Soluble Non-Starch Polysaccharides From Plantain (Musa x paradisiaca L.) Diminish Epithelial Impact of Clostridioides difficile

Clostridioides difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea. Adhesion of this Gram-positive pathogen to the intestinal epithelium is a crucial step in CDI, with recurrence and relapse of disease dependent on epithelial interaction of its endospores. Close proximity, or adhesion of, hypervirulent strains to the intestinal mucosa are also likely to be necessary for the release of C. difficile toxins, which when internalized, result in intestinal epithelial cell rounding, damage, inflammation, loss of barrier function and diarrhoea. Interrupting these C. difficile-epithelium interactions could therefore represent a promising therapeutic strategy to prevent and treat CDI. Intake of dietary fibre is widely recognised as being beneficial for intestinal health, and we have previously shown that soluble non-starch polysaccharides (NSP) from plantain banana (Musa spp.), can block epithelial adhesion and invasion of a number of gut pathogens, such as E. coli and Salmonellae. Here, we assessed the action of plantain NSP, and a range of alternative soluble plant fibres, for inhibitory action on epithelial interactions of C. difficile clinical isolates, purified endospore preparations and toxins. We found that plantain NSP possessed ability to disrupt epithelial adhesion of C. difficile vegetative cells and spores, with inhibitory activity against C. difficile found within the acidic (pectin-rich) polysaccharide component, through interaction with the intestinal epithelium. Similar activity was found with NSP purified from broccoli and leek, although seen to be less potent than NSP from plantain. Whilst plantain NSP could not block the interaction and intracellular action of purified C. difficile toxins, it significantly diminished the epithelial impact of C. difficile, reducing both bacteria and toxin induced inflammation, activation of caspase 3/7 and cytotoxicity in human intestinal cell-line and murine intestinal organoid cultures. Dietary supplementation with soluble NSP from plantain may therefore confer a protective effect in CDI patients by preventing adhesion of C. difficile to the mucosa, i.e. a “contrabiotic” effect, and diminishing its epithelial impact. This suggests that plantain soluble dietary fibre may be a therapeutically effective nutritional product for use in the prevention or treatment of CDI and antibiotic-associated diarrhoea.

Role of probiotics and vitamins in maintaining a healthy gut microbiome: recent advances

While the concept of probiotics is not new, science based approaches to developing targeted probiotic products are a renewed interest. Probiotics and the microbiome is now being considered as having a blueprint of good health, unique to every human. Along with the well-known and established health benefits like reduced antibiotic associated diarrhoea and colic symptoms, eczema, necrotising enterocolitis, acute paediatric infections like diahorrea and upper respiratory tract infections; probiotics are now considered as beneficial for maintaining mental well-being as well. This new branch of disease management is now termed as Nutritional neuroscience and these beneficial gut bacteria are referred to as psychobiotics. It is important to identify the specific strains of probiotics and characterize them and conduct randomised controlled trials to establish these benefits. With emerging data related to role of vitamins in modulating the gut microbiome, combining pre and probiotics with micronutrients is likely to result in powerful functional foods boosting host immunity.

Probiotics for the prevention of antibiotic-associated diarrhoea: a systematic review and meta-analysis

ObjectiveTo evaluate existing evidence for the use of probiotics in preventing antibiotic-associated diarrhoea (AAD) in adults.DesignSystematic review and meta-analysis of randomised controlled trials (RCTs).Data sourcesWe performed a literature search of the electronic databases CINAHL Plus, EMBASE, MEDLINE (Ovid) and Web of Science from database inception to May 2021 as well as hand searching of trial registries and reference lists of related reviews.Study selectionTwo reviewers identified whether RCTs met the following inclusion criteria: adult population to whom antibiotics were administered; a probiotic intervention; a placebo, alternative dose, alternative probiotic strain or no treatment control; and incidence of AAD as the outcome.Data extraction and synthesisTwo reviewers independently collected data and assessed risk of bias using preconstructed data extraction forms. We used a random effects model for all analyses. Subgroup analyses were performed to evaluate species-specific and dose-specific response.ResultsForty-two studies (11,305 participants) were included in this review. The pooled analysis suggests that co-administration of probiotics with antibiotics reduces the risk of AAD in adults by 37% (risk ratio (RR)=0.63 (95% CI 0.54 to 0.73), p<0.00001). The overall quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria was found to be moderate. In subgroup analyses, high dose compared with low dose of the same probiotic demonstrated a positive protective effect (RR 0.54 (95% CI 0.38 to 0.76), p<0.01), and only certain species, mainly of the lactobacillus and bifidobacteria genera, were found to be effective. Studies with a low baseline AAD risk did not show any difference in risk but studies with moderate or high baseline AAD risk demonstrated a significant risk reduction.ConclusionsProbiotics are effective for preventing AAD. Secondary analyses of higher dosages and certain species have shown increased effectiveness. Our results may not be applicable in clinical scenarios of lower baseline AAD risk.

PREVALENCE OF CLOSTRIDIUM DIFFICILE INFECTION IN PATIENTS EXPOSED TO ANTIBIOTICS IN PREVIOUS 6 WEEKS AND ADMITTED WITH DIARRHEA IN A TERTIARY CARE HOSPITAL.

Clostridium difficile is a signicant cause of morbidity and mortality among hospitalized patients, and the incidence of C. difficile infection (CDI) has dramatically increased due to frequent usage of broadspectrum antibiotics in these patients. The wide variation in the spectrum of clinical manifestations of CDI makes the diagnosis difcult. Further, the wide range of variability in the sensitivity and specicity of the various diagnostic methods and the high cost of these methods add to the difculty. It is a spore-forming gram-positive anaerobic organism. Until the 1970s, it was considered as a microorganism that is rarely present in normal intestinal microbiota. But it was not until 1978 that C. difcile was identied as a cause of [1] pseudomembranous colitis . Since then, C. difcile has been recognized as a common cause of antibiotic associated diarrhoea and nosocomial diarrhoea. The incidence of C. difcile infection (CDI) varies from place to place. In India, it is known to infect up to 25 % of [2] people taking antibiotics

Probiotics to reduce antibiotic administration in care home residents aged 65 years and older: the PRINCESS RCT

Background Care homes are an increasingly important sector of care. Care home residents are particularly vulnerable to infections and are often prescribed antibiotics, driving antibiotic resistance. Probiotics may be a cheap and safe way to reduce antibiotic use. Efficacy and possible mechanisms of action are yet to be rigorously evaluated in this group. Objective The objective was to evaluate efficacy and explore mechanisms of action of a daily oral probiotic combination in reducing antibiotic use and infections in care home residents. Design This was a multicentre, parallel, individually randomised, placebo-controlled, double-blind trial, with qualitative evaluation and mechanistic studies. Setting A total of 310 care home residents were randomised from 23 UK care homes (from December 2016 to May 2018). Participants The participants were care home residents aged ≥ 65 years who were willing and able to give informed consent or, if they lacked capacity to consent, had a consultee to advise about participation on their behalf. Intervention A daily capsule containing an oral probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 (n = 155) or matched placebo (n = 155) for up to 1 year. Main outcome measures The primary outcome was cumulative systemic antibiotic administration days for all-cause infections. Secondary outcomes included incidence and duration of infections, antibiotic-associated diarrhoea, quality of life, hospitalisations and the detection of resistant Enterobacterales cultured from stool samples (not exclusively). Methods Participants were randomised (1 : 1) to receive capsules containing probiotic or matched placebo. Minimisation was implemented for recruiting care home and care home resident sex. Care home residents were followed up for 12 months with a review by a research nurse at 3 months and at 6–12 months post randomisation. Care home residents, consultees, care home staff and all members of the trial team, including assessors and statisticians, were blinded to group allocation. Results Care home residents who were randomised to probiotic had a mean 12.9 cumulative systemic antibiotic administration days (standard error 1.49 days) (n = 152) and care home residents randomised to placebo had a mean 12.0 cumulative systemic antibiotic administration days (standard error 1.50 days) (n = 153) (adjusted incidence rate ratio = 1.13, 95% confidence interval 0.79 to 1.63; p = 0.495). There was no evidence of any beneficial effects on incidence and duration of infections, antibiotic-associated diarrhoea, quality of life, hospitalisations, the detection of resistant Enterobacterales cultured from stool samples or other secondary outcomes. There was no evidence that this probiotic combination improved blood immune cell numbers, subtypes or responses to seasonal influenza vaccination. Conclusions Care home residents did not benefit from daily consumption of a combination of the probiotics Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 to reduce antibiotic consumption. Limitations Limitations included the following: truncated follow-up of some participants; higher than expected probiotics in stool samples at baseline; fewer events than expected meant that study power may have been lower than anticipated; standard infection-related definitions were not used; and findings are not necessarily generalisable because effects may be strain specific and could vary according to patient population. Future work Future work could involve further rigorous efficacy, mechanisms and effectiveness trials of other probiotics in other population groups and settings regarding antibiotic use and susceptibility to and recovery from infections, in which potential harms should be carefully studied. Trial registration Current Controlled Trials ISRCTN16392920. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 7. See the NIHR Journals Library website for further project information.

Antibiotic associated diarrhoea in paediatric outpatient practice

Background: To document the profile of antibiotic associated diarrhoea (AAD) in children aged 6 months to 15 years receiving oral antibiotics.Methods: Prospective study of children attending the out-patient department, who were started on oral antibiotic for indications other than gastrointestinal infections. Data collection was done with a questionnaire and follow up was done by telephone.Results: Of the 1022 children, seven developed AAD (0.68%). Twenty-nine other children had loose stools but did not fulfil the criteria of AAD. Of 436 children who received Amoxicillin clavulanate, 4 developed AAD. One each from 361 on amoxicillin, 9 on ciprofloxacin and 8 on erythromycin developed AAD. Five of the seven children who had diarrhoea were less than two years (71.4%).Conclusions: Incidence of AAD is very low in an out-patient setting. In all cases, diarrhoea subsided on stopping the antibiotic. Children below two years of age and those on Amoxicillin clavulanate have a significantly higher risk.

Clinical evaluation of the synbiotic Prodefen Plus® in the prevention of the antibiotic-associated diarrhoea in subjects requiring antibiotic treatment

Prodefen® is a dietary food supplement formulated as a synbiotic that has shown additional benefit to the standard supportive therapy in the management of acute viral diarrhoea in children. There is scarce evidence of this synbiotic in adults. The objective of this randomised double blind placebo-controlled clinical trial was to evaluate the efficacy and safety of Prodefen Plus® in the prevention of antibiotic-associated diarrhoea (AAD) in an adult population requiring either antibiotic treatment for an oral infection or antibiotic prophylaxis for a dental surgical procedure in a dental consultation. 151 subjects were randomised to the active (synbiotic) or control arm (placebo) for 14 days. There was a significantly higher reduction in the AAD incidence, and an improvement in the stool consistency in the active group. A higher reduction in both the frequency and duration of the diarrhoea episodes in the active group was also observed, as it was an improved perception of the diarrhoea severity. Overall, the study medication was well tolerated. In conclusion, results from this study confirm the beneficial effect of the synbiotic administered as adjuvant therapy in preventing the antibiotic-associated diarrhoea.