clinical trials in humans are needed to confirm changes to gut microbes in relation to dietary anthocyanin intake and potential health benefits., (© 2018 The British Dietetic Association Ltd.)

Background: The intestinal microbiome in early infancy affects immunologic development and thus may affect vaccine memory, though few prospective studies have examined such associations. We examined the association of Bifidobacterium levels in early infancy with memory responses to early vaccination measured at 2 years of age., Methods: In this prospective observational study, we examined the association of Bifidobacterium abundance in the stool of healthy infants at 6 to 15 weeks of age, near the time of vaccination, with T-cell and antibody responses measured at 6 weeks, 15 weeks, and 2 years of age. Infants were vaccinated with Bacillus Calmette-Guérin (BCG) (at birth), oral polio virus (at birth and at 6, 10, and 14 weeks), tetanus toxoid (TT) (at 6, 10, and 14 weeks), and hepatitis B virus (at 6, 10, and 14 weeks). Fecal Bifidobacterium was measured at 6, 11, and 15 weeks. Bifidobacterium species and subspecies were measured at 6 weeks., Results: Mean Bifidobacterium abundance in early infancy was positively associated with the CD4 T-cell responses to BCG, TT, and hepatitis B virus at 15 weeks, with CD4 responses to BCG and TT at 2 years, and with plasma TT-specific immunoglobulin G and stool polio-specific immunoglobulin A at 2 years. Similar associations were seen for the predominant subspecies, Bifidobacterium longum subspecies infantis ., Conclusions: Bifidobacterium abundance in early infancy may increase protective efficacy of vaccines by enhancing immunologic memory. This hypothesis could be tested in clinical trials of interventions to optimize Bifidobacterium abundance in appropriate populations., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Underwood’s institution (University of California, Davis) has received grant support from Evolve Biosystems to fund a clinical trial of a probiotic in term infants; he has consulted for Avexegen and received payment for travel and lectures from Abbott. Dr Mills is a cofounder of and consultant for Evolve Biosystems and has stock and stock options therein; he has received payment for lectures from Nestle and Abbott; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Ingestion of bioactive compounds, such as hesperidin and naringin, found in citrus fruits and orange juice, can improve the homeostasis of gut microbiota. A controlled clinical study with temporal series intergroup design with 10 apparently healthy women (28.5 ± 8.4 years, 24.1 ± 3.3 kg/m 2 ) were evaluated after continuous consumption of commercial pasteurized orange juice for 2 months. Samples of blood serum and stool were collected at basal time and periodically during the experiment for biochemical and microbiology assays. Intestinal microbiota was evaluated for total anaerobic bacteria, Lactobacillus spp., Bifidobacterium spp., and Clostridium spp. An independent culture evaluation was performed using Denaturing Gradient Gel Electrophoresis (DGGE). The pH, ammonium (NH 4 + ), and short-chain fatty acids (SCFAs) were evaluated for microbial metabolism. The results showed that daily intake of orange juice did not change women's body composition, but improved blood biochemical parameters, such as low-density lipoprotein-cholesterol, glucose, and insulin sensitivity. Orange juice positively modulated the composition and metabolic activity of microbiota, increasing the population of fecal Bifidobacterium spp. and lactobacillus spp. Polymerase chain reaction-DGGE of microbiota showed similar composition of total bacteria, and microbial metabolism showed a reduction of ammonia and an increase of the production of SCFAs. These results suggested that a daily consumption of orange had a positive effect on the intestinal microbiota and metabolic biomarkers of young women, which may be an effective alternative for a healthy drink.

Phages, the most abundant species in the mammalian gut, have numerous advantages as biocontrol agent over antibiotics. In this study, mice were orally treated with the lytic gut phage PA13076 (group B), the temperate phage BP96115 (group C), no phage (group A), or streptomycin (group D) over 31 days. At the end of the experiment, fecal microbiota diversity and composition was determined and compared using high-throughput sequencing of the V3-V4 hyper-variable region of the 16S rRNA gene and virus-like particles (VLPs) were quantified in feces. There was high diversity and richness of microbiota in the lytic and temperate gut phage-treated mice, with the lytic gut phage causing an increased alpha diversity based on the Chao1 index (p < 0.01). However, the streptomycin treatment reduced the microbiota diversity and richness (p = 0.0299). Both phage and streptomycin treatments reduced the abundance of Bacteroidetes at the phylum level (p < 0.01) and increased the abundance of the phylum Firmicutes. Interestingly, two beneficial genera, Lactobacillus and Bifidobacterium, were enhanced by treatment with the lytic and temperate gut phage. The abundance of the genus Escherichia/Shigella was higher in mice after temperate phage administration than in the control group (p < 0.01), but lower than in the streptomycin group. Moreover, streptomycin treatment increased the abundance of the genera Klebsiella and Escherichia/Shigella (p < 0.01). In terms of the gut virome, fecal VLPs did not change significantly after phage treatment. This study showed that lytic and temperate gut phage treatment modulated the composition and diversity of gut microbiota and the lytic gut phage promoted a beneficial gut ecosystem, while the temperate phage may promote conditions enabling diseases to occur.

Statin response shows great interindividual variations. Recently, emerging studies have shown that gut microbiota is linked to therapeutic responses to drugs, including statins. However, the association between the gut bacteria composition and statin response is still unclear. In this study, gut microbiota of 202 hyperlipidemic patients with statin sensitive (SS) response and statin resistant (SR) response in East China were investigated by high throughput sequencing to compare the gut bacteria composition and biodiversity in distinct statin response patients. Higher biodiversity was detected in Group SS than Group SR. Specifically, group SS showed significantly increased proportion of genera Lactobacillus (P = 0.001), Eubacterium (P = 0.004), Faecalibacterium (P = 0.005), and Bifidobacterium (P = 0.002) and decreased proportion of genus Clostridium (P = 0.001) compared to Group SR. The results indicated that higher gut biodiversity was associated with statin sensitive response. The increased genera Lactobacillus, Eubacterium, Faecalibacterium, Bifidobacterium, and decreased genus Clostridium in patient gut microbiota may predict patient's statin response, and hence may guide statin dosage adjustments.

Objective: Glass ionomer cements (GICs) are a versatile material, offering the opportunity for ion exchange with the oral environment. The aim of this study was to develop a GIC that delivers a controlled, rechargeable dose of chlorhexidine (CHX) over an extended period without compromising mechanical properties., Methods: GICs were supplemented with finely milled particles of chlorhexidine hexametaphosphate (CHX-HMP). CHX release into artificial saliva was measured over 660 days, and recharge with CHX and CHX-HMP was investigated. Mechanical properties were investigated, and an agar diffusion test was carried out to assess antimicrobial properties using Streptococcus mutans and Scardovia wiggsiae., Results: Dose-dependent CHX release was observed, and this was ongoing at 660 days. Compared with related studies of GICs containing CHX-HMP, the fine, dry particles resulted in fewer adverse effects on mechanical properties, including tensile, compressive and biaxial flexural strength, with 1% CHX-HMP GICs indistinguishable from control specimens. The GICs could be recharged with CHX using both a conventional CHX digluconate solution comparable to commercial mouthrinses, and a suspension of CHX-HMP of equivalent concentration. Recharging with CHX digluconate increased subsequent CHX release by 50% compared with no recharge, and recharging with CHX-HMP increased subsequent CHX release by 100% compared with no recharge. The GICs inhibited growth of St. mutans and Sc. wiggsiae in a simple agar diffusion model., Significance: These materials, which provide sustained CHX release over clinically relevant timescales, may find application as a restorative material intended to inhibit secondary caries as well as in temporary restorations and fissure sealants., (Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Dietary fiber stimulates the growth of potentially beneficial bacteria (eg, bifidobacteria), yet most Americans do not meet daily fiber recommendations. Resistant maltodextrin (RMD), a fermentable functional fiber, may help individuals meet total fiber recommendations and potentially increase bifidobacteria. It was hypothesized that fecal bifidobacteria counts/ng fecal DNA would increase after adding 25 g RMD to inadequate fiber diets of healthy adults. In this double-blind, controlled crossover study, 51 participants (26.3 ± 6.8 years, mean ± SD) were randomized to consume 0, 15, and 25 g RMD daily for 3 weeks followed by a 2-week washout. Participants collected all stools for 2 days at weeks 0 and 3 of each intervention for stool wet weight (WW) measurements and fecal bifidobacteria counts. Weekly 24-hour dietary recalls assessed total fiber intake. Only 25 g RMD resulted in a change (final minus baseline) in bifidobacteria that was significant compared with 0 g (0.17 ± 0.09 vs -0.17 ± 0.09 log 10 [counts], respectively, mean ± SEM, P = .008). Stool WW increased only with 25 g (150 ± 11 vs baseline 121±11 g/d; P = .011). Mean daily total fiber intake (including RMD) was significantly higher (both P< .001) with 15 g (17.8 ± 0.6 g/1000 kcal or 4184 kJ) and 25 g (25.3 ± 1.1 g/1000 kcal) compared with 0 g RMD (8.4±0.4 g/1000 kcal). Mean daily total fiber intakes exceeded recommendations (14 g/1000 kcal) with 15 and 25 g of RMD, and 25 g RMD increased fecal bifidobacteria counts and stool WW, suggesting health benefits from increasing total fiber intake., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study was to assess the protective effect of exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis Cs-HK1 on Bifidobacteria against antibiotic inhibition. The high-molecular weight EPS fractions showed significant protective effect on all five bifidobacterial strains against four common antibiotics, leading to a dramatic increase in the minimal inhibitory and minimal bactericidal concentrations. The protective effect of EPS on the bacteria was probably attributed to the formation of a viscous layer around the bacterial cell resisting the access by the antibiotics. The EPS layer surrounding the bacteria cell also promoted the aggregation of bacteria and formation of biofilm as observed by microscopy. EPS also enhanced the bifidobacterial adhesion to Caco-2 cell monolayer. In general, the protective effect as well as biofilm formation due to EPS was significantly correlated with the molecular weight of EPS fractions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Tart cherries have been reported to exert potential health benefits attributed to their specific and abundant polyphenol content. However, there is a need to study the impact and fate of tart cherries polyphenols in the gut microbiota. Here, tart cherries, pure polyphenols (and apricots) were submitted to in vitro bacterial fermentation assays and assessed through 16S rRNA gene sequence sequencing and metabolomics. A short-term (5 days, 8 oz. daily) human dietary intervention study was also conducted for microbiota analyses. Tart cherry concentrate juices were found to contain expected abundances of anthocyanins (cyanidin-glycosylrutinoside) and flavonoids (quercetin-rutinoside) and high amounts of chlorogenic and neochlorogenic acids. Targeted metabolomics confirmed that gut microbes were able to degrade those polyphenols mainly to 4-hydroxyphenylpropionic acids and to lower amounts of epicatechin and 4-hydroxybenzoic acids. Tart cherries were found to induce a large increase of Bacteroides in vitro, likely due to the input of polysaccharides, but prebiotic effect was also suggested by Bifidobacterium increase from chlorogenic acid. In the human study, two distinct and inverse responses to tart cherry consumption were associated with initial levels of Bacteroides. High-Bacteroides individuals responded with a decrease in Bacteroides and Bifidobacterium, and an increase of Lachnospiraceae, Ruminococcus and Collinsella. Low-Bacteroides individuals responded with an increase in Bacteroides or Prevotella and Bifidobacterium, and a decrease of Lachnospiraceae, Ruminococcus and Collinsella. These data confirm that gut microbiota metabolism, in particular the potential existence of different metabotypes, needs to be considered in studies attempting to link tart cherries consumption and health., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Interest in the consumption of gum acacia (GA) has been associated with beneficial health effects, which may be mediated in part by prebiotic activity. Two doses of GA and fructooligosaccharide (FOS) (1 and 2%) were tested for their efficacy over 48 h in pH- and temperature-controlled anaerobic batch cultures inoculated with human faeces. Samples were taken after 0, 5, 10, 24 and 48 h of fermentation. The selective effects of GA (increases in Bifidobacterium spp. and Lactobacillus spp.) were similar to those of the known prebiotic FOS. The 1% dose of substrates showed more enhanced selectivity compared to the 2% dose. The fermentation of GA also led to SCFA production, specifically increased acetate after 10, 24 and 48 h of fermentation, propionate after 48 h and butyrate after 24 and 48 h. In addition, FOS led to significant increase in the main SCFAs. These results suggest that GA displays potential prebiotic properties.

In the current report, we describe the identification of three genetically distinct groups of prophages integrated into three different chromosomal sites of human gut-associated Bifidobacterium breve and Bifidobacterium longum strains. These bifidobacterial prophages are distantly related to temperate actinobacteriophages of several hosts. Some prophages, integrated within the dnaJ 2 gene, are competent for induction, excision, replication, assembly and lysis, suggesting that they are fully functional and can generate infectious particles, even though permissive hosts have not yet been identified. Interestingly, several of these phages harbor a putative phase variation shufflon (the Rin system) that generates variation of the tail-associated receptor binding protein (RBP). Unlike the analogous coliphage-associated shufflon Min, or simpler Cin and Gin inversion systems, Rin is predicted to use a tyrosine recombinase to promote inversion, the first reported phage-encoded tyrosine-family DNA invertase. The identification of bifidobacterial prophages with RBP diversification systems that are competent for assembly and lysis, yet fail to propagate lytically under laboratory conditions, suggests dynamic evolution of bifidobacteria and their phages in the human gut.

Fructooligosaccharides (FOS) are a well-known class of prebiotic and are considered to selectively stimulate the growth of bifidobacteria in the gut. Previous studies focused on the growth stimulation of Bifidobacterium , but they did not further investigate the bifidobacterial composition and the specific species that were stimulated. In this study, mice were fed with FOS in different doses for four weeks and the composition of fecal microbiota, in particular Bifidobacterium , was analyzed by sequencing the V3⁻V4 region and the groEL gene on the MiSeq platform, respectively. In the high-dose group, the relative abundance of Actinobacteria was significantly increased, which was mainly contributed by Bifidobacterium . At the genus level, the relative abundances of Blautia and Coprococcus were also significantly increased. Through the groEL sequencing, 14 species of Bifidobacterium were identified, among which B. pseudolongum was most abundant. After FOS treatment, B. pseudolongum became almost the sole bifidobacterial species (>95%). B. pseudolongum strains were isolated and demonstrated their ability to metabolize FOS by high performance liquid chromatography (HPLC). Therefore, we inferred that FOS significantly stimulated the growth of B. pseudolongum in mice. Further investigations are needed to reveal the mechanism of selectiveness between FOS and B. pseudolongum , which would aid our understanding of the basic principles between dietary carbohydrates and host health., Competing Interests: The authors declare no conflict of interest.

Background: Intestinal microflora has been shown to play essential roles in the clinical therapies of metabolic diseases. The present study is aiming to investigate the potential roles and mechanisms of how intestinal microflora mediates lipid-reduction efficacy of Rosuvastatin., Methods: To investigate the correlation between the intestinal microflora and efficacy of Rosuvastatin, we analyzed the diversity of intestinal microflora using PCR-DGGE analysis and 16S rDNA sequencing approaches. Furthermore, we compared the blood lipid levels of rat models with dysbiosis of intestinal microflora and control rats upon the Rosuvastatin administration., Results: The diversity of the intestinal flora was obviously decreased upon the antibiotic treatment, this effect could be maintained for 2 weeks after establishment of the models. Importantly, the results from 16S rDNA sequencing demonstrated that the abundance of Lactobacillus and Bifidobacterium was remarkably diminished upon the antibiotic treatment in antibiotic+Rosuvastatin-treated group compared to that of Rosuvastatin-treated group and control group. Correspondently, the lipid-reduction efficacy of Rosuvastatin was significantly compromised. However, the diversity of the intestinal flora was recovered 4 weeks after the antibiotic treatment. Subsequently, the lipid-reduction efficacy of Rosuvastatin was also recovered to level of the control rats treated with Rosuvastatin alone., Conclusion: Intestinal flora could play an essential role in mediating the lipid-reduction efficacy of Rosuvastatin.

Recently, accumulating evidence has suggested that Enteromorpha clathrata polysaccharide (ECP) could contribute to the treatment of diseases. However, as a promising candidate for marine drug development, although ECP has been extensively studied, less consideration has been given to exploring its effect on gut microbiota. In this light, given the critical role of gut microbiota in health and disease, we investigated here the effect of ECP on gut microbiota using 16S rRNA high-throughput sequencing. As revealed by bioinformatic analyses, ECP considerably changed the structure of the gut microbiota and significantly promoted the growth of probiotic bacteria in C57BL/6J mice. However, interestingly, ECP exerted different effects on male and female microbiota. In females, ECP increased the abundances of Bifidobacterium spp. and Akkermansia muciniphila , a next-generation probiotic bacterium, whereas in males, ECP increased the population of Lactobacillus spp. Moreover, by shaping a more balanced structure of the microbiota, ECP remarkably reduced the antigen load from the gut in females. Altogether, our study demonstrates for the first time a prebiotic effect of ECP on gut microbiota and forms the basis for the development of ECP as a novel gut microbiota modulator for health promotion and disease management.

DS-2969b is a novel GyrB inhibitor in development for the treatment of Clostridium difficile infection (CDI). The aim of this study was to assess the safety, tolerability, pharmacokinetics, and effects on the normal gastrointestinal microbiota of multiple daily oral ascending doses of DS-2969b in healthy subjects. The study enrolled three sequential ascending-dose cohorts (60 mg, 200 mg, and 400 mg). In each cohort, subjects received an oral dose of DS-2969b or placebo (six subjects received DS-2969b, and two received placebo) each morning for 14 days. DS-2969b was safe and well tolerated at all dose levels examined. All adverse events related to DS-2969b were mild and predominantly related to the gastrointestinal tract. DS-2969a (free form of DS-2969b) plasma concentrations increased with increasing doses; however, both the maximum concentration of drug in serum ( C max ) and the area under the concentration-time curve (AUC) increased less than dose proportionally. In all cohorts, sufficient fecal levels of DS-2969a were achieved within 24 h following the administration of the first dose and maintained for at least 17 days. Following treatment with DS-2969b, clear reductions in the populations of Clostridium coccoides and Bifidobacterium groups were observed. However, populations of three other bacterial groups examined ( Bacteroides fragilis , Clostridium leptum , and Prevotella ) were not affected. Data from this study support and encourage the further development of DS-2969b as a novel treatment for CDI., (Copyright © 2018 American Society for Microbiology.)

Dietary intake of barley β-glucan (BG) is known to affect energy metabolism. However, its underlying mechanism remains poorly understood because studies have presented inconsistent results, with both positive and negative effects reported in terms of satiety, energy intake, weight loss, and glycemic control. The objective of this study was to clarify the physiological role underlying the metabolic benefits of barley BG using a mouse model of high fat diet (HFD)-induced obesity. Male 4-wk-old C57BL/6J mice were fed an HFD with 20% barley flour containing either high BG (HBG; 2% BG) or low BG (LBG; 0.6% BG) levels under conventional and germ-free (GF) conditions for 12 wks. In addition, mice were fed either an HFD with 5% cellulose (HFC; high fiber cellulose) or 5% barley BG (HFB; high fiber β-glucan) for 12 wks. Then, metabolic parameters, gut microbial compositions, and the production of fecal short-chain fatty acids (SCFAs) were analyzed. The weight gain and fat mass of HBG-fed mice were lower than those of control mice at 16-wk-old. Moreover, the secretion of the gut hormones PYY and GLP-1 increased in HBG-fed mice, thereby reducing food intake and improving insulin sensitivity by changing the gut microbiota and increasing SCFAs (especially, butyrate) under conventional condition. These effects in HBG-fed mice were abolished under GF conditions. Moreover, the HFB diets also increased PYY and GLP-1 secretion, and decreased food intake compared with that in HFC-fed mice. These results suggest that the beneficial metabolic effects of barley BG are primary due to the suppression of appetite and improvement of insulin sensitivity, which are induced by gut hormone secretion promoted via gut microbiota-produced SCFAs.

Anthocyanins are naturally active substances. In this study, anthocyanins from black rice were obtained by membrane filtration and column chromatography separation. Five anthocyanin monomers in black rice extract were identified by HPLC-MS/MS, and the major anthocyanin monomer (cyanidin-3-glucoside, C3G) was purified by preparative HPLC (Pre-HPLC). The proliferative effects of the anthocyanins on Bifidobacteria and Lactobacillus were investigated by determining the media pH, bacterial populations and metabolic products. After anaerobic incubation at 37 °C for 48 h, not only the pH of the media containing C3G was lower than that of the extract of black rice anthocyanin (BRAE), but the numbers of both Bifidobacteria and Lactobacillus were also significantly increased. Furthermore, hydroxyphenylpropionic, hydroxyphenylacetic, and hydroxybenzoic acids and other metabolites were detected by GC-MS in vitro. Our results revealed that the anthocyanins and anthocyanin monomers from black rice had prebiotic activity and they were metabolized into several small molecules by Bifidobacteria and Lactobacillus.

Pectin oligosaccharide (POS) fractions were obtained by controlled chemical degradation of citrus peel pectin. By adjusting trifluoroacetic acid (TFA) concentration, three oligosaccharides were obtained, of molecular weight (Mw) range 3000-4000 Da, 2000-3000 Da and lower than 2000 Da. Varying hydrogen peroxide (H 2 O 2 ) concentration and reaction time produced oligosaccharides of 3000-4000 Da and 2000-3000 Da. The relative proportions of acidic monosaccharide increased from 68.58% to 89.93% (TFA) and from 63.74% to 83.26% (H 2 O 2 ) as the reaction conditions intensified. Prebiotic activity scores were used to quantify POS ability to promote selective growth of specific probiotics. Sample POS H1 from H 2 O 2 degradation showed the highest prebiotic potential with prebiotic activity score 0.41 for Lactobacillus paracasei LPC-37 and 0.92 for Bifidobacterium bifidum ATCC 29521., (Copyright © 2017. Published by Elsevier Ltd.)

We have previously reported that 60% sucrose diet-fed ChREBP knockout mice (KO) showed body weight loss resulting in lethality. We aimed to elucidate whether sucrose and fructose metabolism are impaired in KO. Wild-type mice (WT) and KO were fed a diet containing 30% sucrose with/without 0.08% miglitol, an α-glucosidase inhibitor, and these effects on phenotypes were tested. Furthermore, we compared metabolic changes of oral and peritoneal fructose injection. A thirty percent sucrose diet feeding did not affect phenotypes in KO. However, miglitol induced lethality in 30% sucrose-fed KO. Thirty percent sucrose plus miglitol diet-fed KO showed increased cecal contents, increased fecal lactate contents, increased growth of lactobacillales and Bifidobacterium and decreased growth of clostridium cluster XIVa. ChREBP gene deletion suppressed the mRNA levels of sucrose and fructose related genes. Next, oral fructose injection did not affect plasma glucose levels and liver fructose contents; however, intestinal sucrose and fructose related mRNA levels were increased only in WT. In contrast, peritoneal fructose injection increased plasma glucose levels in both mice; however, the hepatic fructose content in KO was much higher owing to decreased hepatic Khk mRNA expression. Taken together, KO showed sucrose intolerance and fructose malabsorption owing to decreased gene expression., Competing Interests: The authors declare no conflicts of interest.

Background: Non-digestible carbohydrates present in cereals such as fructans and arabinoxylans represent promising prebiotic nutrients to prevent the development of obesity and related metabolic disorders., Objective and Design: The aim of this study was to determine the corrective effects of wheat bran-derived arabinoxylan oligosaccharides in obese mice fed a western diet (WD). WD was given for 4 weeks before wheat bran extract (WBE) supplementation (5%) for an additional 4 weeks, whereas a control group received the standard diet., Results: Bifidogenic effect of WBE was evidenced by an induction of both Bifidobacterium animalis and Bifidobacterium pseudolongum in the caecal content. WBE supplementation normalised WD-induced fat-mass expansion, steatosis, hypercholesterolemia, hyperleptinemia, hyperglycemia and hyperinsulinemia reaching the values of control mice. The reduced glucose-dependent insulinotropic polypeptide (GIP) release observed in WD + WBE mice may be a protective mechanism in terms of reducing adipose tissue storage, hepatic steatosis and glucose homoeostasis., Conclusion: We found that WBE completely abolished WD-induced metabolic disorders. Those results might be useful to take into account nutritional advices to treat obesity and related metabolic disorders such as type 2 diabetes, hypercholesterolaemia and fatty liver diseases when obesity was already established.

Several clinical studies have shown that isoflavones and Lactobacillus casei Shirota (LcS) have beneficial effects on skin condition and the gut microbiota, respectively. Thus, we investigated the effects of consecutive intake of fermented soymilk (FSM) with LcS on skin condition and the gut microbiota, as well as isoflavone bioavailability, in a randomised, double-blind, placebo-controlled trial as a pilot study. Sixty healthy premenopausal Japanese women received FSM containing a moderate level of isoflavone aglycones and a probiotic LcS, or soymilk (SM) containing neither of them, twice a day for 8 weeks. Skin condition was assessed by a subjective questionnaire for face and morphological analysis of the stratum corneum on the inner forearm. Faecal microbiota and urinary isoflavone were analysed by 16S rRNA gene amplicon sequencing and high-performance liquid chromatography tandem mass spectrometry, respectively. Both the FSM and SM groups had improved skin condition as assessed from scores of overall satisfaction, dryness, moisture, elasticity, coarseness, pigmentation and/or stratum corneum morphology, as well as significantly increased levels of urinary isoflavones during the intake period compared with the pre-intake period, although there were no significant differences between the two groups. There was a significant positive correlation between urinary isoflavone levels and skin questionnaire scores. In contrast, the relative abundance levels of Lactobacillaceae significantly increased and those of Bifidobacteriaceae tended to increase during the intake period compared with the pre-intake period. For the after-intake period they only decreased significantly in the FSM group. The levels of Enterobacteriaceae and Porphyromonadaceae significantly decreased during the intake period in the FSM group. These findings suggest that daily intake of FSM, as well as SM, provides health benefits that improve skin condition via increased levels of isoflavone absorption in the body, and that only FSM beneficially modifies the gut microbiota in premenopausal healthy women.