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International Journal of Molecular... May 2021Imbalances in gut and reproductive tract microbiota composition, known as dysbiosis, disrupt normal immune function, leading to the elevation of proinflammatory... (Review)
Review
Imbalances in gut and reproductive tract microbiota composition, known as dysbiosis, disrupt normal immune function, leading to the elevation of proinflammatory cytokines, compromised immunosurveillance and altered immune cell profiles, all of which may contribute to the pathogenesis of endometriosis. Over time, this immune dysregulation can progress into a chronic state of inflammation, creating an environment conducive to increased adhesion and angiogenesis, which may drive the vicious cycle of endometriosis onset and progression. Recent studies have demonstrated both the ability of endometriosis to induce microbiota changes, and the ability of antibiotics to treat endometriosis. Endometriotic microbiotas have been consistently associated with diminished dominance, as well as the elevated abundance of bacterial vaginosis-related bacteria and other opportunistic pathogens. Possible explanations for the implications of dysbiosis in endometriosis include the Bacterial Contamination Theory and immune activation, cytokine-impaired gut function, altered estrogen metabolism and signaling, and aberrant progenitor and stem-cell homeostasis. Although preliminary, antibiotic and probiotic treatments have demonstrated efficacy in treating endometriosis, and female reproductive tract (FRT) microbiota sampling has successfully predicted disease risk and stage. Future research should aim to characterize the "core" upper FRT microbiota and elucidate mechanisms behind the relationship between the microbiota and endometriosis.
Topics: Dysbiosis; Endometriosis; Female; Humans; Lactobacillus; Microbiota
PubMed: 34073257
DOI: 10.3390/ijms22115644 -
Cancer Cell Nov 2023Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome...
Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types.
Topics: Female; Humans; Lactic Acid; Uterine Cervical Neoplasms; Lactobacillus; Microbiota; Tumor Microenvironment
PubMed: 37863066
DOI: 10.1016/j.ccell.2023.09.012 -
Nutrients Jun 2019Lactobacilli are among the most common microorganisms found in kefir; a traditional fermented milk beverage produced locally in many locations around the world. Kefir... (Review)
Review
Lactobacilli are among the most common microorganisms found in kefir; a traditional fermented milk beverage produced locally in many locations around the world. Kefir has been associated with a wide range of purported health benefits; such as antimicrobial activity; cholesterol metabolism; immunomodulation; anti-oxidative effects; anti-diabetic effects; anti-allergenic effects; and tumor suppression. This review critically examines and assesses these claimed benefits and mechanisms with regard to particular Lactobacillus species and/or strains that have been derived from kefir; as well as detailing further potential avenues for experimentation.
Topics: Humans; Kefir; Lactobacillus; Probiotics; Species Specificity
PubMed: 31159409
DOI: 10.3390/nu11061252 -
The American Journal of Gastroenterology Jul 2021It is unclear whether the alleged efficacy of probiotics in childhood acute gastroenteritis depends on the duration and severity of symptoms before treatment. (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
It is unclear whether the alleged efficacy of probiotics in childhood acute gastroenteritis depends on the duration and severity of symptoms before treatment.
METHODS
Preplanned secondary analysis of 2 randomized placebo-controlled trials in children 3-48 months of age was conducted in 16 emergency departments in North America evaluating the efficacy of 2 probiotic products (Lactobacillus rhamnosus GG and a combination probiotic: L. rhamnosus and L. helveticus). Participants were categorized in severity groups according to the duration (<24, 24-<72, and ≥72 hours) and the frequency of diarrhea episodes in the 24 hours (≤3, 4-5, and ≥6) before presentation. We used regression models to assess the interaction between pretreatment diarrhea severity groups and treatment arm (probiotic or placebo) in the presence of moderate-to-severe gastroenteritis (Modified Vesikari Scale score ≥9). Secondary outcomes included diarrhea frequency and duration, unscheduled healthcare provider visits, and hospitalization.
RESULTS
A total of 1,770 children were included, and 882 (50%) received a probiotic. The development of moderate-to-severe gastroenteritis symptoms after the initiation of treatment did not differ between groups (probiotic-18.4% [162/882] vs placebo-18.3% [162/888]; risk ratio 1.00; 95% confidence interval 0.87, 1.16; P = 0.95). There was no evidence of interaction between baseline severity and treatment (P = 0.61) for the primary or any of the secondary outcomes: diarrhea duration (P = 0.88), maximum diarrheal episodes in a 24-hour period (P = 0.87), unscheduled healthcare visits (P = 0.21), and hospitalization (P = 0.87).
DISCUSSION
In children 3-48 months with acute gastroenteritis, the lack of effect of probiotics is not explained by the duration of symptoms or frequency of diarrheal episodes before presentation.
Topics: Child, Preschool; Diarrhea; Female; Gastroenteritis; Humans; Infant; Lactobacillus helveticus; Lacticaseibacillus rhamnosus; Male; Probiotics; Severity of Illness Index; Time Factors; Treatment Outcome
PubMed: 34183579
DOI: 10.14309/ajg.0000000000001295 -
Microbiome Nov 2022Dysregulation of gut microbiota-associated tryptophan metabolism has been observed in patients with multiple sclerosis. However, defining direct mechanistic links...
BACKGROUND
Dysregulation of gut microbiota-associated tryptophan metabolism has been observed in patients with multiple sclerosis. However, defining direct mechanistic links between this apparent metabolic rewiring and individual constituents of the gut microbiota remains challenging. We and others have previously shown that colonization with the gut commensal and putative probiotic species, Lactobacillus reuteri, unexpectedly enhances host susceptibility to experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. To identify underlying mechanisms, we characterized the genome of commensal L. reuteri isolates, coupled with in vitro and in vivo metabolomic profiling, modulation of dietary substrates, and gut microbiota manipulation.
RESULTS
The enzymes necessary to metabolize dietary tryptophan into immunomodulatory indole derivatives were enriched in the L. reuteri genomes, including araT, fldH, and amiE. Moreover, metabolite profiling of L. reuteri monocultures and serum of L. reuteri-colonized mice revealed a depletion of kynurenines and production of a wide array of known and novel tryptophan-derived aryl hydrocarbon receptor (AhR) agonists and antagonists, including indole acetate, indole-3-glyoxylic acid, tryptamine, p-cresol, and diverse imidazole derivatives. Functionally, dietary tryptophan was required for L. reuteri-dependent EAE exacerbation, while depletion of dietary tryptophan suppressed disease activity and inflammatory T cell responses in the CNS. Mechanistically, L. reuteri tryptophan-derived metabolites activated the AhR and enhanced T cell production of IL-17.
CONCLUSIONS
Our data suggests that tryptophan metabolism by gut commensals, such as the putative probiotic species L. reuteri, can unexpectedly enhance autoimmunity, inducing broad shifts in the metabolome and immunological repertoire. Video Abstract.
Topics: Mice; Animals; Limosilactobacillus reuteri; Autoimmunity; Tryptophan; Multiple Sclerosis; Indoles
PubMed: 36419205
DOI: 10.1186/s40168-022-01408-7 -
MicrobiologyOpen Feb 2021The healthy vaginal microbiota is dominated by Lactobacillus spp., which provide an important critical line of defense against pathogens, as well as giving beneficial...
The healthy vaginal microbiota is dominated by Lactobacillus spp., which provide an important critical line of defense against pathogens, as well as giving beneficial effects to the host. We characterized L. gasseri 1A-TV, L. fermentum 18A-TV, and L. crispatus 35A-TV, from the vaginal microbiota of healthy premenopausal women, for their potential probiotic activities. The antimicrobial effects of the 3 strains and their combination against clinical urogenital bacteria were evaluated together with the activities of their metabolites produced by cell-free supernatants (CFSs). Their beneficial properties in terms of ability to interfere with vaginal pathogens (co-aggregation, adhesion to HeLa cells, biofilm formation) and antimicrobial activity mediated by CFSs were assessed against multidrug urogenital pathogens (S. agalactiae, E. coli, KPC-producing K. pneumoniae, S. aureus, E. faecium VRE, E. faecalis, P. aeruginosa, P. mirabilis, P. vulgaris, C. albicans, C. glabrata). The Lactobacilli tested exhibited an extraordinary ability to interfere and co-aggregate with urogenital pathogens, except for Candida spp., as well as to adhere to HeLa cells and to produce biofilm in the Lactobacillus combination. Lactobacillus CFSs and their combination revealed a strong bactericidal effect on the multidrug resistant indicator strains tested, except for E. faecium and E. faecalis. The antimicrobial activity was maintained after heat treatment but decreased after enzymatic treatment. All Lactobacilli showed lactic dehydrogenase activity and production of D- and L-lactic acid isomers on Lactobacillus CFSs, while only 1A-TV and 35A-TV released hydrogen peroxide and carried helveticin J and acidocin A bacteriocins. These results suggest that they can be employed as a new vaginal probiotic formulation and bio-therapeutic preparation against urogenital infections. Further, in vivo studies are needed to evaluate human health benefits in clinical situations.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Multiple, Bacterial; Female; Humans; Lactobacillus; Probiotics; Vagina
PubMed: 33970542
DOI: 10.1002/mbo3.1173 -
Molecules (Basel, Switzerland) Jul 2019Kefir is a homemade, natural fermented product comprised of a probiotic bacteria and yeast complex. Kefir consumption has been associated with many advantageous...
Kefir is a homemade, natural fermented product comprised of a probiotic bacteria and yeast complex. Kefir consumption has been associated with many advantageous properties to general health, including as an antioxidative, anti-obesity, anti-inflammatory, anti-microbial, and anti-tumor moiety. This beverage is commonly found and consumed by people in the United States of America, China, France, Brazil, and Japan. Recently, the consumption of kefir has been popularized in other countries including Malaysia. The microflora in kefir from different countries differs due to variations in culture conditions and the starter media. Thus, this study was aimed at isolating and characterizing the lactic acid bacteria that are predominant in Malaysian kefir grains via macroscopic examination and 16S ribosomal RNA gene sequencing. The results revealed that the Malaysian kefir grains are dominated by three different strains of Lactobacillus strains, which are Lactobacillus harbinensis, Lactobacillusparacasei, and Lactobacillus plantarum. The probiotic properties of these strains, such as acid and bile salt tolerances, adherence ability to the intestinal mucosa, antibiotic resistance, and hemolytic test, were subsequently conducted and extensively studied. The isolated Lactobacillus spp. from kefir H maintained its survival rate within 3 h of incubation at pH 3 and pH 4 at 98.0 ± 3.3% and 96.1 ± 1.7% of bacteria growth and exhibited the highest survival at bile salt condition at 0.3% and 0.5%. The same isolate also showed high adherence ability to intestinal cells at 96.3 ± 0.01%, has antibiotic resistance towards ampicillin, penicillin, and tetracycline, and showed no hemolytic activity. In addition, the results of antioxidant activity tests demonstrated that isolated Lactobacillus spp. from kefir G possessed high antioxidant activities for total phenolic content (TPC), total flavonoid content (TFC), ferric reducing ability of plasma (FRAP), and 1,1-diphenyl-2-picryl-hydrazine (DPPH) assay compared to other isolates. From these data, all Lactobacillus spp. isolated from Malaysian kefir serve as promising candidates for probiotics foods and beverage since they exhibit potential probiotic properties and antioxidant activities.
Topics: Antioxidants; Humans; Kefir; Lactobacillus; Lactobacillus plantarum; Malaysia; Probiotics
PubMed: 31319614
DOI: 10.3390/molecules24142606 -
The vaginal microbiome and the risk of preterm birth: a systematic review and network meta-analysis.Scientific Reports May 2022Preterm birth is a major cause of neonatal morbidity and mortality worldwide. Increasing evidence links the vaginal microbiome to the risk of spontaneous preterm labour... (Meta-Analysis)
Meta-Analysis
Preterm birth is a major cause of neonatal morbidity and mortality worldwide. Increasing evidence links the vaginal microbiome to the risk of spontaneous preterm labour that leads to preterm birth. The aim of this systematic review and network meta-analysis was to investigate the association between the vaginal microbiome, defined as community state types (CSTs, i.e. dominance of specific lactobacilli spp, or not (low-lactobacilli)), and the risk of preterm birth. Systematic review using PubMed, Web of Science, Embase and Cochrane library was performed. Longitudinal studies using culture-independent methods categorizing the vaginal microbiome in at least three different CSTs to assess the risk of preterm birth were included. A (network) meta-analysis was conducted, presenting pooled odds ratios (OR) and 95% confidence intervals (CI); and weighted proportions and 95% CI. All 17 studies were published between 2014 and 2021 and included 38-539 pregnancies and 8-107 preterm births. Women presenting with "low-lactobacilli" vaginal microbiome were at increased risk (OR 1.69, 95% CI 1.15-2.49) for delivering preterm compared to Lactobacillus crispatus dominant women. Our network meta-analysis supports the microbiome being predictive of preterm birth, where low abundance of lactobacilli is associated with the highest risk, and L. crispatus dominance the lowest.
Topics: Female; Humans; Infant, Newborn; Lactobacillus; Lactobacillus crispatus; Microbiota; Network Meta-Analysis; Pregnancy; Premature Birth; Vagina
PubMed: 35562576
DOI: 10.1038/s41598-022-12007-9 -
Nutrients Apr 2021Probiotics seem to have promising effects in the prevention and treatment of allergic conditions including atopic dermatitis (AD) and food allergy. The purpose of this... (Randomized Controlled Trial)
Randomized Controlled Trial
The Effectiveness of Probiotic and Strains in Children with Atopic Dermatitis and Cow's Milk Protein Allergy: A Multicenter, Randomized, Double Blind, Placebo Controlled Study.
Probiotics seem to have promising effects in the prevention and treatment of allergic conditions including atopic dermatitis (AD) and food allergy. The purpose of this multicenter randomized placebo-controlled trial was to evaluate the effectiveness of a probiotic preparation comprising ŁOCK 0900, ŁOCK 0908, and ŁOCK 0918 in children under 2 years of age with AD and a cow's milk protein (CMP) allergy. The study enrolled 151 children, who-apart from being treated with a CMP elimination diet-were randomized to receive the probiotic preparation at a daily dose of 10 bacteria or a placebo for three months, with a subsequent nine-month follow-up. The primary outcomes included changes in AD symptom severity assessed with the scoring AD (SCORAD) index and in the proportion of children with symptom improvement (a SCORAD score decreased by at least 30% in comparison with that at baseline). After the three-month intervention, both the probiotic and placebo groups showed a significant ( < 0.0001) decrease in SCORAD scores, which was maintained nine months later. The percentage of children who showed improvement was significantly higher in the probiotic than in the placebo group (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.13-5.8; = 0.012) after three months. Probiotics induced SCORAD improvement mainly in allergen sensitized patients (OR 6.03; 95% CI 1.85-19.67, = 0.001), but this positive effect was not observed after nine months. The results showed that the mixture of probiotic ŁOCK strains offers benefits for children with AD and CMP allergy. Further research is necessary to assess the effect of probiotic supplementation on the development of immune tolerance (NCT04738565).
Topics: Allergens; Animals; Cattle; Dermatitis, Atopic; Double-Blind Method; Humans; Infant; Lacticaseibacillus casei; Lacticaseibacillus rhamnosus; Milk Hypersensitivity; Probiotics
PubMed: 33916192
DOI: 10.3390/nu13041169 -
Clinical and Translational Medicine Dec 2021Although microbioa-based therapies have shown putative effects on the treatment of non-alcoholic fatty liver disease (NAFLD), it is not clear how microbiota-derived...
BACKGROUND
Although microbioa-based therapies have shown putative effects on the treatment of non-alcoholic fatty liver disease (NAFLD), it is not clear how microbiota-derived metabolites contribute to the prevention of NAFLD. We explored the metabolomic signature of Lactobacillus lactis and Pediococcus pentosaceus in NAFLD mice and its association in NAFLD patients.
METHODS
We used Western diet-induced NAFLD mice, and L. lactis and P. pentosaceus were administered to animals in the drinking water at a concentration of 10 CFU/g for 8 weeks. NAFLD severity was determined based on liver/body weight, pathology and biochemistry markers. Caecal samples were collected for the metagenomics by 16S rRNA sequencing. Metabolite profiles were obtained from caecum, liver and serum. Human stool samples (healthy control [n = 22] and NAFLD patients [n = 23]) were collected to investigate clinical reproducibility for microbiota-derived metabolites signature and metabolomics biomarker.
RESULTS
L. lactis and P. pentosaceus supplementation effectively normalized weight ratio, NAFLD activity score, biochemical markers, cytokines and gut-tight junction. While faecal microbiota varied according to the different treatments, key metabolic features including short chain fatty acids (SCFAs), bile acids (BAs) and tryptophan metabolites were analogously restored by both probiotic supplementations. The protective effects of indole compounds were validated with in vitro and in vivo models, including anti-inflammatory effects. The metabolomic signatures were replicated in NAFLD patients, accompanied by the comparable levels of Firmicutes/Bacteroidetes ratio, which was significantly higher (4.3) compared with control (0.6). Besides, the consequent biomarker panel with six stool metabolites (indole, BAs, and SCFAs) showed 0.922 (area under the curve) in the diagnosis of NAFLD.
CONCLUSIONS
NAFLD progression was robustly associated with metabolic dys-regulations in the SCFAs, bile acid and indole compounds, and NAFLD can be accurately diagnosed using the metabolites. L. lactis and P. pentosaceus ameliorate NAFLD progression by modulating gut metagenomic and metabolic environment, particularly tryptophan pathway, of the gut-liver axis.
Topics: Animals; Benzofurans; Cellular Reprogramming; Diet, Western; Disease Models, Animal; Feces; Gastrointestinal Microbiome; Lactobacillus; Metabolome; Mice; Non-alcoholic Fatty Liver Disease; Pediococcus pentosaceus; Quinolines
PubMed: 34965016
DOI: 10.1002/ctm2.634