Use of probiotics to correct dysbiosis of normal microbiota following disease or disruptive events: a systematic review.
ABSTRACT: To assess the evidence for the claim probiotics can correct dysbiosis of the normal microbiota resulting from disease or disruptive events.Systematic review of published clinical trials of patients receiving a probiotic intervention for the prevention or treatment of various diseases.Sources searched (1985-2013): PubMed, EMBASE, Cochrane Database of Systematic Reviews, CINAHL, AMED and ISI Web of Science. Three on-line clinical trial registries were searched: Cochrane Central Register of Controlled trials, MetaRegister of Controlled Trials and National Institutes of Health.Included studies were randomised clinical trials of probiotic interventions having microbiological assays. Studies were evaluated following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for specific probiotic strains. A standard data extraction form was used to collect the raw data.The primary outcome is the degree of microbiota correction by specific probiotic strains. Secondary outcome was the association between the degree of dysbiosis correction and clinical efficacy.The review of the literature found three distinct study designs: model A (restoration) assayed patients enrolled with a healthy, undisturbed microbiota and then assayed postdisruptive event and probiotic therapy; model B (alteration) assayed patients with pre-existing disrupted microbiota and then postprobiotic therapy; model C (no dysbiosis) assayed volunteers with no disruptive event prebiotic and postprobiotic. From a total of 63 trials, 83% of the probiotic products using model A restored the microbiota, 56% using model B improved the microbiota and only 21% using model C had any effect on microbiota. Clinical efficacy was more commonly associated with strains capable of restoration of the normal microbiota.The ability to assess the degree of dysbiosis improvement is dependent on the enrolled population and the timing of microbiological assays. The functional claim for correcting dysbiosis is poorly supported for most probiotic strains and requires further research.PROSPERO (CRD42014007224).
Project description:Inflammation is a major risk factor of morbidity and mortality in older adults. Although its precise etiology is unknown, low-grade inflammation in older adults is commonly associated with increased intestinal epithelial permeability (leaky gut) and abnormal (dysbiotic) gut microbiota. The increasing older population and lack of treatments to reduce aging-related microbiota dysbiosis, leaky gut, and inflammation culminates in a rise in aging-related comorbidities, constituting a significant public health concern. Here, we demonstrate that a human-origin probiotic cocktail containing 5 Lactobacillus and 5 Enterococcus strains isolated from healthy infant gut prevented high-fat diet-induced (HFD-induced) microbiota dysbiosis, leaky gut, inflammation, metabolic dysfunctions, and physical function decline in older mice. Probiotic-modulated gut microbiota primarily reduced leaky gut by increasing tight junctions, which in turn reduced inflammation. Mechanistically, probiotics modulated microbiota in a way to increase bile salt hydrolase activity, which in turn increased taurine abundance in the gut that stimulated tight junctions and suppressed gut leakiness. Furthermore, in Caenorhabditis elegans, taurine increased life span, reduced adiposity and leaky gut, and enhanced physical function. The results suggest that such probiotic therapies could prevent or treat aging-related leaky gut and inflammation in the elderly.
Project description:Human microbiota seems to play a key role in endocrine and reproductive systems. Fortunately, microbiota reproductive dysbiosis start to be treated by probiotics using typical species from genus Lactobacillus. This work presents the compiled and analysed results from the most up-to-date information from clinical trials regarding microbiota, fertility, probiotics and oral route administration, reviewing open access scientific documents. These studies analyse the clinical impact of probiotics administered on several endocrine disorders' manifestations in women: mastitis; vaginal dysbiosis; pregnancy complication disorders; and polycystic ovary syndrome. In all cases, the clinical modulation achieved by probiotics was evaluated positively through the improvement of specific disease outcomes with the exception of the pregnancy disorders studies, where the sample sizes results were statistically insufficient. High amounts of studies were discarded because no data were provided on specific probiotic strains, doses, impact on the individual autochthon microbiota, or data regarding specific hormonal values modifications and endocrine regulation effects. However, most of the selected studies with probiotics contained no protocolised administration. Therefore, we consider that intervention studies with probiotics might allocate the focus, not only in obtaining a final outcome, but in how to personalise the administration according to the disorder to be palliated.
Project description:In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia's gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus.
Project description:BACKGROUND:A wide debate is ongoing regarding the role of cutaneous dysbiosis in the pathogenesis and evolution of difficult-to-treat chronic wounds. Nowadays, probiotic treatment considered as an useful tool to counteract dysbiosis but the evidence in regard to their therapeutic use in the setting of difficult-to-treat cutaneous ulcers is still poor. AIM:CLINICAL REPORT: An 83-year-old woman suffering a critical limb ischemia and an infected difficult-to-treat ulcerated cutaneous lesion of the right leg, was complementary treated with local application of a mixture of probiotic bacteria. METHODS:Microbiological and metabolomic analysis were conducted on wound swabs obtained before and after bacteriotherapy. RESULTS:During the treatment course, a progressive healing of the lesion was observed with microbiological resolution of the polymicrobial infection of the wound. Metabolomic analysis showed a significant difference in the local concentration of propionate, 2-hydroxyisovalerate, 2-oxoisocaproate, 2,3-butanediol, putrescine, thymine, and trimethylamine before and after bacteriotherapy. CONCLUSION:The microbiological and metabolomic results seem to confirm the usefulness of complementary probiotic treatment in difficult-to-treat infected wounds. Further investigations are needed to confirm these preliminary findings.
Project description:The introduction of a strain or consortium has often been considered as a potential solution to restore microbial ecosystems. Extensive research on the skin microbiota has led to the development of probiotic products (with live bacterial strains) that are likely to treat dysbiosis. However, the effects of such introductions on the indigenous microbiota have not yet been investigated. Here, through a daily application of Lactobacillus reuteri DSM 17938 on volunteers' forearm skin, we studied in vivo the impact of a probiotic on the indigenous skin bacterial community diversity using Terminal-Restriction Fragment Length Polymorphism (T-RFLP) for 3 weeks. The results demonstrate that Lactobacillus reuteri DSM 17938 inoculum had a transient effect on the indigenous community, as the resilience phenomenon was observed within the skin microbiota. Moreover, Lactobacillus reuteri DSM 17938 monitoring showed that, despite a high level of detection after 2 weeks of application, thereafter the colonization rate drops drastically. The probiotic colonization rate was correlated significantly to the effect on the indigenous microbial community structure. These preliminary results suggest that the success of probiotic use and the potential health benefits resides in the interactions with the human microbiota.
Project description:Aim:Probiotic bacteria administered directly after birth to preterm neonates may improve gastrointestinal function and may reduce the incidence of late-onset sepsis, which is a frequent complication in this group. Purpose:The main objective of this study was to evaluate whether a new probiotic bacterial mixture of Lactobacillus rhamnosus KL53A and Bifidobacterium breve PB04 given to preterm, low-birth-weight neonates would influence composition of their gut microbiota and sepsis rates. Patients and methods:This study was a multicenter, randomized, double-blind, placebo-controlled trial conducted in clinical centers of neonatal care in Poland. A probiotic or placebo preparation was given twice daily to 181 preterm low-birth-weight neonates who were eligible for enteral feeding between July 2012 and July 2013. The probiotic was given to 90 neonates, while placebo was given to 91 neonates. The gut microbiota was monitored by microbiological analysis of stool samples. Sepsis episodes were detected on the basis of clinical and laboratory findings and confirmed by blood cultures. Results:Tested probiotic administration resulted in continuous increase of the Lactobacillus and Bifidobacterium counts in the gut microbiota. The applied tested strains successfully colonized the neonates gut since they were present in over 90% of stool samples, which was confirmed by molecular analysis. Regardless of the study group (probiotic or placebo), B. breve colonization correlated with lower staphylococcal sepsis incidence, which was irrespective of whether probiotics were given. No sepsis case caused by strains included in study probiotic was recorded. Conclusion:Appropriately selected and characterized probiotic bacteria may be safely given to preterm neonates to normalize their distorted gut microbiota and may contribute to lower staphylococcal sepsis rates.
Project description:Obesity is a growing health threat worldwide. Administration of probiotics in obesity has also parallelly increased but without any protocolization. We conducted a systematic review exploring the administration pattern of probiotic strains and effective doses for obesity-related disorders according to their capacity of positively modulating key biomarkers and microbiota dysbiosis. Manuscripts targeting probiotic strains and doses administered for obesity-related disorders in clinical studies were sought. MEDLINE, Scopus, Web of Science, and Cochrane Library databases were searched using keywords during the last fifteen years up to April 2020. Two independent reviewers screened titles, abstracts, and then full-text papers against inclusion criteria according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. From 549 interventional reports identified, we filtered 171 eligible studies, from which 24 full-text assays were used for calculating intervention total doses (ITD) of specific species and strains administered. Nine of these reports were excluded in the second-step because no specific data on gut microbiota modulation was found. Six clinical trials (CT) and 9 animal clinical studies were retained for analysis of complete outcome prioritized (body mass index (BMI), adiposity parameters, glucose, and plasma lipid biomarkers, and gut hormones). Lactobacillus spp. administered were double compared to Bifidobacterium spp.; Lactobacillus as single or multispecies formulations whereas most Bifidobacteria only through multispecies supplementations. Differential factors were estimated from obese populations' vs. obesity-induced animals: ITD ratio of 2 × 106 CFU and patterns of administrations of 11.3 weeks to 5.5 weeks, respectively. Estimation of overall probiotics impact from selected CT was performed through a random-effects model to pool effect sizes. Comparisons showed a positive association between the probiotics group vs. placebo on the reduction of BMI, total cholesterol, leptin, and adiponectin. Moreover, negative estimation appeared for glucose (FPG) and CRP. While clinical trials including data for positive modulatory microbiota capacities suggested that high doses of common single and multispecies of Lactobacillus and Bifidobacterium ameliorated key obesity-related parameters, the major limitation was the high variability between studies and lack of standardized protocols. Efforts in solving this problem and searching for next-generation probiotics for obesity-related diseases would highly improve the rational use of probiotics.
Project description:Recent advances in culture-free microbiological techniques bring new understanding of the role of intestinal microbiota in heath and performance. Intestinal microbial communities in chickens assume a near-stable state within the week which leaves a very small window for permanent microbiota remodelling. It is the first colonisers that determine the fate of microbial community in humans and birds alike, and after the microbiota has matured there are very small odds for permanent modification as stable community resists change. In this study we inoculated broiler chicks immediately post hatch, with 3 species of Lactobacillus, identified by sequencing of 16S rRNA and pheS genes as L. ingluviei, L. agilis and L. reuteri. The strains were isolated from the gut of healthy chickens as reproducibly persistent Lactobacillus strains among multiple flocks. Birds inoculated with the probiotic mix reached significantly higher weight by 28 days of age. Although each strain was able to colonise when administered alone, administering the probiotic mix at-hatch resulted in colonisation by only L. ingluviei. High initial abundance of L. ingluviei was slowly reducing, however, the effects of at-hatch administration of the Lactobacillus mix on modifying microbiota development and structure remained persistent. There was a tendency of promotion of beneficial and reduction in pathogenic taxa in the probiotic administered group.
Project description:BACKGROUND:Postnatal growth restriction (PNGR) in premature infants increases risk of pulmonary hypertension (PH). In a rodent model, PNGR causes PH, while combining PNGR and hyperoxia increases PH severity. We hypothesized that PNGR causes intestinal dysbiosis and that treatment with a probiotic attenuates PNGR-associated PH. METHOD:Pups were randomized at birth to room air or 75% oxygen (hyperoxia), to normal milk intake (10 pups/dam) or PNGR (17 pups/dam), and to probiotic Lactobacillus reuteri DSM 17938 or phosphate-buffered saline. After 14 days, PH was assessed by echocardiography and right ventricular hypertrophy (RVH) was assessed by Fulton's index (right ventricular weight/left ventricle?+?septal weight). The small bowel and cecum were analyzed by high-throughput 16S ribosomal RNA gene sequencing. RESULTS:PNGR with or without hyperoxia (but not hyperoxia alone) altered the microbiota of the distal small bowel and cecum. Treatment with DSM 17938 attenuated PH and RVH in pups with PNGR, but not hyperoxia alone. DSM 17938 treatment decreased ?-diversity. The intestinal microbiota differed based on oxygen exposure, litter size, and probiotic treatment. CONCLUSION:PNGR causes intestinal dysbiosis and PH. Treatment with DSM 17938 prevents PNGR-associated RVH and PH. Changes in the developing intestine and intestinal microbiota impact the developing lung vasculature and RV.
Project description:The present study was undertaken to produce probiotic Caciotta cheeses from pasteurized ewes' milk by using different combinations of autochthonous microbial cultures, containing putative probiotic strains, and evaluate their influence on gross composition, lipid components, sensory properties and microbiological and metabolite profiles of the cheeses throughout ripening process. A control cheese was produced using commercial starter cultures. The hydrophilic molecular pools (mainly composed by amino acids, organic acids, and carbohydrates) were characterized by means of 1H NMR spectroscopy, while the cholesterol, ?-tocopherol and fatty acid composition by HPLC-DAD/ELSD techniques. Conventional culturing and a PCR-DGGE approach using total cheese DNA extracts were used to analyze cheese microbiota and monitor the presence and viability of starters and probiotic strains. Our findings showed no marked differences for gross composition, total lipids, total cholesterol, and fatty acid levels among all cheeses during ripening. Differently, the multivariate statistical analysis of NMR data highlighted significant variations in the cheese' profiles both in terms of maturation time and strains combination. The use of autochthonous cultures and adjunct probiotic strains did not adversely affect acceptability of the cheeses. Higher levels of lactobacilli (viability of 108-109 cfu/g of cheese) were detected in cheeses made with the addition of probiotic autochthonous strains with respect to control cheese during the whole ripening period, suggesting the adequacy of Caciotta cheese as a carrier for probiotic bacteria delivery.