Beneficial microbes最新文献

Faecalibacterium is an essential probiotic in the human gut; changes in its abundance are associated with various disease states in many studies. However, the causal nature of such associations remains obscure. Therefore, we aimed to thoroughly investigate the causal relationships between Faecalibacterium and its related diseases. A two-sample bi-directional Mendelian randomisation analysis was conducted using publicly available genome-wide association studies summary statistics for Faecalibacterium and its related diseases. We found that Faecalibacterium was negatively correlated with the risk of ankylosing spondylitis (odds ratio [OR] = 0.526, 95% confidence interval [CI]:0.304-0.908, P = 0.021), atopic dermatitis (OR = 0.484, 95%CI: 0.261-0.898, P = 0.021) and heart failure (OR = 0.657, 95%CI: 0.467-0.924, P = 0.016), while Faecalibacterium was positively associated with autism spectrum disorder risk (OR = 2.529, 95%CI: 1.012-6.319, P = 0.047). The results of reverse Mendelian randomisation analysis showed that acute sinusitis (OR = 0.902, 95%CI: 0.839-0.970, P = 0.005) and Alzheimer's disease (OR = 0.976, 95%CI: 0.958-0.993, P = 0.008) was causally associated with lower Faecalibacterium abundance, respectively, while cirrhosis (OR = 1.154, 95%CI: 1.028-1.295, P = 0.015) and multiple myeloma (OR = 2.619 × 1012, 95%CI: 2.492-2.754 × 1024, P = 0.043) was causally associated with higher Faecalibacterium abundance. Our findings firstly showed that changes in Faecalibacterium abundance may contribute to the risk of ankylosing spondylitis, atopic dermatitis, heart failure and autism spectrum disorders, and potentially as a result of acute sinusitis, Alzheimer's disease, cirrhosis and multiple myeloma.

Probiotics can confer a beneficial effect on gastrointestinal-related symptoms and their impact on daily life. This randomised, double-blind, placebo-controlled study assessed the efficacy of a novel probiotic strain Bacillus subtilis ATCC 122264 as a probiotic on gas-related symptoms in healthy adults. One hundred healthy adults with functional bloating/distension according to the ROME IV criteria, were randomised in a 1:1 ratio to receive either 5 billion cfu of B. subtilis) or placebo daily for 8 weeks. Intestinal gas symptoms and impact on daily life were assessed weekly by the 17-item Intestinal Gas Questionnaire (IGQ) and the change from baseline was analysed by ANCOVA at 4 and 8 weeks. Post-hoc analyses were conducted on the two parts of the IGQ, scored separately. Sub-group analyses based on sex were also done on the IGQ global and dimension scores as well as the scores from the two individual parts of the IGQ. Safety was assessed by reports of adverse events. B. subtilis did not differ from placebo in the change from baseline to Weeks 4 or 8 in IGQ global score or dimension scores of bloating, flatulence, belching, bad breath, stomach rumbling and difficult gas evacuation ( P > 0.05). In females taking B. subtilis, the severity of belching and flatulence significantly decreased after 4 ( P = 0.046) and 8 weeks ( P = 0.039) respectively, compared to females taking placebo. The impact of flatulence on daily life decreased after 8 weeks in females taking B. subtilis compared to placebo ( P = 0.03). B. subtilis was safe and well tolerated over the 8-week study period. The results suggest that B. subtilis may reduce gas-related symptoms, such as bloating and flatulence, in females. Further studies are needed to confirm the sex-related effects of B. subtilis in populations with gastrointestinal symptoms. Registered at Clinicaltrials.gov: NCT06308146.

Prebiotics are becoming increasingly recognized by consumers, health care professionals and regulators as important contributors to health. Nonetheless, the development, progress, and adoption of prebiotics is hindered by loose terminology, various misconceptions about sources and types of compounds that may be classified as prebiotics, and the lack of consensus on a definition that satisfies regulators. Evolving knowledge of the microbiome and its effects on host health has generated opportunities for modulation of the microbiota that can support host health. Various types of biotics - probiotics, prebiotics, and postbiotics, are compounds that either modulate the microbiota or arise from the microbiota, affecting health locally and distally. Each of these classes of biotic compounds have distinct, yet complementary benefits. While many scientists have proposed definitions for prebiotics, and there have been attempts by selected scientists to develop a 'consensus definition', the fact remains that globally, scientists, manufacturers, and marketers have adopted different definitions to suit their own interests and purposes, leading to confusion among consumers and health care professionals. The pathway to regulatory acceptance and to reduce/eliminate confusion is a definition that puts the focus on the consumer, and the benefits that consumers can realise from consumption of prebiotics. This consumer-focused approach, supported by science, will also align with regulators and support broader regulatory approval of prebiotics as a category. In this review, we discuss the history of prebiotics, and introduce criteria and a decision tree to classify compounds as prebiotics, supported by the scientific literature to date. This includes a summary of compounds that have been clearly recognised as prebiotics. We also review the microbiota, microbiome, and the various ways in which prebiotics can beneficially affect the microbiota and health. The safety and efficacy of prebiotics is also reviewed, along with effective doses and limitations associated with prebiotic use. This includes scientific tools and methods that help to establish the function, safe use and efficacy of a prebiotic. We also identify misconceptions that can be addressed in communications to consumers and health care professionals. Manufacturing guidelines and the current regulatory status of prebiotics in various jurisdictions are also reviewed. Collectively, this review provides an in-depth overview of the role for prebiotics to support the health of consumers. This consumer-focused approach provides clear criteria for the product category, safe use, effective communication of health benefits and limitations, and a pathway towards regulatory approval.

Understanding the viability of ingested probiotics within the gastrointestinal tract is essential for evaluating their efficacy and deciphering their mechanisms of action. Detecting Bifidobacterium longum subspecies longum BB536 is particularly challenging owing to its indistinguishability from the naturally abundant B. longum species in the human gut. We aimed to address this challenge by developing a selective culture medium for B. longum BB536 and employing a propidium monoazide-quantitative polymerase chain reaction (PMA-qPCR) method to verify the survival of the probiotic after consumption. To achieve this, we designed a novel lactose-mupirocin-trimethoprim (LMT) medium that facilitates the cultivation of B. longum BB536 under anaerobic conditions at 42 °C. We screened 52 healthy adults and enrolled 39 who met the eligibility criteria. The participants were randomised into two groups, with 34 completing the protocol: 17 received commercial yogurt containing B. longum BB536 (9.30 log10 cfu/day) and 17 received a placebo. Prior to the intervention, B. longum BB536 was undetectable in all participants. However, following supplementation, LMT culturing identified viable B. longum BB536, with average counts of 6.33 ± 0.69 log10 cfu/g on day 3 and 6.16 ± 0.74 log10 cfu/g on day 17. PMA-qPCR further validated these results, showing viable cell counts of 6.09 ± 0.68 log10 cells/g wet faeces on day 3 and 6.44 ± 0.64 log10 cells/g wet faeces on day 17. While each method detected B. longum BB536 in some participants where the other did not, no participant tested negative by both methods at any time point. This complementarity between LMT culturing and PMA-qPCR ensures a comprehensive detection strategy, confirming the presence and resilience of B. longum BB536 in the gastrointestinal tract and underscoring its potential as a beneficial probiotic strain (UMIN000052110). Japan Conference of Clinical Research: registration number: BYG2B-01; University Hospital Medical Information Network: study protocol registration UMIN000052110.

Probiotics are widely used for their health promoting effects, though a lot remain to be discovered, particularly on their mechanisms of action at the molecular level. The functional genomic approach is an appropriate method to decipher how probiotics may influence human cell fate and therefore contribute to their health benefit. In the present work, we focused on Shouchella clausii (formerly named Bacillus then Alkalihalobacillus clausii), a spore-forming bacterium that is commercially available as a probiotic for the prevention and the treatment of intestinal dysbiosis and related gastrointestinal disorders, such as diarrhoea. Several studies have demonstrated that S. clausii treatment modulated inflammatory and immune responses, as well as gut barrier functions. A functional genomic strategy was implemented to decipher the mechanisms by which S. clausii exerts its probiotic effects on human intestinal epithelial cells. To do so, a large genomic DNA fragment library was constructed for each of the four strains: O/C, N/R, SIN and T. A high throughput in vitro screening in human epithelial cells was then conducted, using the reporter gene strategy, targeting the nuclear factor kappa B (NF-κB) pathway and interleukin-10 (IL-10) gene expression. After an exhaustive in vitro screening of approximately a thousand clones per library, several clones modulating the NF-κB pathway in the HT-29 reporter cell line were identified. Among clone lysates, 1.1% (O/C), 1.4% (N/R), 2.0% (SIN), and 1.2% (T) were identified as biologically active on immune reporter systems (NF-κB and IL-10 expression). After transposon mutagenesis and a new set of screening and sequencing, 23 coding sequences (CDS) were identified, including one encoding for the glutamine synthetase, associated with NF-κB modulation, and six CDS for IL-10 modulation. The functional genomic strategy that was applied to S. clausii was an original approach to identify gene candidates that may explain the mechanisms of action of probiotics. However, further work is needed to validate the identified leads.

Imbalances in the gut microbiome have emerged as an important factor in endothelial dysfunction, a significant risk factor for cardiovascular disease. Thus, interventions targeting the microbiome may prove helpful in preventing or reversing this impairment. We previously reported that spore-forming Bacillus subtilis DE111 improved endothelial function in a cohort of healthy, non-obese humans after a four-week intervention. Building on these promising results, the present study sought to investigate whether administering B. subtilis DE111 could reverse endothelial dysfunction in mice with diet-induced obesity. Male C57BL/6J mice were fed a Western diet (WD; n = 24) or standard diet (SD; n = 24) for ten weeks to induce endothelial dysfunction, after which half of the animals in each group (n = 12) were allocated to receive B. subtilis DE111 (hereafter, PB) formulated into the diet for an additional eight weeks. Outcomes included endothelial-dependent arterial dilation, glucose tolerance, body weight changes, microbiota profiles, and assessments of intestinal permeability and mucosal immunity markers. Furthermore, a cell culture model of gut barrier function was used to assess the effects of PB on gut barrier integrity. PB treatment significantly attenuated WD-induced mesenteric endothelial-dependent arterial dilation, independent of changes in other cardiometabolic parameters or changes in gut barrier function. In vitro trans-epithelial electrical resistance of the Caco-2 cell culture confirmed that neither PB-conditioned media nor faecal waters from B. subtilis-treated human stool resulted in gut barrier improvements, nor did they protect against inflammation-associated barrier disruptions. Unsurprisingly, microbiota analysis revealed significant differences in Shannon's alpha diversity of WD-fed animals compared to SD. These data suggest that PB consumption significantly attenuated WD diet-induced endothelial dysfunction; however, the underlying mechanisms of this protection were not determined. Improvement in endothelial function was independent of PB-mediated changes to body weight or gut barrier function. Further studies should explore B. subtilis-mediated immune responses or metabolite production as mechanisms underlying these endothelial protective effects.

Prenatal stress (PNS) has widespread effects on offspring, including aberrant immune development and behavioural deficits. The microbiome is a mediator of the dissemination of stress effects to the offspring through immunomodulation and metabolite production. Metabolites derived from the mother and their gut microbiota pass to the foetus and can affect immune and nervous development. Stress affects the abundance of such metabolites, including the tryptophan (Trp) pathway, which are involved in immune and nervous system function. We hypothesized that the PNS is associated with dysregulation of Trp metabolism. We further posited that treatment with a Trp-metaboliser Parasutterella excrementihominis would abrogate PNS-associated deleterious effects on offspring development. To test this hypothesis, pregnant mice were exposed to restraint stress and administered P. excrementihominis (Dam n = 3-9; Offspring n = 5-10). PNS increased maternal gut Trp and both maternal and offspring inflammation. P. excrementihominis treatment reduced the PNS-induced excess pool of maternal gut Trp. Some PNS effects on foetal neuroinflammation were reduced in severity due to handling effects from bacterial gavage. However, P. excrementihominis was anti-inflammatory in dam and offspring and anxiolytic in offspring of Pe-treated dams. These data illustrate that elevated Trp levels are associated PNS and its downstream deleterious offspring inflammatory and behavioural outcomes while P. excrementihominis, a Trp-metabolizer, can ameliorate these effects and improve offspring outcomes.

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. The selection criteria for probiotics include strain safety, viability, tolerance, metabolite production and/or the ability to modulate the immune system. Probiotics are commonly used in industries, such as food, agriculture, medicine, biotechnology, pharmaceuticals, and aquaculture. Recently, the medicinal applications of probiotics have gained attention and are being explored for the prevention and treatment of various diseases. One emerging area of interest is their potential role in psychological disorders. Mental illnesses, characterised by disturbances in behaviour, mood, thinking, and emotions, affect over one billion people globally. While various preventive and treatment options for mental disorders exists, each is associated with certain limitations. A new avenue being explored is the gut-brain axis, a complex bi-directional communication between the gut and the brain, that is facilitated by hormonal, neuronal, humoral, and immunological pathways. This system plays an important role in mental health. Probiotics, as a key modulator of the gut microbiome, could play a vital role in this communication. However, the underlying mechanisms remain to be explored. Probiotics may act through the production of metabolites and neuroactive substances, as well as through immunomodulation and cytokine production. Current data shows promising effects on stress, mood, and depression, presenting probiotics as a potential natural treatment option for psychological disorders. Nevertheless, major limitations in the existing research include insufficient clinical outcomes, limited sample sizes, and variable dosing. Future advancements may be achieved through stratifications based on gut microbiota, the use of next-generation probiotic strains, and the conduct of comprehensive validation studies.

Maternal separation (MS) in mice results in behavioral deficits and gut microbiota dysbiosis that all persist into adulthood. Limosilactobacillus reuteri DSM 17938 modulates gut microbiota, alters systemic metabolites, and facilitates immune regulation. To assess the effect of DSM 17938 on biochemical and behavioural stress-associated changes, newborn mice were exposed to unpredictable MS (MSU) daily from day 7 to day 20 of life, with intragastric administration of DSM 17938 or PBS as control. Body weight, brain levels of cholecystokinin (CCK), glial fibrillary acidic protein (GFAP), corticosterone, and stool microbiota were assessed at day 21. Behaviour tests including Y-maze (YMT), Tail Suspension (TST), and Open Field (OFT) were evaluated in adult mice. MSU resulted in a decrease in early postnatal growth, which improved with DSM 17938. Reduced CCK and increased corticosterone brain levels due to MSU were reversed by DSM 17938. GFAP levels increased with MSU, indicating that the decreased brain CCK was likely secondary to neuronal damage. DSM 17938 treated offspring demonstrated better cognitive function and less anxious behaviour in adult behaviour tests. DSM 17398 corrected stress related gut microbial dysbiosis. In conclusion, early life modulation of gut microbiota by DSM 17938 had beneficial effects on stress-associated physical and biochemical changes caused by MS in neonates and on subsequent adult behaviour.

The current approaches for detecting most colorectal polyps and early neoplasms lack sufficient sensitivity and specificity, potentially hindering treatment and ultimately reducing survival rates. Here, we performed a metagenomic analysis to identify microbiome markers in stool samples from patients with early-stage colorectal cancer (CRC). We compared the composition of gut microbiota between patients with CRC and healthy individuals, specifically focusing on patients with early-stage CRC, defined as those without core mutations (KRAS, BRAF) for CRC diagnosis, stable microsatellite instability, and distant metastasis. The aim of our study is to identify potential biomarkers from gut microbiota at different cancer stages in colorectal cancer (CRC) patients through 16S rRNA amplicon sequencing, thereby proposing a novel non-invasive method for the early diagnosis of CRC. Specific microbes were detected from groups divided based on the TNM criteria, with one group classified by tumour size only (named the T group) and another group with lymph node metastasis (named the TN group). Aerobic bacteria, such as Delftia, Stenotrophomonas, Sphingobacterium, Rhodococcus, Devosia, Ensifer, and Psychrobacter were predominantly detected in patients with CRC without lymph node metastasis. The diagnostic prediction was evaluated using the CatBoost algorithm; these microbes presented high diagnostic accuracy with a receiver operating characteristics-area under curve of 0.8, which was validated using qPCR. In conclusion, this study identified specific aerobic microbial groups as non-invasive biomarkers for early diagnosis in patients with CRC without genetic or environmental factors.