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Nature Microbiology Mar 2021The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics; however, the multi-omics characteristics of antitumour bacterial...
The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics; however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-γ, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites.
Topics: Animals; Bifidobacterium bifidum; Carcinoma, Non-Small-Cell Lung; Drug Therapy, Combination; Gastrointestinal Microbiome; Humans; Immune Checkpoint Inhibitors; Interferon-gamma; Lung Neoplasms; Metabolome; Mice; Neoplasms, Experimental; Probiotics; Species Specificity; Transcriptome; Tryptophan; Tumor Burden
PubMed: 33432149
DOI: 10.1038/s41564-020-00831-6 -
Microorganisms Nov 2019Bifidobacteria typically represent the most abundant bacteria of the human gut microbiota in healthy breast-fed infants. Members of the species constitute one of the... (Review)
Review
Bifidobacteria typically represent the most abundant bacteria of the human gut microbiota in healthy breast-fed infants. Members of the species constitute one of the dominant taxa amongst these bifidobacterial communities and have been shown to display notable physiological and genetic features encompassing adhesion to epithelia as well as metabolism of host-derived glycans. In the current review, we discuss current knowledge concerning particular biological characteristics of the species that support its specific adaptation to the human gut and their implications in terms of supporting host health.
PubMed: 31717486
DOI: 10.3390/microorganisms7110544 -
The Lancet. Gastroenterology &... Jul 2020Bifidobacterium bifidum MIMBb75 is one of a few probiotic strains that have been shown to be effective in the treatment of irritable bowel syndrome (IBS) and its... (Randomized Controlled Trial)
Randomized Controlled Trial
Heat-inactivated Bifidobacterium bifidum MIMBb75 (SYN-HI-001) in the treatment of irritable bowel syndrome: a multicentre, randomised, double-blind, placebo-controlled clinical trial.
BACKGROUND
Bifidobacterium bifidum MIMBb75 is one of a few probiotic strains that have been shown to be effective in the treatment of irritable bowel syndrome (IBS) and its symptoms. Non-viable strains might have advantages over viable bacteria for product stability and standardisation, as well as for tolerability because safety concerns have been raised for specific patient groups who are susceptible to infection. We aimed to assess the efficacy of non-viable, heat-inactivated (HI) B bifidum MIMBb75 (SYN-HI-001) in the treatment of IBS and its symptoms.
METHODS
We did a double-blind, placebo-controlled trial in which patients with IBS were recruited from 20 study sites in Germany and randomly assigned to receive either two placebo capsules or two capsules with a combined total of 1 × 10 non-viable B bifidum HI-MIMBb75 cells to be taken orally once a day for 8 weeks. Eligible patients were diagnosed with IBS according to Rome III criteria and had abdominal pain (≥4 on an 11-point numerical rating scale) on at least 2 days during a 2-week run-in phase. Patients with chronic inflammatory bowel diseases, systemic diseases, cancer, autoimmune diseases, with an intake of antipsychotic medications 3 months before study start, or with an intake of systemic corticosteroids within 1 month before study start were excluded. Randomisation was in a 1:1 ratio according to a computer-generated blocked list. Patients, investigators, clinical monitors, project managers, and statisticians were masked to the randomisation. The primary composite endpoint was the combination of at least 30% improvement of abdominal pain and adequate relief of overall IBS symptoms being fulfilled in at least 4 of 8 weeks during treatment. Analysis of the primary endpoint included all randomly assigned patients receiving at least one dose of study medication and who had no severe protocol violation. Safety analysis included all patients who had taken at least one dose of the study medication and was based on frequency and severity of adverse events, laboratory evaluation, and global assessment of tolerability. This trial is registered with the ISRCTN registry, ISRCTN14066467, and is completed: the results shown here represent the final analysis.
FINDINGS
Patients were screened between April 15, 2016, and Feb 3, 2017, and 443 patients were allocated to the placebo group (n=222) or the B bifidum HI-MIMBb75 group (n=221). The composite primary endpoint was reached by 74 (34%) of 221 patients in the B bifidum HI-MIMBb75 group compared with 43 (19%) of 222 in the placebo group (risk ratio 1·7, 95% CI 1·3-2·4; p=0·0007). No serious adverse events occurred in the B bifidum HI-MIMBb75 group; seven adverse events suspected to be related to the study product were reported in the B bifidum HI-MIMBb75 group as were eight in the placebo group. No deaths were reported in this study. The most common reported adverse event with a suspected relationship to the study product was abdominal pain, which was reported in two (<1%) patients in the B bifidum HI-MIMBb75 group and one (<1%) in the placebo group. Tolerability was rated as very good or good by 200 (91%) patients in the B bifidum HI-MIMBb75 group compared with 191 (86%) in the placebo group.
INTERPRETATION
This study shows that B bifidum HI-MIMBb75 substantially alleviates IBS and its symptoms in a real-life setting. These results indicate that specific beneficial bacterial effects are mediated independently of cell viability.
FUNDING
Synformulas.
Topics: Abdominal Pain; Adult; Bifidobacterium bifidum; Case-Control Studies; Double-Blind Method; Female; Germany; Humans; Intestines; Irritable Bowel Syndrome; Male; Middle Aged; Pain Measurement; Placebos; Probiotics; Safety; Treatment Outcome
PubMed: 32277872
DOI: 10.1016/S2468-1253(20)30056-X -
Frontiers in Microbiology 2014Bifidobacteria are considered dominant and for this reason key members of the human gut microbiota, particularly during the first one to two years following birth. A... (Review)
Review
Bifidobacteria are considered dominant and for this reason key members of the human gut microbiota, particularly during the first one to two years following birth. A substantial proportion of the bifidobacterial population in the intestine of infants belong to the Bifidobacterium bifidum taxon, whose members have been shown to display remarkable physiological and genetic features involving adhesion to epithelia, as well as utilization of host-derived glycans. Here, we reviewed the current knowledge on the genetic features and associated adaptations of B. bifidum to the human gut.
PubMed: 25191315
DOI: 10.3389/fmicb.2014.00437 -
Biochemical and Biophysical Research... May 2022An increasing number of studies have indicated that alterations in gut microbiota affect brain function, including cognition and memory ability, via the gut-brain axis....
An increasing number of studies have indicated that alterations in gut microbiota affect brain function, including cognition and memory ability, via the gut-brain axis. In this study, we aimed to determine the protective effect of Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) on age-related brain damage in mice. We found that administration of B. bifidum BGN4 and B. longum BORI effectively elevates brain-derived neurotrophic factor expression which was mediated by increased histone 3 lysine 9 trimethylation. Furthermore, administration of probiotic supplementation reversed the DNA damage and apoptotic response in aged mice and also improved the age-related cognitive and memory deficits of these mice. Taken together, the present study highlights the anti-aging effects of B. bifidum BGN4 and B. longum BORI in the aged brain and their beneficial effects for age-related brain disorders.
Topics: Animals; Bifidobacterium bifidum; Bifidobacterium longum; Gastrointestinal Microbiome; Mice; Probiotics; Rejuvenation
PubMed: 35278878
DOI: 10.1016/j.bbrc.2022.03.024 -
Microorganisms Mar 2020Certain species of the genus represent human symbionts. Many studies have shown that the establishment of symbiosis with such bifidobacterial species confers various... (Review)
Review
Certain species of the genus represent human symbionts. Many studies have shown that the establishment of symbiosis with such bifidobacterial species confers various beneficial effects on human health. Among the more than ten (sub)species of human gut-associated that have significantly varied genetic characteristics at the species level, is unique in that it is found in the intestines of a wide age group, ranging from infants to adults. This species is likely to have adapted to efficiently degrade host-derived carbohydrate chains, such as human milk oligosaccharides (HMOs) and mucin -glycans, which enabled the longitudinal colonization of intestines. The ability of this species to assimilate various host glycans can be attributed to the possession of an adequate set of extracellular glycoside hydrolases (GHs). Importantly, the polypeptides of those glycosidases frequently contain carbohydrate-binding modules (CBMs) with deduced affinities to the target glycans, which is also a distinct characteristic of this species among members of human gut-associated bifidobacteria. This review firstly describes the prevalence and distribution of in the human gut and then explains the enzymatic machinery that has developed for host glycan degradation by referring to the functions of GHs and CBMs. Finally, we show the data of co-culture experiments using host-derived glycans as carbon sources, which underpin the interesting altruistic behavior of this species as a cross-feeder.
PubMed: 32231096
DOI: 10.3390/microorganisms8040481 -
Nano Letters Mar 2022There is substantial interest regarding the understanding and designing of nanoengineered bacteria to combat various fatal diseases. Here, we report the nanoengineering...
There is substantial interest regarding the understanding and designing of nanoengineered bacteria to combat various fatal diseases. Here, we report the nanoengineering of using Cremophor EL to encapsulate organic dye molecules by simple incubation and washing processes while maintaining the bacterial morphology and viability. The prepared functional bacteria exhibit characteristics such as optical absorbance, unique fluorescence, powerful photothermal conversion, low toxicity, excellent tumor targeting, and anticancer efficacy. They also displayed significant fluorescent expression in implanted colorectal cancerous tumors. Moreover, the powerful photothermal conversion of the functional bacteria could be spatiotemporally evoked by biologically penetrable near-infrared laser for effective tumor regression in mice, with the help of immunological responses. Our study demonstrates that a nanoengineering approach can provide the strong physicochemical traits and attenuation of living bacterial cells for cancer immunotheranostics.
Topics: Animals; Bifidobacterium bifidum; Cell Line, Tumor; Fluorescence; Mice; Nanoparticles; Neoplasms; Optical Rotation; Phototherapy
PubMed: 35179380
DOI: 10.1021/acs.nanolett.1c04037 -
Journal of Agricultural and Food... Feb 2023In this study, the effectors and mechanisms of FL-276.1 and FL-228.1 in alleviating dextran sulfate sodium (DSS)-induced colitis were investigated. Both FL-276.1 and...
In this study, the effectors and mechanisms of FL-276.1 and FL-228.1 in alleviating dextran sulfate sodium (DSS)-induced colitis were investigated. Both FL-276.1 and FL-228.1 significantly alleviated DSS-induced colitis, whether they were supplemented from the beginning of the experiment (whole course intervention) or after the DSS induction started (partial intervention). Aryl hydrocarbon receptor (AHR) and the nuclear factor erythroid 2-related factor 2 (NRF2) pathways were activated in mice colons, while the NLR family pyrin domain containing 3 (NLRP3) was downregulated under the whole course intervention modes. Indole-3-lactic acid, an AHR ligand produced by FL-276.1 and FL-228.1, could regulate the AHR/NRF2/NLRP3 pathway in Caco-2 monolayers, thus upregulating the tight junction proteins and protecting the integrity of the epithelial barrier. These results are conducive to promoting clinical trials and product development of probiotics for alleviating colitis.
Topics: Animals; Humans; Mice; Bifidobacterium bifidum; Caco-2 Cells; Colitis; Dextran Sulfate; Disease Models, Animal; Inflammasomes; Mice, Inbred C57BL; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; Receptors, Aryl Hydrocarbon
PubMed: 36633059
DOI: 10.1021/acs.jafc.2c06894 -
International Journal of Nanomedicine 2021Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for (BF) to colonize. The anaerobe BF...
PURPOSE
Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer.
METHODS
We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF . Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor.
RESULTS
The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chemotherapy, this therapy not only inhibits tumor growth, but also significantly prolongs the survival time of mice. More importantly, this treatment strategy has no obvious side effects.
CONCLUSION
We successfully established a novel therapy method, BF-mediated HIFU ablation, which provides an excellent platform for highly efficient and non-invasive therapy of tumor.
Topics: Animals; Bifidobacterium bifidum; Cell Line, Tumor; Drug Carriers; Fluorocarbons; Humans; Mice; Nanoparticles; Polyesters
PubMed: 34267516
DOI: 10.2147/IJN.S315650 -
Journal of Agricultural and Food... Sep 2022Bifidobacteria are important mediators of immune system development within the gastrointestinal system and immunological homeostasis. The present study explored the...
Bifidobacteria are important mediators of immune system development within the gastrointestinal system and immunological homeostasis. The present study explored the anti-colitic activity of H3-R2 in a murine dextran sulfate sodium (DSS)-induced model of ulcerative colitis (UC). Moreover, this study offers novel insight regarding the molecular basis for the probiotic properties of H3-R2 by analyzing the underlying mechanisms whereby H3-R2-derived proteins affect the intestinal barrier. H3-R2 administration was sufficient to alleviate clinical manifestations consistent with DSS-induced colitis, restoring aberrant inflammatory cytokine production, enhancing tight junction protein expression, and positively impacting overall intestinal microecological homeostasis in these animals. Moreover, the bifidobacteria-derived GroEL and transaldolase (TAL) proteins were found to regulate tight junction protein expression via the NF-κB, myosin light chain kinase (MLCK), RhoA/Rho-associated protein kinase (ROCK), and mitogen-activated protein kinase (MAPK) signaling pathways, preventing the lipopolysaccharide (LPS)-mediated disruption of the intestinal epithelial cell barrier.
Topics: Animals; Bifidobacterium; Bifidobacterium bifidum; Colitis; Colitis, Ulcerative; Colon; Cytokines; Dextran Sulfate; Disease Models, Animal; Intestinal Mucosa; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Myosin-Light-Chain Kinase; NF-kappa B; Tight Junction Proteins; Transaldolase
PubMed: 36095239
DOI: 10.1021/acs.jafc.2c02909