The plant growth-promoting effect of the nitrogen-fixing endophyte Pseudomonas stutzeri A15.

The use of plant growth-promoting rhizobacteria as a sustainable alternative for chemical nitrogen fertilizers has been explored for many economically important crops. For one such strain isolated from rice rhizosphere and endosphere, nitrogen-fixing Pseudomonas stutzeri A15, unequivocal evidence of the plant growth-promoting effect and the potential contribution of biological nitrogen fixation (BNF) is still lacking. In this study, we investigated the effect of P. stutzeri A15 inoculation on the growth of rice seedlings in greenhouse conditions. P. stutzeri A15 induced significant growth promotion compared to uninoculated rice seedlings. Furthermore, inoculation with strain A15 performed significantly better than chemical nitrogen fertilization, clearly pointing to the potential of this bacterium as biofertilizer. To assess the contribution of BNF to the plant growth-promoting effect, rice seedlings were also inoculated with a nitrogen fixation-deficient mutant. Our results suggest that BNF (at best) only partially contributes to the stimulation of plant growth.

Early colonization of functional groups of microbes in the infant gut.

The colonization of the infant gut is crucial for early life development. Although the composition and diversity of the infant gut microbiota (GM) has been well described at a taxonomic level, functional aspects of this ecosystem remain unexplored. In the infant gut, lactate is produced by a number of bacteria and plays an important role in the trophic chain of the fermentation process. However, little is known about the lactate-utilizing bacteria (LUB) community in infants and their impact on gut health. By combining culture-based and molecular methods, we intensively studied LUB in fecal samples of 40 healthy infants on both taxonomic and functional levels. We demonstrated metabolic cross-feeding of lactate and identified keystone species specified for lactate utilization. The interactions of such species and their metabolic outcome could have direct impacts on infant health, either beneficial (production of short chain fatty acids) or detrimental (accumulation of hydrogen or hydrogen sulfide). We identified mode of delivery as a strong determinant for lactate-producing and -utilizing bacteria levels. These findings present the early establishment of GM with a novel perspective and emphasize the importance of lactate utilization in infancy.

Antibiotic therapy for inpatients with community-acquired pneumonia in a developing country.

PURPOSE: The aim of this study was to identify antibiotic prescription patterns for community-acquired pneumonia (CAP) in Vietnam. METHODS: Medical records for CAP adult patients admitted to 10 hospitals across the country were randomly selected from admission lists during the peak pneumonia season. CAP cases were identified from manual record reviews by clinical pharmacists. Data was collected using a standard data collection tool including patient clinical features on admission, comorbidities, microbiological culture results, and antibiotic regimens. Pneumonia severity was estimated using the CURB-65 score. RESULTS: A total of 649 medical records for adult patients (55.2% male and 52.3% urban residents, median age 68 years) met the selection criteria for CAP. Pneumonia severity was assessed as mild (64.1% of patients), moderate (23.0%), and severe (9.2%). Antibiotics were most frequently administered intravenously (93.4%) and as combination therapy (dual therapy 54.4%, monotherapy 42.5%, and triple therapy 3.1% of patients) regardless of CAP severity. Third-generation cephalosporins were used most frequently (29.3% as monotherapy and 40.4% as combination therapy). Third-generation cephalosporins were most commonly combined with penicillins and/or quinolones. CONCLUSIONS: This first nationwide study provides a baseline profile of antibiotic use in the treatment of CAP. Third-generation cephalosporins were widely used for initial empirical management of CAP, often in combination with quinolones, regardless of CAP severity. The study will assist in providing an evidence base to inform new national antibiotic guidelines for CAP management and will contribute locally relevant data for the national master plan addressing antibiotic resistance and the development of educational interventions to improve CAP management.

Iron supplementation promotes gut microbiota metabolic activity but not colitis markers in human gut microbiota-associated rats.

The global prevalence of Fe deficiency is high and a common corrective strategy is oral Fe supplementation, which may affect the commensal gut microbiota and gastrointestinal health. The aim of the present study was to investigate the impact of different dietary Fe concentrations on the gut microbiota and gut health of rats inoculated with human faecal microbiota. Rats (8 weeks old, n 40) were divided into five (n 8 each) groups and fed diets differing only in Fe concentration during an Fe-depletion period (12 weeks) and an Fe-repletion period (4 weeks) as follows: (1) Fe-sufficient diet throughout the study period; (2) Fe-sufficient diet followed by 70 mg Fe/kg diet; (3) Fe-depleted diet throughout the study period; (4) Fe-depleted diet followed by 35 mg Fe/kg diet; (5) Fe-depleted diet followed by 70 mg Fe/kg diet. Faecal and caecal samples were analysed for gut microbiota composition (quantitative PCR and pyrosequencing) and bacterial metabolites (HPLC), and intestinal tissue samples were investigated histologically. Fe depletion did not significantly alter dominant populations of the gut microbiota and did not induce Fe-deficiency anaemia in the studied rats. Provision of the 35 mg Fe/kg diet after feeding an Fe-deficient diet significantly increased the abundance of dominant bacterial groups such as Bacteroides spp. and Clostridium cluster IV members compared with that of an Fe-deficient diet. Fe supplementation increased gut microbial butyrate concentration 6-fold compared with Fe depletion and did not affect histological colitis scores. The present results suggest that Fe supplementation enhances the concentration of beneficial gut microbiota metabolites and thus may contribute to gut health.

In Vitro Effect of Enzymes and Human Milk Oligosaccharides on FODMAP Digestion and Fecal Microbiota Composition.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) cause intestinal discomfort in patients with irritable bowel syndrome (IBS). An enzyme mix (2500 SU invertase, 2400 GalU α-galactosidase, 10,000 ALU ß-galactosidase) optimized for FODMAP digestion, and/or human milk oligosaccharides (HMO) (2'-FL, DFL, and LNnT), were evaluated for effects on microbial community activity and composition in short-term colonic incubations using the fecal microbiota of four patients with IBS-D symptoms under the following test conditions: (i) FODMAP, (ii) pre-digested (with enzyme mix) FODMAP, (iii) FODMAP + HMO, and (iv) pre-digested FODMAP + HMO. Pre-digested FODMAP reduced short-chain fatty acid (SCFA) production versus FODMAP; HMO restored this. A 10-day experiment with the simulator of the human intestinal microbial ecosystem (SHIME®), using fecal samples from two patients with IBS-D, further evaluated these findings. FODMAP resulted in decreased microbial diversity versus blank. Pre-digestion with the enzyme mix restored microbial diversity, improved FODMAP digestibility, and reduced gas pressure versus undigested FODMAP; however, SCFA production decreased. HMO restored SCFA production along with an increase in gas pressure and increased abundance of Lachnospiraceae. When used in combination, the FODMAP enzyme mix and HMO may resolve FODMAP-related IBS symptoms while maintaining a healthy gut microbiome via prebiotic activity.

Stepwise establishment of functional microbial groups in the infant gut between 6 months and 2 years: A prospective cohort study.

The early intestinal colonization of functional microbial groups plays an essential role in infant gut health, with most studies targeting the initial colonization period from birth to 6 months of age. In a previous report, we demonstrated the metabolic cross-feeding of lactate and identified keystone species specified for lactate utilization in fecal samples of 40 healthy infants. We present here the extension of our longitudinal study for the period from 6 months to 2 years, with a focus on the colonization of functional groups involved in lactate metabolism and butyrate production. We captured the dynamic changes of the gut microbiota and reported a switch in the predominant lactate-producing and lactate-utilizing bacteria, from Veillonella producing propionate in the first year to Anaerobutyrycum hallii producing butyrate in the second year of life. The significant increase in butyrate producers and fecal butyrate concentration was also pinpointed to the weaning period between 6 and 10 months. Correlation analyses further suggested, for the first time, the metabolic cross-feeding of hydrogen in infants. In conclusion, our longitudinal study of 40 Swiss infants provides important insights into the colonization of functional groups involved in lactate metabolism and butyrate production in the first 2 years of life.

Microbial vitamin production mediates dietary effects on diabetic risk.

Adequate levels of essential vitamins are important for the prevention of diabetes. While the main efforts to address this are currently focused on the intake of vitamin supplements, improving and maintaining intrinsic vitamin production capacity, which is determined by gut microbes, has received insufficient attention. In this study, we systematically investigated the relationship between gut microbial vitamin production and factors related to diabetes and cardiometabolic health in a deeply phenotyped cohort, Lifelines-DEEP (N = 1,135). We found that blood glucose-related factors, lipids, circulating inflammation, and fecal short-chain fatty acids are associated with gut microbial vitamin production. Use of laxatives and metformin are associated with increased levels of vitamin B1/B6 biosynthesis pathways. We further reveal a mediatory role for microbial vitamin B1/B2 production on the influence of fruit intake on diabetes risk. This study provides preliminary evidence for microbiome-targeted vitamin metabolism interventions to promote health.

Vitamins, the gut microbiome and gastrointestinal health in humans.

The gut microbiome plays important roles in the maintenance of host health and the pathogenesis of many diseases. Diet is a key modulator of the gut microbiome. There is increasing evidence that nutrients other than fermentable fiber affect the gut microbial composition. In this review, we discuss the effects of vitamins on the gut microbiome, and related gastrointestinal health, based on in vitro, animal and human studies. Some vitamins, when provided in large doses or when delivered to the large intestine, have been shown to beneficially modulate the gut microbiome by increasing the abundance of presumed commensals (vitamins A, B2, D, E, and beta-carotene), increasing or maintaining microbial diversity (vitamins A, B2, B3, C, K) and richness (vitamin D), increasing short chain fatty acid production (vitamin C), or increasing the abundance of short chain fatty acid producers (vitamins B2, E). Others, such as vitamins A and D, modulate the gut immune response or barrier function, thus, indirectly influencing gastrointestinal health or the microbiome. Future research is needed to explore these potential effects and to elucidate the underlying mechanisms and host health benefits.

Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro.

Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.

Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome- a pilot study.

An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.