Impact of fibre supplementation on microbiome and resilience in healthy participants: A randomized, placebo-controlled clinical trial.

BACKGROUND AND AIMS: The gut microbiome exerts important roles in health, e.g., functions in metabolism and immunology. These functions are often exerted via short-chain fatty acid (SCFA) production by gut bacteria. Studies demonstrating causal relationships between interventions targeting the microbiome and clinical outcomes are limited. This study aimed to show a causal relationship between microbiome modulation through fibre intervention and health. METHODS AND RESULTS: This randomized, double-blind, cross-over study included 65 healthy subjects, aged 45-70 years, with increased metabolic risk (i.e., body mass index [BMI] 25-30 kg/m2, low to moderate daily dietary fibre intake, <30g/day). Subjects took daily a fibre mixture of Acacia gum and carrot powder or placebo for 12 weeks, with an 8-week wash-out period. Faecal samples for measurement of SCFAs and microbiome analysis were collected every 4 weeks. Before and after each intervention period subjects underwent the mixed-meal PhenFlex challenge Test (PFT). Health effects were expressed as resilience to the stressors of the PFT and as fasting metabolic and inflammatory state. The fibre mixture exerted microbiome modulation, with an increase in ß-diversity (p < 0.001). α-diversity was lower during fibre mixture intake compared to placebo after 4, 8 and 12 weeks (p = 0.002; p = 0.012; p = 0.031). There was no effect observed on faecal SCFA concentrations, nor on any of the primary clinical outcomes (Inflammatory resilience: p = 0.605, Metabolic resilience: p = 0.485). CONCLUSION: Although the intervention exerted effects on gut microbiome composition, no effects on SCFA production, on resilience or fasting metabolic and inflammatory state were observed in this cohort. REGISTRATION NUMBER CLINICALTRIALS.GOV: NCT04829396.

Local Sources of Protein in Low- and Middle-Income Countries: How to Improve the Protein Quality?

Protein inadequacy is a major contributor to nutritional deficiencies and adverse health outcomes of populations in low- and middle-income countries (LMICs). People in LMICs often consume a diet predominantly based on staple crops, such as cereals or starches, and derive most of their daily protein intakes from these sources. However, plant-based sources of protein often contain low levels of indispensable amino acids (IAAs). Inadequate intake of IAA in comparison with daily requirements is a limiting factor that results in protein deficiency, consequently in the long-term stunting and wasting. In addition, plant-based sources contain factors such as antinutrients that can diminish protein digestion and absorption. This review describes factors that affect protein quality, reviews dietary patterns of populations in LMICs and discusses traditional and novel small- and large-scale techniques that can improve the quality of plant protein sources for enhanced protein bioavailability and digestibility as an approach to tackle malnutrition in LMICs. The more accessible small-scale food-processing techniques that can be implemented at home in LMICs include soaking, cooking, and germination, whereas many large-scale techniques must be implemented on an industrial level such as autoclaving and extrusion. Limitations and considerations to implement those techniques locally in LMICs are discussed. For instance, at-home processing techniques can cause loss of nutrients and contamination, whereas limitations with larger scale techniques include high energy requirements, costs, and safety considerations. This review suggests that combining these small- and large-scale approaches could improve the quality of local sources of proteins, and thereby address adverse health outcomes, particularly in vulnerable population groups such as children, adolescents, elderly, and pregnant and lactating women.

The Polyunsaturated Fatty Acids Eicosapentaenoic Acid and Docosahexaenoic Acid, and Vitamin K1 Modulate the Gut Microbiome: A Study Using an In Vitro Shime Model.

Omega-3 polyunsaturated fatty acids (PUFAs) and vitamins exert multiple beneficial effects on host health, some of which may be mediated through the gut microbiome. We investigated the prebiotic potential of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and lipid-soluble phylloquinone (vitamin K1), each at 0.2x, 1x and 5x using the simulator of the human intestinal microbial ecosystem (SHIME®) to exclude in vivo systemic effects and host-microbe interactions.Microbial community composition and, diversity [shotgun metagenomic sequencing] and microbial activity [pH, gas pressure, and production of short-chain fatty acids (SCFAs)] were measured over a period of 48 h. Fermentations supernatants were used to investigate the effect on gut barrier integrity using a Caco-2/goblet cell co-culture model.We found that EPA, DHA and vitamin K1 increased alpha-diversity at 24 h when compared with control. Moreover, there was an effect on beta-diversity with changes in gut microbial composition, such as an increase in the Firmicutes/Bacteroidetes (F/B) ratio and a consistent increase in Veillonella and Dialister abundances with all treatments. DHA, EPA, and vitamin K1 also modulated metabolic activity of the gut microbiome by increasing total SCFAs which was related mainly to an increase in propionate (highest with EPA and vitamin K1 at 0.2x). Finally, we found that EPA and DHA increased gut barrier integrity with DHA at 1x and EPA at 5x (p < 0.05, respectively). In conclusion, our in vitro data further establish a role of PUFAs and vitamin K to modulate the gut microbiome with effects on the production of SCFAs and barrier integrity.

Development of a workflow for the selection, identification and optimization of lactic acid bacteria with high γ-aminobutyric acid production.

Lactic acid bacteria produce γ-aminobutyric acid (GABA) as an acid stress response. GABA is a neurotransmitter that may improve sleep and resilience to mental stress. This study focused on the selection, identification and optimization of a bacterial strain with high GABA production, for development as a probiotic supplement. The scientific literature and an industry database were searched for probiotics and potential GABA producers. In silico screening was conducted to identify genes involved in GABA production. Subsequently, 17 candidates were screened for in vitro GABA production using thin layer chromatography, which identified three candidate probiotic strains Levilactobacillus brevis DSM 20054, Lactococcus lactis DS75843and Bifidobacterium adolescentis DSM 24849 as producing GABA. Two biosensors capable of detecting GABA were developed: 1. a transcription factor-based biosensor characterized by the interaction with the transcriptional regulator GabR was developed in Corynebacterium glutamicum; and 2. a growth factor-based biosensor was built in Escherichia coli, which used auxotrophic complementation by expressing 4-aminobutyrate transaminase (GABA-T) that transfers the GABA amino group to pyruvate, hereby forming alanine. Consequently, the feasibility of developing a workflow based on co-culture with producer strains and a biosensor was tested. The three GABA producers were identified and the biosensors were encapsulated in nanoliter reactors (NLRs) as alginate beads in defined gut-like conditions. The E. coli growth factor-based biosensor was able to detect changes in GABA concentrations in liquid culture and under gut-like conditions. L. brevis and L. lactis were successfully encapsulated in the NLRs and showed growth under miniaturized intestinal conditions.

Normative cognition and the effects of a probiotic food intervention in first grade children in Côte d'Ivoire.

The cognitive skills critical for success have largely been studied in Western populations, despite the fact that children in low- and middle-income countries are at risk to not reach their full developmental potential. Moreover, scientists should leverage recent discovery to explore means of boosting cognition in at-risk populations. This semi-randomized controlled trial examined normative cognitive development and whether it could be enhanced by consumption of a probiotic food in a sample of 251 4- to 7-year-old children in urban schools in Côte d'Ivoire. Participants completed executive functioning measures at baseline (T1) and 5 months later (T2). After T1, children in one school received a probiotic (N = 74) or placebo (N = 79) fermented dairy food every day they were in school for one semester; children in the other school (N = 98) continued their diet as usual. Children improved on all tests across time (Cohen's d = 0.08-0.30). The effects of probiotic ingestion were inconclusive and are interpreted with caution due to socio-political factors affecting daily administration. Given the general feasibility of the study, we hope that it will serve as an inspiration for future research into child development and sustainable (health-promoting) interventions for school children in developing nations.

Model Selection Reveals the Butyrate-Producing Gut Bacterium Coprococcus eutactus as Predictor for Language Development in 3-Year-Old Rural Ugandan Children.

INTRODUCTION: The metabolic activity of the gut microbiota plays a pivotal role in the gut-brain axis through the effects of bacterial metabolites on brain function and development. In this study we investigated the association of gut microbiota composition with language development of 3-year-old rural Ugandan children. METHODS: We studied the language ability in 139 children of 36 months in our controlled maternal education intervention trial to stimulate children's growth and development. The dataset includes 1170 potential predictors, including anthropometric and cognitive parameters at 24 months, 542 composition parameters of the children's gut microbiota at 24 months and 621 of these parameters at 36 months. We applied a novel computationally efficient version of the all-subsets regression methodology and identified predictors of language ability of 36-months-old children scored according to the Bayley Scales of Infant and Toddler Development (BSID-III). RESULTS: The best three-term model, selected from more than 266 million models, includes the predictors Coprococcus eutactus at 24 months of age, Bifidobacterium at 36 months of age, and language development at 24 months. The top 20 four-term models, selected from more than 77 billion models, consistently include C. eutactus abundance at 24 months, while 14 of these models include the other two predictors as well. Mann-Whitney U tests suggest that the abundance of gut bacteria in language non-impaired children (n = 78) differs from that in language impaired children (n = 61). While anaerobic butyrate-producers, including C. eutactus, Faecalibacterium prausnitzii, Holdemanella biformis, Roseburia hominis are less abundant, facultative anaerobic bacteria, including Granulicatella elegans, Escherichia/Shigella and Campylobacter coli, are more abundant in language impaired children. The overall predominance of oxygen tolerant species in the gut microbiota was slightly higher in the language impaired group than in the non-impaired group (P = 0.09). CONCLUSION: Application of the all-subsets regression methodology to microbiota data established a correlation between the relative abundance of the anaerobic butyrate-producing gut bacterium C. eutactus and language development in Ugandan children. We propose that the gut redox potential and the overall bacterial butyrate-producing capacity in the gut are important factors for language development.

Salivary biomarkers of stress and inflammation in first graders in Côte d'Ivoire: Effects of a probiotic food intervention.

This semi-randomized controlled trial examined the effects of a probiotic food supplement on cortisol and C-reactive protein (CRP) in a sample of 262 four-to seven-year-old children (56% girls) in two economically-disadvantaged schools in an urban setting in Côte d'Ivoire. For one semester, children in one school were randomized to receive a probiotic (N = 79) or placebo (N = 85) fermented dairy food each day they attended school; one child (due to medical reasons) and all children in the other school (N = 98) continued their diets as usual. Children provided two saliva samples at 11:30 on consecutive days at the end of the study. Analyses revealed that the probiotic group had lower cortisol than the placebo or diet-as-usual groups (p = .015); CRP levels were comparable across groups (p = .549). Exploratory analyses suggested that dose and regularity of consumption may impact the biomarkers as well. This study provides the first evidence that a probiotic milk product may lower cortisol in a sample of young, economically-disadvantaged children.

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.

Intravesical bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: a randomised, placebo-controlled, double-blind clinical trial.

BACKGROUND: Urinary tract infections (UTIs) are among the most prevalent microbial diseases and their financial burden on society is substantial. In the context of increasing antibiotic resistance, finding alternative treatments for UTIs is a top priority. We aimed to determine whether intravesical bacteriophage therapy with a commercial bacteriophage cocktail is effective in treating UTI. METHODS: We did a randomised, placebo-controlled, clinical trial, at the Alexander Tsulukidze National Centre of Urology, Tbilisi, Georgia. Men older than 18 years of age, who were scheduled for transurethral resection of the prostate (TURP), with complicated UTI or recurrent uncomplicated UTI but no signs of systemic infection, were allocated by block randomisation in a 1:1:1 ratio to receive intravesical Pyo bacteriophage (Pyophage; 20 mL) or intravesical placebo solution (20 mL) in a double-blind manner twice daily for 7 days, or systemically applied antibiotics (according to sensitivities) as an open-label standard-of-care comparator. Urine culture was taken via urinary catheter at the end of treatment (ie, day 7) or at withdrawal from the trial. The primary outcome was microbiological treatment response after 7 days of treatment, measured by urine culture; secondary outcomes included clinical and safety parameters during the treatment period. Analyses were done in a modified intention-to-treat population of patients having received at least one dose of the allocated treatment regimen. This trial is registered with ClinicalTrials.gov, NCT03140085. FINDINGS: Between June 2, 2017, and Dec 14, 2018, 474 patients were screened for eligibility and 113 (24%) patients were randomly assigned to treatment (37 to Pyophage, 38 to placebo, and 38 to antibiotic treatment). 97 patients (28 Pyophage, 32 placebo, 37 antibiotics) received at least one dose of their allocated treatment and were included in the primary analysis. Treatment success rates did not differ between groups. Normalisation of urine culture was achieved in five (18%) of 28 patients in the Pyophage group compared with nine (28%) of 32 patients in the placebo group (odds ratio [OR] 1·60 [95% CI 0·45-5·71]; p=0·47) and 13 (35%) of 37 patients in the antibiotic group (2·66 [0·79-8·82]; p=0·11). Adverse events occurred in six (21%) of 28 patients in the Pyophage group compared with 13 (41%) of 32 patients in the placebo group (OR 0·36 [95% CI 0·11-1·17]; p=0·089) and 11 (30%) of 37 patients in the antibiotic group (0·66 [0·21-2·07]; p=0·47). INTERPRETATION: Intravesical bacteriophage therapy was non-inferior to standard-of-care antibiotic treatment, but was not superior to placebo bladder irrigation, in terms of efficacy or safety in treating UTIs in patients undergoing TURP. Moreover, the bacteriophage safety profile seems to be favourable. Although bacteriophages are not yet a recognised or approved treatment option for UTIs, this trial provides new insight to optimise the design of further large-scale clinical studies to define the role of bacteriophages in UTI treatment. FUNDING: Swiss Continence Foundation, the Swiss National Science Foundation, and the Swiss Agency for Development and Cooperation. TRANSLATIONS: For the Georgian and German translations of the abstract see Supplementary Materials section.

A Comparative Interrupted Times Series on the Health Impact of Probiotic Yogurt Consumption Among School Children From Three to Six Years Old in Southwest Uganda.

Introduction: Following a school milk feeding program in Southwest Uganda, we initiated a probiotic yogurt school feeding program in the same region in 2018. In order to investigate the potential health benefits from probiotic yogurt we conducted an observational study, where we compared the effect of the consumption of locally produced probiotic yogurt containing Lactobacillus rhamnosus yoba 2012 to milk in pre-primary schoolchildren from different schools on the occurrence of respiratory tract infections (common cold) and skin infections (e.g., tinea capitis). Method: A comparative interrupted time series over a period of 3 weeks of baseline followed by 9 weeks of 100 ml of probiotic yogurt or milk consumption for 5 days per week. In total 584 children attending five different schools were followed during consumption of probiotic yogurt and 532 children attending five other schools during consumption of milk. Incidences of respiratory tract infection symptoms and skin infection symptoms, changes in anthropometric indicators and absenteeism were recorded. Results: Over the course of the study period the incidence rate for common cold symptoms decreased faster in the yogurt group than in the milk group (p = 0.09) resulting in a final RR of 0.85 (95% CI: 0.5-1.4) at the end of the observational period. The incidence rate of skin infection related symptoms also reduced faster in the yogurt group compared to the milk group (p < 0.0001) resulting in a relative risk factor (RR) of 0.6 (CI: 0.4-0.9) at the end of the observational period. Anthropometric indicators and level of absenteeism did not show significant differences between yogurt and milk. Conclusion: Notwithstanding the observed positive trend and effect of probiotic yogurt on the incidences of common cold and skin infections, respectively, we consider the results of this comparative interrupted time series inconclusive due to differences in the recorded health parameters between the probiotic yogurt and milk control groups at base line, and fluctuations over the course of the intervention period. An improved study design, with more uniform study groups, a longer intervention period and a third control group without yogurt or milk is required to draw definitive conclusions.

Aflatoxins: Occurrence, Exposure, and Binding to Lactobacillus Species from the Gut Microbiota of Rural Ugandan Children.

Chronic exposure of children in sub-Saharan Africa to aflatoxins has been associated with low birth weight, stunted growth, immune suppression, and liver function damage. Lactobacillus species have been shown to reduce aflatoxin contamination during the process of food fermentation. Twenty-three Lactobacillus strains were isolated from fecal samples obtained from a cohort of rural Ugandan children at the age of 54 to 60 months, typed by 16S rRNA gene sequencing, and characterized in terms of their ability to bind aflatoxin B1 in vitro. Evidence for chronic exposure of these children to aflatoxin B1 in the study area was obtained by analysis of local foods (maize flour and peanuts), followed by the identification of the breakdown product aflatoxin M1 in their urine samples. Surprisingly, Lactobacillus in the gut microbiota of 140 children from the same cohort at 24 and 36 months showed the highest positive correlation coefficient with stunting among all bacterial genera identified in the stool samples. This correlation was interpreted to be associated with dietary changes from breastfeeding to plant-based solid foods that pose an additional risk for aflatoxin contamination, on one hand, and lead to increased intake of Lactobacillus species on the other.

Vitamins for the Gut Microbiome.

A main target in microbiome research is the understanding and ability to safely and effectively modulate the microbiome to improve health. Hereto, we discuss the role of vitamins in relation to the gut microbiome and present a rationale for the modulation of gut microbial communities via selected systemic and colon-targeted vitamin administration.

Probiotic Enrichment and Reduction of Aflatoxins in a Traditional African Maize-Based Fermented Food.

Fermentation of food products can be used for the delivery of probiotic bacteria and means of food detoxification, provided that probiotics are able to grow, and toxins are reduced in raw materials with minimal effects on consumer acceptability. This study evaluated probiotic enrichment and detoxification of kwete, a commonly consumed traditional fermented cereal beverage in Uganda, by the use of starter culture with the probiotic Lactobacillus rhamnosus yoba 2012 and Streptococcus thermophilus C106. Probiotic kwete was produced by fermenting a suspension of ground maize grain at 30 °C for a period of 24 h, leading to a decrease of the pH value to ≤ 4.0 and increase in titratable acidity of at least 0.2% (w/v). Probiotic kwete was acceptable to the consumers with a score of ≥6 on a 9-point hedonic scale. The products were stable over a month's study period with a mean pH of 3.9, titratable acidity of 0.6% (w/v), and Lactobacillus rhamnosus counts >108 cfu g-1. HPLC analysis of aflatoxins of the water-soluble fraction of kwete indicated that fermentation led to an over 1000-fold reduction of aflatoxins B1, B2, G1, and G2 spiked in the raw ingredients. In vitro fluorescence spectroscopy confirmed binding of aflatoxin B1 to Lactobacillus rhamnosus with an efficiency of 83.5%. This study shows that fermentation is a means to enrich with probiotics and reduce widely occurring aflatoxin contamination of maize products that are consumed as staple foods in sub-Saharan Africa.

Naturally Fermented Milk From Northern Senegal: Bacterial Community Composition and Probiotic Enrichment With Lactobacillus rhamnosus.

A variety of foods fermented with lactic acid bacteria serve as dietary staples in many African communities; yet, their bacterial profiles are poorly characterized. The integration of health-promoting probiotics into naturally fermented milk products could make a profound impact on human health. Here, we characterize the bacterial community composition of a naturally fermented milk product (lait caillé) from northern Senegal, prepared in wooden bowls (lahals) with a bacterial biofilm to steer the fermentation process. We incorporated a probiotic starter culture containing the most documented probiotic strain Lactobacillus rhamnosus GG (generic strain name yoba 2012) into the local fermentation process. Bar-coded 16S rRNA amplicon sequencing of lait caillé samples indicated that the bacterial community of lait caillé has high species richness with over 100 bacterial genera; however, few have high abundance. In contrast to the diverse bacterial compositions of other characterized naturally fermented milk products, the composition of lait caillé predominantly consists of the lactic acid bacteria Streptococcus and Lactobacillus, resembling the bacterial composition in regular yogurt. The bacterial community composition of lait caillé varies geographically based on the presence of some genera, including Lactoccoccus, Enterococcus, Bifidobacterium, and Bacillus, but this trend is not consistent within production communities. The diversity of bacterial communities is much higher in the lahal biofilm than in the naturally fermented milk products, which is in turn greater than in commercial yogurts. Addition of a starter culture with L. rhamnosus yoba 2012 to milk in lahals led to substantial growth of this probiotic bacterium during the fermentation process. Two independent quantitative PCR-analyses specific for L. rhamnosus yoba 2012 indicated a 20- to 60-fold increase in the total number of probiotic bacteria in the first batch after inoculation. A similar increase of the probiotic was observed in a variation of lait caillé prepared with carbohydrate-rich millet granules (thiakry) added prior to fermentation. This study shows the feasibility of integrating health-promoting probiotic strains into naturally fermented foods produced in regions with a high prevalence of malnutrition.

The Probiotic Lactobacillus rhamnosus for Alleviation of Helicobacter pylori-Associated Gastric Pathology in East Africa.

The probiotic Lactobacillus rhamnosus GG (LGG) can play a role in establishing a harmless relationship with Helicobacter pylori and reduce gastric pathology in East African populations. H. pylori has the ability to inhabit the surface of the mucous layer of the human stomach and duodenum. In the developing world, an estimated 51% of the population is carrier of H. pylori, while in some Western countries these numbers dropped below 20%, which is probably associated with improved sanitation and smaller family sizes. Colonization by H. pylori can be followed by inflammation of the gastric mucus layer, and is a risk factor in the development of atrophic gastritis, peptic ulcers and gastric cancer. Notwithstanding the higher prevalence of H. pylori carriers in developing countries, no equal overall increase in gastric pathology is found. This has been attributed to a less pro-inflammatory immune response to H. pylori in African compared to Caucasian populations. In addition, a relatively low exposure to other risk factors in certain African populations may play a role, including the use of non-steroidal anti-inflammatory drugs, smoking, and diets without certain protective factors. A novel approach to the reduction of H. pylori associated gastric pathology is found in the administration of the probiotic bacterium Lactobacillus rhamnosus yoba 2012 (LRY), the generic variant of LGG. This gastro-intestinal isolate inhibits H. pylori by competition for substrate and binding sites as well as production of antimicrobial compounds such as lactic acid. In addition, it attenuates the host's H. pylori-induced apoptosis and inflammation responses and stimulates angiogenesis in the gastric and duodenal epithelium. The probiotic LRY is not able to eradicate H. pylori completely, but its co-supplementation in antibiotic eradication therapy has been shown to relieve side effects of this therapy. In Uganda, unlike other African countries, gastric pathology is relatively common, presumably resulting from the lack of dietary protective factors in the traditional diet. Supplementation with LRY through local production of probiotic yogurt, could be a solution to establish a harmless relationship with H. pylori and reduce gastric pathology and subsequent eradication therapy treatment.

Adapted Bacteriophages for Treating Urinary Tract Infections.

Urinary tract infections (UTIs) are among the most widespread microbial diseases and their economic impact on the society is substantial. The continuing increase of antibiotic resistance worldwide is worrying. As a consequence, well-tolerated, highly effective therapeutic alternatives are without delay needed. Although it has been demonstrated that bacteriophage therapy may be effective and safe for treating UTIs, the number of studied patients is low and there is a lack of randomized controlled trials (RCTs). The present study has been designed as a two-phase prospective investigation: (1) bacteriophage adaptation, (2) treatment with the commercially available but adapted Pyo bacteriophage. The aim was to evaluate feasibility, tolerability, safety, and clinical/microbiological outcomes in a case series as a pilot for a double-blind RCT. In the first phase, patients planned for transurethral resection of the prostate were screened (n = 130) for UTIs and enrolled (n = 118) in the study when the titer of predefined uropathogens (Staphylococcus aureus, E. coli, Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis) in the urine culture was ≥104 colony forming units/mL. In vitro analysis showed a sensitivity for uropathogenic bacteria to Pyo bacteriophage of 41% (48/118) and adaptation cycles of Pyo bacteriophage enhanced its sensitivity to 75% (88/118). In the second phase, nine patients were treated with adapted Pyo bacteriophage and bacteria titer decreased (between 1 and 5 log) in six of the nine patients (67%). No bacteriophage-associated adverse events have been detected. The findings of our prospective two-phase study suggest that adapted bacteriophage therapy might be effective and safe for treating UTIs. Thus, well-designed RCTs are highly warranted to further define the role of this potentially revolutionizing treatment option.

Feasibility of A Novel On-Site Detection Method for Aflatoxin in Maize Flour from Markets and Selected Households in Kampala, Uganda.

In sub-Saharan Africa, there is a high demand for affordable and accessible methods for on-site detection of aflatoxins for appropriate food safety management. In this study, we validated an electrochemical immunosensor device by the on-site detection of 60 maize flour samples from six markets and 72 samples from households in Kampala. The immunosensor was successfully validated with a linear range from 0.7 ± 0.1 to 11 ± 0.3 µg/kg and limit of detection (LOD) of 0.7 µg/kg. The maize flour samples from the markets had a mean total aflatoxin concentration of 7.6 ± 2.3 µg/kg with approximately 20% of the samples higher than 10 µg/kg, which is the maximum acceptable level in East Africa. Further down the distribution chain, at the household level, approximately 45% of the total number contained total aflatoxin levels higher than the acceptable limit. The on-site detection method correlated well with the established laboratory-based HPLC and ELISA-detection methods for aflatoxin B1 with the correlation coefficients of 0.94 and 0.98, respectively. This study shows the feasibility of a novel on-site detection method and articulates the severity of aflatoxin contamination in Uganda.

Lactobacillus rhamnosus Probiotic Food as a Tool for Empowerment Across the Value Chain in Africa.

Perhaps by serendipity, but Lactobacillus rhamnosus has emerged from the 1980s as the most researched probiotic species. The many attributes of the two main probiotic strains of the species, L. rhamnosus GG and GR-1, have made them suitable for applications to developing countries in Africa and beyond. Their use with a Streptococcus thermophilus starter strain C106, in the fermentation of milk, millet, and juices has provided a means to reach over 250,000 consumers of the first probiotic food on the continent. The social and economical implications for this translational research are significant, and especially pertinent for people living in poverty, with malnutrition and exposure to environmental toxins and infectious diseases including HIV and malaria. This example of probiotic applications illustrates the power of microbes in positively impacting the lives of women, men, and children, right across the food value chain.

Silk Route to the Acceptance and Re-Implementation of Bacteriophage Therapy-Part II.

This perspective paper follows up on earlier communications on bacteriophage therapy that we wrote as a multidisciplinary and intercontinental expert-panel when we first met at a bacteriophage conference hosted by the Eliava Institute in Tbilisi, Georgia in 2015. In the context of a society that is confronted with an ever-increasing number of antibiotic-resistant bacteria, we build on the previously made recommendations and specifically address how the Nagoya Protocol might impact the further development of bacteriophage therapy. By reviewing a number of recently conducted case studies with bacteriophages involving patients with bacterial infections that could no longer be successfully treated by regular antibiotic therapy, we again stress the urgency and significance of the development of international guidelines and frameworks that might facilitate the legal and effective application of bacteriophage therapy by physicians and the receiving patients. Additionally, we list and comment on several recently started and ongoing clinical studies, including highly desired double-blind placebo-controlled randomized clinical trials. We conclude with an outlook on how recently developed DNA editing technologies are expected to further control and enhance the efficient application of bacteriophages.