Faecalibaterium prausnitzii strain EXL01 boosts efficacy of immune checkpoint inhibitors.

Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of Faecalibacterium prausnitzii have been associated with a positive response to ICI in multiple cancer types. Here, based on fecal shotgun metagenomics data, we show in two independent cohorts of patients with non-small cell lung cancer and advanced melanoma that a high level of F. prausnitzii at baseline is positively associated with a better clinical response to ICI. In MCA205 tumor-bearing mice, administration of F. prausnitzii strain EXL01, already in clinical development for Inflammatory Bowel Disease, restores the anti-tumor response to ICI in the context of antibiotic-induced microbiota perturbation at clinical and tumor transcriptomics level. In vitro, EXL01 strain enhances T cell activation in the presence of ICI. Interestingly, oral administration of EXL01 strain did not induce any change in fecal microbiota diversity or composition, suggesting a direct effect on immune cells in the small intestine. F. prausnitzii strain EXL01 will be evaluated as an adjuvant to ICI in multiple cancers in the near future.

Synergy and oxygen adaptation for development of next-generation probiotics.

The human gut microbiota has gained interest as an environmental factor that may contribute to health or disease1. The development of next-generation probiotics is a promising strategy to modulate the gut microbiota and improve human health; however, several key candidate next-generation probiotics are strictly anaerobic2 and may require synergy with other bacteria for optimal growth. Faecalibacterium prausnitzii is a highly prevalent and abundant human gut bacterium associated with human health, but it has not yet been developed into probiotic formulations2. Here we describe the co-isolation of F. prausnitzii and Desulfovibrio piger, a sulfate-reducing bacterium, and their cross-feeding for growth and butyrate production. To produce a next-generation probiotic formulation, we adapted F. prausnitzii to tolerate oxygen exposure, and, in proof-of-concept studies, we demonstrate that the symbiotic product is tolerated by mice and humans (ClinicalTrials.gov identifier: NCT03728868 ) and is detected in the human gut in a subset of study participants. Our study describes a technology for the production of next-generation probiotics based on the adaptation of strictly anaerobic bacteria to tolerate oxygen exposures without a reduction in potential beneficial properties. Our technology may be used for the development of other strictly anaerobic strains as next-generation probiotics.

Potent In Vitro Activity of Citrus aurantium Essential Oil and Vitis vinifera Hydrolate Against Gut Yeast Isolates from Irritable Bowel Syndrome Patients-The Right Mix for Potential Therapeutic Use.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional disorder without any pathological alteration, in which the alterations of the Candida/Saccharomyces ratio of the gut microbiota, the balance of pro and anti-inflammatory cytokines and the brain-gut-microbiome axis are important for the development and progression of IBS. The aim of the study was to identify natural products, including essential oils or hydrolates, which were contextually harmless for the gut beneficial strains (e.g. Saccharomyces spp.) but inhibitory for the pathogenic ones (Candida spp.). METHODS: The effectiveness of 6 essential oils and 2 hydrolates was evaluated using microbiological tests, carried out on 50 clinical isolates (Candida, Saccharomyces and Galattomyces species) and 9 probiotic strains (Saccharomyces cerevisiae, Lactobacillus species, Akkermansia muciniphila and Faecalibacterium prausnitzii) and immunological and antioxidant assays. RESULTS: The study led to a mixture based on a 1/100 ratio of Citrus aurantium var. amara essential oil / Vitis vinifera cv Italia hydrolate able to contextually reduce, in a concentration-dependent manner, the ability of Candida species to form hyphal filaments and have an interesting immunomodulatory and anti-oxidant action. This mixture can potentially be useful in the IBS treatment promoting the restoration of the intestinal microbial and immunological balance.

Dietary Factors and Modulation of Bacteria Strains of Akkermansia muciniphila and Faecalibacterium prausnitzii: A Systematic Review.

Akkermansia muciniphila and Faecalibacterium prausnitzii are highly abundant human gut microbes in healthy individuals, and reduced levels are associated with inflammation and alterations of metabolic processes involved in the development of type 2 diabetes. Dietary factors can influence the abundance of A. muciniphila and F. prausnitzii, but the evidence is not clear. We systematically searched PubMed and Embase to identify clinical trials investigating any dietary intervention in relation to A. muciniphila and F. prausnitzii. Overall, 29 unique trials were included, of which five examined A. muciniphila, 19 examined F. prausnitzii, and six examined both, in a total of 1444 participants. A caloric restriction diet and supplementation with pomegranate extract, resveratrol, polydextrose, yeast fermentate, sodium butyrate, and inulin increased the abundance of A. muciniphila, while a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols decreased the abundance of A. muciniphila. For F. prausnitzii, the main studied intervention was prebiotics (e.g. fructo-oligosaccharides, inulin type fructans, raffinose); seven studies reported an increase after prebiotic intervention, while two studies reported a decrease, and four studies reported no difference. Current evidence suggests that some dietary factors may influence the abundance of A. muciniphila and F. prausnitzii. However, more research is needed to support these microflora strains as targets of microbiome shifts with dietary intervention and their use as medical nutrition therapy in prevention and management of chronic disease.

Chang-wei-qing, a Chinese herbal formula, ameliorates colitis-associated tumour development via inhibiting NF-κB and STAT3 signalling pathway.

CONTEXT: Chang-wei-qing (CWQ) is a Chinese herbal recipe with clinical efficacy. However, the molecular mechanism underlying its recognized therapeutic benefits against colorectal cancer is still elusive. OBJECTIVE: To investigate the potential beneficial effects of CWQ in drug-induced colitis-associated cancer (CAC) model and its mechanistic involvements in this disease. MATERIALS AND METHODS: Colitis-associated cancer model was induced by azoxymethane (AOM) and dextran sulphate sodium (DSS). CWQ was administrated by gavage. Colon length and tumour size were determined after resection. The colitis was systematically scored. The microbiota and population of Faecalibacterium prausnitzii (F. prausnitzii) Hauduroy & Duncan was analysed by quantitative polymerase chain reaction (PCR). ß-Glucuronidase, d-lactose and endotoxin were determined with commercially available kits. Pro-inflammatory cytokines were analysed in the colon tissues. Relative protein expressions were determined by Western blotting. RESULTS: High concentration CWQ significantly restored the colon length, decreased tumour number and size (1.7 ± 0.6 vs. 2.8 ± 0.4 mm, p < 0.01) and reduced colitis score (11.8 ± 2.1 vs. 18.2 ± 2.3, p < 0.01). CWQ also suppressed expansion of F. prausnitzii population (0.029 ± 0.015% vs. 0.052 ± 0.019%, p < 0.01). CWQ greatly inhibited the activity of ß-glucuronidase and leakage of d-lactose and endotoxin. Meanwhile, the pro-inflammatory cytokines were remarkably decreased in CAC mice in response to CWQ treatment. We further demonstrated that CWQ inhibited both NF-κB and STAT3 signalling. CONCLUSIONS: We for the first time demonstrated the antitumour properties of CWQ in vivo via inhibiting NF-κB and STAT3 signalling.

Laxative effect of probiotic chocolate on loperamide-induced constipation in rats.

The fecal morphology, defecation frequency, bowel function, intestinal motility, and fecal bacterial composition were evaluated to investigate the laxative effect of probiotic chocolate containing Streptococcus thermophilus MG510 and Lactobacillus plantarum LRCC5193 (LYC) on loperamide-induced constipated rats. Daily oral administration of LYC in constipated rats for two weeks was shown to significantly increase (n = 14) the defecation frequency, fecal moisture content, and relative abundance of fecal Lactobacillus and Faecalibacterium prausnitzii. Moreover, histological analysis of the distal colon of constipated rats revealed that LYC treatment can also increase the thickness of the colonic mucosa and muscle layers, and crypt of Lieberkühn. LYC also significantly increased (n = 5) the intestinal motility and modulated (n = 9) mRNA expression levels of colonic ZO-1 and Cldn-1 in the constipated rats. Altogether, these results demonstrate that probiotic chocolate has potential as a dietary adjunct for the treatment of constipation.

Selenium nanoparticles in poultry feed modify gut microbiota and increase abundance of Faecalibacterium prausnitzii.

The poultry industry aims to improve productivity while maintaining the health and welfare of flocks. Pathogen control has been achieved through biosecurity, vaccinations and the use of antibiotics. However, the emergence of antibiotic resistance, in animal and human pathogens, has prompted researchers and chicken growers alike to seek alternative approaches. The use of new and emerging approaches to combat pathogen activity including nanotechnology, in particular, silver nanoparticles (NPs), has been found to not only eradicate pathogenic bacteria but also include issues of toxicity and bioaccumulation effects. Other novel metal nanoparticles could provide this pathogen reducing property with a more tailored and biocompatible nanomaterial for the model used, something our study represents. This study investigated the benefits of nanomaterial delivery mechanisms coupled with important health constituents using selenium as a biocompatible metal to minimise toxicity properties. Selenium NPs were compared to two common forms of bulk selenium macronutrients already used in the poultry industry. An intermediate concentration of selenium nanoparticles (0.9 mg/kg) demonstrated the best performance, improving the gut health by increasing the abundance of beneficial bacteria, such as Lactobacillus and Faecalibacterium, and short-chain fatty acids (SCFAs), in particular butyric acid. SCFAs are metabolites produced by the intestinal tract and are used as an energy source for colonic cells and other important bodily functions. Selenium nanoparticles had no significant effect on live weight gain or abundance of potentially pathogenic bacteria.

Age-associated effect of kestose on Faecalibacterium prausnitzii and symptoms in the atopic dermatitis infants.

BACKGROUND: Although Faecalibacterium prausnitzii is a major bacterium in the intestine of adults, which is known to have anti-inflammatory effects, the development in infants or the response to prebiotics remains unclear. METHODS: The counts of F. prausnitzii in the feces were examined by real-time polymerase chain reaction (PCR). Fecal samples were obtained from 65 atopic dermatitis (AD) infants who participated in a randomized controlled clinical trial to investigate the therapeutic effect of kestose, the smallest fructooligosaccharide. RESULTS: Although the F. prausnitzii count was undetectable level in most 0- to 1-y-old infants, the count reached a level comparable to that in adults in 2- to 5-y-old infants. The bacterial number increased about 10-fold by oral administration of kestose every day for 12 wk in the younger infants, but not so much in the older infants. This bacterial increase was significantly correlated with an improvement in the AD symptoms in the older infants. CONCLUSION: The F. prausnitzii population in the intestine reaches a level comparable to that in adult at approximately 2 y of age. Kestose efficiently stimulates the growth of this bacterium in the intestine, which might lead to an improvement in AD symptoms in infants.