ABSTRACT
Human milk oligosaccharides (HMOs) are an evolutionarily significant advantage bestowed by mothers for facilitating the development of the infant's gut microbiota. They can avoid absorption in the stomach and small intestine, reaching the colon successfully, where they engage in close interactions with gut microbes. This process also enables HMOs to exert additional prebiotic effects, including regulating the mucus layer, promoting physical growth and brain development, as well as preventing and mitigating conditions such as NEC, allergies, and diarrhea. Here, we comprehensively review the primary ways by which gut microbiota, including Bifidobacteria and other genera, utilize HMOs, and we classify them into five central pathways. Furthermore, we emphasize the metabolic benefits of bacteria consuming HMOs, particularly the recently identified intrinsic link between HMOs and the metabolic conversion of tryptophan to indole and its derivatives. We also examine the extensive probiotic roles of HMOs and their recent research advancements, specifically concentrating on the unsummarized role of HMOs in regulating the mucus layer, where their interaction with the gut microbiota becomes crucial. Additionally, we delve into the principal tools used for functional mining of new HMOs. In conclusion, our study presents a thorough analysis of the interaction mechanism between HMOs and gut microbiota, emphasizing the cooperative utilization of HMOs by gut microbiota, and provides an overview of the subsequent probiotic effects of this interaction. This review provides new insights into the interaction of HMOs with the gut microbiota, which will inform the mechanisms by which HMOs function.
Subject(s)
Gastrointestinal Microbiome , Milk, Human , Oligosaccharides , Prebiotics , Humans , Gastrointestinal Microbiome/physiology , Milk, Human/chemistry , Milk, Human/microbiology , Oligosaccharides/chemistry , Probiotics , Infant , Bacteria/metabolism , Bifidobacterium/physiologyABSTRACT
Throughout the life span of a host, bifidobacteria have shown superior colonization and glycan abilities. Complex glycans, such as human milk oligosaccharides and plant glycans, that reach the colon are directly internalized by the transport system of bifidobacteria, cleaved into simple structures by extracellular glycosyl hydrolase, and transported to cells for fermentation. The glycan utilization of bifidobacteria introduces cross-feeding activities between bifidobacterial strains and other microbiota, which are influenced by host nutrition and regulate gut homeostasis. This review discusses bifidobacterial glycan utilization strategies, focusing on the cross-feeding involved in bifidobacteria and its potential health benefits. Furthermore, the impact of cross-feeding on the gut trophic niche of bifidobacteria and host health is also highlighted. This review provides novel insights into the interactions between microbe-microbe and host-microbe.
Subject(s)
Bifidobacterium , Gastrointestinal Microbiome , Homeostasis , Polysaccharides , Humans , Bifidobacterium/metabolism , Bifidobacterium/physiology , Polysaccharides/metabolism , Host Microbial Interactions , Animals , FermentationABSTRACT
Oral administration of probiotics has been proposed as a promising biotherapy to prevent and treat different diseases related to gastrointestinal disorders, such as irritable bowel syndrome (IBS). Due to the increasing research area on the characterisation of new probiotic bacterial strains, it is necessary to perform suitable in vitro experiments, using pertinent cellular models, in order to establish appropriate readout profiles based on IBS symptoms and subtypes. In this work, a collection of 30 candidate strains, belonging mainly to the Lactobacillus and Bifidobacterium genera, were screened using three different sets of in vitro experiments with different readouts to identify promising probiotic strains with: (1) the ability to inhibit the synthesis of IL-8 production by TNF-α stimulated HT-29 cells, (2) immunomodulatory properties quantified as increased IL-10 levels in peripheral blood mononuclear cell (PBMCs), and (3) the ability to maintain epithelial barrier integrity by increasing the trans-epithelial/endothelial electrical resistance (TEER) values in Caco-2 cells. Based on these criteria, three strains were selected: Lactobacillus gasseri PI41, Lacticaseibacillus rhamnosus PI48 and Bifidobacterium animalis subsp. lactis PI50, and tested in a murine model of low-grade inflammation induced by dinitrobenzene sulfonic acid (DNBS), which mimics some of the symptoms of IBS. Among the three strains, L. gasseri PI41 improved overall host well-being by preventing body weight loss in DNBS-treated mice and restored gut homeostasis by normalising the intestinal permeability and reducing pro-inflammatory markers. Therefore, the potential of this strain was confirmed in a second murine model known to reproduce IBS symptoms: the neonatal maternal separation (NMS) model. The PI41 strain was effective in preventing intestinal permeability and reducing colonic hypersensitivity. In conclusion, the set of in vitro experiments combined with in vivo assessments allowed us to identify a promising probiotic candidate strain, L. gasseri PI41, in the context of IBS.
Subject(s)
Irritable Bowel Syndrome , Probiotics , Probiotics/administration & dosage , Probiotics/pharmacology , Irritable Bowel Syndrome/therapy , Irritable Bowel Syndrome/microbiology , Humans , Animals , Mice , Caco-2 Cells , HT29 Cells , Disease Models, Animal , Leukocytes, Mononuclear/immunology , Lactobacillus/physiology , Interleukin-8/metabolism , Bifidobacterium/physiology , Interleukin-10 , Lactobacillus gasseri , Lacticaseibacillus rhamnosus/physiology , Male , Bifidobacterium animalis/physiologyABSTRACT
Despite the anatomical separation, strong evidence suggested a bidirectional association between gut microbiota and central nervous system. Cross-talk between gut microbiota and brain has an important role in the pathophysiology of neurodegenerative disorders and regenerative processes. However, choosing the appropriate probiotics and combination therapy of probiotics to provide a synergistic effect is very crucial. In the present study, we investigated the effect of Lactobacillus casei (L. casei) and Bifidobacterium breve (B. breve) on alternation performance, oxidant/antioxidant biomarkers, the extent of demyelination, and the expression level of HO-1, Nrf-2, Olig2, MBP, PDGFRα, and BDNF in cuprizone (CPZ)-induced demyelination model of rat corpus callosum. In order to induce this model, rats received oral administration of CPZ 0.6% w/w in corn oil for 28 days. Then, L. casei, B. breve, or their combinations were orally administrated for 28 days. Y maze test was performed to investigate the alternation performance. Oxidant/antioxidant biomarkers were determined by colorimetric methods. Extent of demyelination was investigated using FluoroMyelin staining. The genes' expression levels of antioxidant and myelin lineage cells were assessed by quantitative real time PCR. The results showed the probiotics supplementation significantly improve the alternation performance and antioxidant capacity in demyelinated corpus callosum. Interestingly, B. breve supplementation alleviated demyelination and oxidative stress levels more than the administration of L. casei alone or the combination of two probiotics. These observations suggest that B. breve could provide a supplementary strategy for the treatment of multiple sclerosis by increasing antioxidant capacity and remyelination.
Subject(s)
Bifidobacterium breve , Demyelinating Diseases , Lacticaseibacillus casei , Probiotics , Rats , Animals , Cuprizone/toxicity , Antioxidants , Bifidobacterium/physiology , Probiotics/pharmacology , Probiotics/therapeutic use , Oxidative Stress , Demyelinating Diseases/chemically induced , Biomarkers , OxidantsABSTRACT
The widespread use of cyproconazole (CPZ) enhances food security but may pose potential risks to non-target organisms. Therefore, we applied Multi-omics techniques to reveal the response of the intestinal barrier to CPZ exposure and explore whether the Bifidobacterium intervention experiment can repair the damage. First, we found that exposure to CPZ at environmentally relevant concentrations led to intestinal injury phenotype, significantly down-regulated intestinal protein gene expression, and up-regulated pro-inflammatory gene expression, further causing intestinal dysbacteriosis and metabolic disorders. In particular, by combining analysis of gut microbiota and metabolites, we noticed acetate, a key metabolite, which decreased sharply after exposure to high concentration of CPZ. Expectedly, after supplementing with Bifidobacterium (a core bacterium that produces acetate), we noticed that the acetate content was quickly restored. Further, we also verified that the increase in acetate content after Bifidobacterium supplementation at least partially promoted IL-22 secretion, which in turn stimulated the secretion of ß-defensins (zfbd-1, zfbd-2, zfbd-3), thereby repairing the intestinal damage. In conclusion, our work confirms the potential of Bifidobacterium to improve intestinal damage and metabolic dysbiosis caused by CPZ exposure. It provides directional recommendations for the application of probiotics to repair the toxicological risk of pesticide exposure.
Subject(s)
Gastrointestinal Microbiome , Triazoles , Zebrafish , Animals , Bifidobacterium/physiology , Gastrointestinal Microbiome/genetics , AcetatesABSTRACT
The aim of the work was to evaluate antagonistic activity of Lactobacillus spp. and Bifidobacterium spp. in vitro against cariogenic Streptococcus mutans UA 159 and viability in chewing gum, during storage. Antagonistic activity was evaluated in vitro by the "spot on the lawn" test. Two bacteria were chosen and subjected to lyophilization and microencapsulation using the atomization method, containing polyvinylpyrrolidone polymer and lactose as encapsulating agents. For application in food matrices, four treatments were elaborated: chewing gum containing lyophilized B. lactis B94 (BLL), microencapsulated B. lactis B94 (BLE), lyophilized L. brevis (LBL), and microencapsulated L. brevis (LBE). Both microorganisms demonstrated a high capacity for inhibition against S. mutans, when compared to oral antiseptic chlorhexidine 0.2% in vitro, and according to the test of sensitivity profile to proteolytic enzymes, all the bacteria tested are producers of antimicrobial peptides, resulting in the inhibitory activity of the cariogenic bacterium. Furthermore, the viability of B. lactis B94 and L. brevis was maintained after microencapsulation, indicating that the process was efficient, with no significant difference (p < 0.05) between the results. And, in the chewing gum containing the bacteria during the storage period (33 days), it was found that cell immobilization did not significantly influence (p < 0.05) the counts of L. brevis but benefited the viability of B. lactis B94. Therefore, both probiotic bacteria are producers of antimicrobial substances with the ability to inhibit S. mutans, in vitro. The microencapsulation was considered efficient since it influenced the viability of B. lactis B94 (> 8 log CFU/g); however, the microencapsulation did not influence the viability of L. brevis since in both lyophilized and encapsulated form; the concentration of the bacteria remained above 8 log CFU/g during the storage period of the chewing gum.
Subject(s)
Probiotics , Streptococcus mutans , Lactobacillus/physiology , Chewing Gum , Bifidobacterium/physiology , Probiotics/pharmacologyABSTRACT
Gut microbiota dysbiosis with increased pathogenic bacteria and decreased beneficial bacteria is associated with colorectal cancer (CRC) development. This study examined the effect of a newly developed probiotic formula in modulating CRC-related bacteria. We developed a probiotic formula containing three bifidobacteria (B. adolescentis, B. longum, and B. bifidum) based on the identification of bacterial species that showed significant correlations with CRC-related bacteria including Fusobacterium nucleatum (Fn), Lachnoclostridium sp. m3, Clostridium hathewayi (Ch), and Bacteroides clarus (Bc). We co-cultured Fn with each bifidobacterium or the combined formula and examined the growth of Fn by qPCR. The three individual bifidobacteria significantly inhibited the growth of Fn compared to the control treatment (24~65% inhibition; all p < 0.001). The combination of the three bifidobacteria showed a greater inhibitory effect on Fn growth (70% inhibition) than the individual bifidobacteria (all p < 0.05). We further examined the effect of the probiotic formula in a pilot study of 72 subjects (40 on probiotics; 32 with no intervention) for 4 weeks and followed them up for 12 weeks. The relative fecal abundances of the bifidobacteria in the formula and the CRC-related markers (Fn, m3, Ch, and Bc) were quantitated by qPCR before and after the intervention, and the combined CRC risk score (4Bac; Fn, m3, Ch, and Bc) was evaluated. Subjects with probiotics intervention showed significantly increased abundances of the bifidobacteria from week 2 to week 5 compared to baseline (p < 0.05), and the abundances dropped to baseline levels after the cessation of the intervention. There were significant decreases in the levels of CRC-related markers (Fn and m3) and the CRC risk score (4Bac) from week 2 to week 12 compared to baseline levels (p < 0.05) in the intervention group but not in the control group. A novel probiotic formula containing B. adolescentis, B. longum, and B. bifidum was effective in inhibiting the growth of F. nucleatum in vitro and improving the gut microbial environment against CRC development.
Subject(s)
Colorectal Neoplasms , Probiotics , Humans , Pilot Projects , Probiotics/therapeutic use , Feces/microbiology , Bifidobacterium/physiologyABSTRACT
BACKGROUND AND AIM: Disturbance of gut microbiota is associated with pathological change in multiple diseases. Probiotics can improve symptoms and exert clinical effects via regulation of gastrointestinal microecological environments, and a probiotic product commonly dispensed by Chinese physicians is a combination of live Bifidobacterium, Lactobacillus, and Enterococcus in powder/capsule form. It contains three strains-of Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis-which can act synergistically to balance the microbiome, regulate immunity, and repair the gut barrier. Although this product has been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat digestive system diseases. To date, there have been no reference standards to guide clinical practice and no relevant expert consensus on this product, in China. METHODS: Following a literature search, evidence was graded and classified according to the grading of recommendations assessment, development, and evaluation (GRADE) system and consensus was secured from a panel of 52 experts. RESULTS: An expert consensus has been formed, on the clinical application of live combined Bifidobacterium, Lactobacillus, and Enterococcus in various digestive system diseases, to provide reference for its clinical use. CONCLUSIONS: Bifidobacterium triple viable powder/capsule may offer benefits, by regulating the balance of intestinal microecology. It can be used for the treatment and prevention of various digestive system diseases with good overall safety; further research is needed to confirm its application in other contexts. The recommendations in this consensus will be confirmed or refined in light of future research and clinical practice.
Subject(s)
Digestive System Diseases , Probiotics , Humans , Bifidobacterium/physiology , Consensus , East Asian People , Enterococcus , Lactobacillus/physiology , Powders , Probiotics/therapeutic use , Capsules , Gastrointestinal MicrobiomeABSTRACT
B. longum subsp. infantis is a subspecies of Bifidobacterium longum, and very few strains are shown to have immunomodulatory effects. In the present study, the improvement of dextran sulphate sodium (DSS)-induced colitis by four B. longum subsp. infantis strains was compared. The results showed that B. longum subsp. infantis FJSYZ1M3 could significantly decrease disease activity index (DAI), inhibit weight loss and colon shortening, and attenuate colon tissue damage in DSS-induced colitis mice. And B. longum subsp. infantis FJSYZ1M3 intervention improved the integrity of intestinal tight junctions, relieved mucus layer damage and inhibited epithelial cell apoptosis, thereby maintaining the intestinal barrier. Additionally, B. longum subsp. infantis FJSYZ1M3 significantly affected the levels of inflammatory cytokines IL-6, IL-1ß, and IL-10 in the colon, thus relieving inflammation in colitis mice. Furthermore, B. longum subsp. infantis FJSYZ1M3 could ameliorate gut microbiota disturbance caused by DSS exposure and increase the level of butyric acid in cecal contents. In general, these findings suggested that B. longum subsp. infantis FJSYZ1M3 alleviated DSS-induced colitis by maintaining the intestinal barrier, regulating inflammatory cytokines, and modifying the gut microbiota.
Subject(s)
Bifidobacterium longum , Colitis , Gastrointestinal Microbiome , Mice , Animals , Cytokines , Bifidobacterium/physiology , Colitis/chemically induced , Colitis/microbiology , Bifidobacterium longum subspecies infantis , Colon , Dextran Sulfate/adverse effects , Mice, Inbred C57BL , Disease Models, AnimalABSTRACT
A growing body of research studies the relationship between probiotic bacteria in the gut and the host organism, including the impact on cognitive functioning. Data from human studies are scarce; however, recent studies point toward the beneficial role of probiotics for cognitive functioning. One of the mechanisms involved in this relationship is the probiotic's ability to influence inflammation and immune response. The aim of this initial study was to investigate the effects of probiotic supplementation with Bifidobacterium Lactis BS01 and Lactobacillus Acidophilus LA02 on cognitive functioning in healthy, young adult females. A total of 53 participants aged 19-31 were enrolled, and 38 completed the trial. A 6-week probiotic or placebo treatment was conducted. Five measures of cognitive functioning were applied pre- and post-treatment. Both groups showed general improvement at the second assessment. Contrary to our hypothesis, the placebo group improved slightly, but significantly, in four out of five measures of cognitive functioning, with the exception of the Wisconsin Card Sorting Test (WCST). The supplementation group improved significantly in two measures of the WCST, compared to the placebo group. Similar results have been previously reported. Probiotic supplementation, while not harmful, might not be beneficial for cognition in the healthy population, or at least not universally.
Subject(s)
Bifidobacterium animalis , Probiotics , Female , Humans , Young Adult , Bifidobacterium/physiology , Cognition , Double-Blind Method , Lactobacillus acidophilus/physiology , Probiotics/pharmacology , Probiotics/therapeutic useABSTRACT
Previous works have described the activity of Bifidobacterium longum subsp. infantis CECT 7210 (also commercially named B. infantis IM-1®) against rotavirus in mice and intestinal pathogens in piglets, as well as its diarrhea-reducing effect on healthy term infants. In the present work, we focused on the intestinal immunomodulatory effects of B. infantis IM-1® and for this purpose we used the epithelial cell line isolated from colorectal adenocarcinoma Caco-2 and a co-culture system of human dendritic cells (DCs) from peripheral blood together with Caco-2 cells. Single Caco-2 cultures and Caco-2: DC co-cultures were incubated with B. infantis IM-1® or its supernatant either in the presence or absence of Escherichia coli CECT 515. The B. infantis IM-1® supernatant exerted a protective effect against the cytotoxicity caused by Escherichia coli CECT 515 on single cultures of Caco-2 cells as viability reached the values of untreated cells. B. infantis IM-1® and its supernatant also decreased the secretion of pro-inflammatory cytokines by Caco-2 cells and the co-cultures incubated in the presence of E. coli CECT 515, with the response being more modest in the latter, which suggests that DCs modulate the activity of Caco-2 cells. Overall, the results obtained point to the immunomodulatory activity of this probiotic strain, which might underlie its previously reported beneficial effects.
Subject(s)
Escherichia coli Infections , Probiotics , Animals , Bifidobacterium/physiology , Bifidobacterium longum subspecies infantis/metabolism , Caco-2 Cells , Cytokines/metabolism , Escherichia coli/metabolism , Humans , Infant , Mice , Probiotics/pharmacology , SwineABSTRACT
We evaluated the potential of whey protein hydrolysate as a lyoprotectant for maintaining the cell viability of Bifidobacterium animalis ssp. lactis Probio-M8 during freeze-drying and subsequent storage. The moisture content and water activity of the lyophilized samples treated by different concentrations of whey protein hydrolysate were ≤5.23 ± 0.33 g/100 g and ≤0.102 ± 0.003, respectively. During storage at 25°C and 30°C, whey protein hydrolysate had a stronger protective effect on B. lactis Probio-M8 than the same concentration of whey protein. Using the Excel tool GinaFit, we estimated the microbial inactivation kinetics during storage. Whey protein hydrolysate reduced cell damage caused by an increase in temperature. Whey protein hydrolysate could protect cells by increasing the osmotic pressure as a compatible solute. Whey protein hydrolysate improved cell membrane integrity and reduced the amounts of reactive oxygen species and malondialdehyde produced. The findings indicated that whey protein hydrolysate was a novel antioxidant lyoprotectant that could protect probiotics during freeze-drying and storage.
Subject(s)
Bifidobacterium animalis , Probiotics , Bifidobacterium/physiology , Freeze Drying/veterinary , Probiotics/metabolism , Protein Hydrolysates/pharmacology , WheyABSTRACT
Objective: To investigate the effect of Bifidobacterium animalis B94 on the prevention and treatment of liver injury in rats and to elucidate the underlying mechanism of this relationship. Methods: Specific pathogen-free (SPF) rats were selected as the healthy control group, liver injury group and B94 treatment group, with 6 rats in each group. After the model was established, the experimental animals were tested for serum liver function indicators, gut microbiota composition, metabolite composition, and histopathology. Results: The albumin/globulin ratio and serum TBA, alanine aminotransferase, aspartate aminotransferase, and indirect bilirubin levels in the B94 treatment group were significantly lower than those in the liver injury group. 16S rRNA analysis showed that the gut microbiota of the three groups of rats were significantly different. Metabolic profile analysis showed that there were significant differences in the gut metabolomes of the three groups. Haematoxylin-eosin staining of the intestinal mucosa and liver tissues showed that the degree of liver and intestinal tissue damage in the B94 treatment group was significantly lower than that in the liver injury group. Conclusion: Bifidobacterium animalis B94 can affect the process of liver injury in rats by improving liver function, reducing intestinal damage, and regulating gut microbiota and metabolite production.
Subject(s)
Bifidobacterium animalis , Probiotics , Animals , Bifidobacterium/physiology , Bifidobacterium animalis/genetics , Liver , RNA, Ribosomal, 16S/genetics , RatsABSTRACT
Early life stress can considerably interfere in gut microbiome formation and nervous system development. Specific probiotic strains have been proved to exert anti-stress effects by modulating the gut-brain axis. However, little is known about whether probiotic treatment during pregnancy can protect the offspring from early life stress. In this study, Bifidobacterium breve CCFM1025, previously proven to exert microbial and neurobiological regulation effects, was given to pregnant mice. The offspring's gut and brain functions were evaluated when challenged with maternal separation. Intriguingly, treatment with probiotics during pregnancy protected the offspring from maternal separation-induced neurobiological and gastrointestinal disorders such as depression-like behaviour and delayed defecation. Quantification of CCFM1025 was performed, and perinatal transmission of CCFM1025 was further validated, which also explained the reason for increased levels of colonic 5-hydroxytryptamine and caecal short-chain fatty acids in the offspring. Our findings indicated that the effects of probiotics can be perinatally transmitted through gut microbes and that probiotic treatment during pregnancy may have great potential in managing health risks in early life.
Subject(s)
Gastrointestinal Diseases , Probiotics , Stress, Psychological , Animals , Female , Mice , Pregnancy , Bifidobacterium/physiology , Gastrointestinal Motility , Infectious Disease Transmission, Vertical , Maternal Deprivation , Probiotics/pharmacologyABSTRACT
Inflammatory bowel disease (IBD) has become a global public health problem. Although the pathogenesis of the disease is unknown, a potential association between the gut microbiota and inflammatory signatures has been established. Probiotics, especially Lactobacillus or Bifidobacterium, are orally taken as food supplements or microbial drugs by patients with IBD or gastrointestinal disorders due to their safety, efficacy, and power to restore the gut microenvironment. In the current study, we investigated the comprehensive effects of probiotic bacterial consortia consisting of Lactobacillus reuteri, Lactobacillus gasseri, Lactobacillus acidophilus (Lactobacillus spp.), and Bifidobacterium lactis (Bifidobacterium spp.) or their metabolites in a dextran sodium sulfate (DSS)-induced colitis mouse model. Our data demonstrate that probiotic consortia not only ameliorate the disease phenotype but also restore the composition and structure of the gut microbiota. Moreover, the effect of probiotic consortia is better than that of any single probiotic strain. The results also demonstrate that mixed fermentation metabolites are capable of ameliorating the symptoms of gut inflammation. However, the administration of metabolites is not as effective as probiotic consortia with respect to phenotypic characteristics, such as body weight, disease activity index (DAI), and histological score. In addition, mixed metabolites led only to changes in intestinal flora composition. In summary, probiotic consortia and metabolites could exert protective roles in the DSS-induced colitis mouse model by reducing inflammation and regulating microbial dysbiosis. These findings from the current study provide support for the development of probiotic-based microbial products as an alternative therapeutic strategy for IBD. IMPORTANCE IBD is a chronic nonspecific inflammatory disease. IBD is characterized by a wide range of lesions, often involving the entire colon, and is characterized mainly by ulcers and erosions of the colonic mucosa. In the present study, we investigated the efficacy of probiotics on the recovery of gut inflammation and the restoration of gut microecology. We demonstrate that probiotic consortia have a superior effect in inhibiting inflammation and accelerating recovery compared with the effects observed in the control group or groups administered with a single strain. These results support the utilization of probiotic consortia as an alternative therapeutic approach to treat IBD.
Subject(s)
Colitis , Inflammatory Bowel Diseases , Probiotics , Animals , Bifidobacterium/physiology , Colitis/drug therapy , Colitis/therapy , Colon/microbiology , Dextran Sulfate/adverse effects , Disease Models, Animal , Inflammation/pathology , Inflammatory Bowel Diseases/therapy , Lactobacillus/physiology , Mice , Probiotics/pharmacology , Probiotics/therapeutic useABSTRACT
BACKGROUND: Oral administration of health-promoting bacteria is increasingly used in clinical practise. These bacteria have anti-inflammatory characteristics and modulate the immune system without major reported side effects. The mechanisms of action are not yet fully defined. Our aim was to study systemic effects of probiotics by measurements of leukocytes as well as local effects on rectal mucosal biopsies after adding a standardized inflammatory stimulus in vitro. METHODS: Fourteen healthy subjects were randomized to receive 1010 colony forming units/day orally of the probiotic strain Lactiplantibacillus plantarum 299 (Lp299), n = 7, or Bifidobacterium infantis CURE21 (CURE21), n = 7, for six weeks. Rectal biopsies were taken before and after ingestion of either probiotic strain product, for stimulation in vitro with tumour necrosis factor alpha (TNF-α) at 10 and 100 ng/ml respectively up to 8 h. Blood tests were sampled before and after treatment. Lactate dehydrogenase (LDH) confirmed viable tissue. RESULTS: Composition of the intestinal microbiota was not changed. Systemic leukocytes decreased after administration of CURE21 (P<0.05) and Lp299 (P<0.01). Levels of the pro-inflammatory cytokine IL-6 in rectal mucosa after stimulation with TNF-α were attenuated after ingestion of Lp299. No effect was seen with CURE21. CONCLUSIONS: Administration of these probiotic strains to healthy humans show both a systemic and local reduction of inflammatory response by lowering leukocyte counts, and for Lp299 IL-6 levels in rectal mucosa. Probiotics may play an important role in the reduction of inflammatory responses expected after trauma during surgery or after pelvic irradiation. Trial registration Clinical Trials, registration number NCT01534572, retrospectively registered ( http://www.clinicaltrials.gov ).
Subject(s)
Gastrointestinal Microbiome , Probiotics , Bifidobacterium/physiology , Cytokines , Humans , Intestinal Mucosa , Leukocytes , Probiotics/therapeutic useABSTRACT
Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.
Subject(s)
Diet , Gastrointestinal Microbiome , Gastrointestinal Tract/microbiology , Genetic Variation , Host Microbial Interactions , Polymorphism, Single Nucleotide , ABO Blood-Group System/genetics , Bifidobacterium/physiology , Clostridiales/physiology , Cohort Studies , Colorectal Neoplasms/genetics , Colorectal Neoplasms/microbiology , Depressive Disorder, Major/genetics , Depressive Disorder, Major/microbiology , Dietary Fiber , Enterococcus faecalis/physiology , Gastrointestinal Microbiome/genetics , Genome-Wide Association Study , Humans , Lactase/genetics , Mediator Complex/genetics , Mendelian Randomization Analysis , Metagenome , Morganella/physiologyABSTRACT
Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10-10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.
Subject(s)
ABO Blood-Group System/genetics , Bacterial Physiological Phenomena , Gastrointestinal Microbiome , Gastrointestinal Tract/microbiology , Genetic Variation , Host Microbial Interactions , Lactase/genetics , Bifidobacterium/physiology , Diet , Fucosyltransferases/genetics , Genome, Human , Genome-Wide Association Study , Humans , Metabolic Networks and Pathways , Metagenome , Multifactorial Inheritance , Netherlands , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Sodium Chloride, Dietary , Triglycerides/blood , Galactoside 2-alpha-L-fucosyltransferaseABSTRACT
This study was designed to explore the therapeutics and the mechanisms of a patented and marked gastric acid and intestine juice-resistant probiotics Bifidobacterium lactis BL-99 (B. lactis BL-99) on the intestinal inflammation and functions in the zebrafish models. After feeding for 6 hours, B. lactis BL-99 was fully retained in the larval zebrafish intestinal tract and stayed for over 24 hours. B. lactis BL-99 promoted the intestinal motility and effectively alleviated aluminum sulfate-induced larval zebrafish constipation (p < 0.01). Irregular high glucose diet induced adult zebrafish intestinal functional and metabolic disorders. After fed with B. lactis BL-99, IL-1ß gene expression was significantly down-regulated, and IL-10 and IL-12 gene levels were markedly up-regulated in this model (p < 0.05). The intestinal lipase activity was elevated in the adult zebrafish intestinal functional disorder model after B. lactis BL-99 treatment (p < 0.05), but tryptase content had no statistical changes (p > 0.05). B. lactis BL-99 improved the histopathology of the adult zebrafish intestinal inflammation, increased the goblet cell numbers, and up-and-down metabolites were markedly recovered after treatment of B. lactis BL-99 (p < 0.05). These results suggest that B. lactis BL-99 could relieve intestinal inflammation and promote intestinal functions, at least in part, through modulating intestinal and microbial metabolism to maintain intestinal health.
Subject(s)
Bifidobacterium/physiology , Inflammation/therapy , Intestines/metabolism , Probiotics/therapeutic use , Alum Compounds/toxicity , Animals , Constipation/chemically induced , Constipation/pathology , Constipation/therapy , Discriminant Analysis , Disease Models, Animal , Down-Regulation/drug effects , Gastrointestinal Motility/drug effects , Glucose/pharmacology , Inflammation/chemically induced , Inflammation/pathology , Interleukin-10/genetics , Interleukin-10/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Intestines/microbiology , Intestines/pathology , Larva/drug effects , Larva/metabolism , Probiotics/pharmacology , Up-Regulation/drug effects , Zebrafish/growth & developmentABSTRACT
OBJECTIVE: Probiotics participate in regulating oral microbiota and reducing the prevalence of oral diseases; however, clinical research on probiotics is insufficient. Therefore, in this study, we performed in vitro screening of potential oral protective probiotic strains and then evaluated the clinical efficacy of the selected strains on maintaining oral health. MATERIALS AND METHODS: Fifty healthy individuals were recruited and randomly assigned into the placebo group and probiotics group, which included three strains of probiotics, Lactobacillus salivarius subs. salicinius AP-32, Lactobacillus paracasei ET-66, and Lactobacillus plantarum LPL28. Each group was blindly administered placebo or probiotics for four weeks. RESULTS: Next-generation sequencing results showed that the oral microbiota of Lactobacillus salivarius in the oral cavity were significantly increased in subjects supplemented with mixed probiotic lozenges. The anti-bacterial activities of viable probiotics were observed within two weeks. Both IgA levels and Lactobacillus and Bifidobacterium abundances in the oral cavity were significantly increased in the experimental groups, along with a reduced formation of plaque. Most participants reported that their oral health conditions and intestinal symptoms had improved. CONCLUSIONS: Overall, our clinical study suggests that oral probiotic lozenges may enhance oral immunity, modulate oral microbiota, and improve oral health.