Overcoming Oxygen Sensitivity in Faecalibacterium Prausnitzii Probiotics

Antimicrobial compounds isolated from Faecalibacterium prausnitzii supernatants, comprising heat-stable secreted compounds with molecular weights less than 10 kDa, for inhibiting bacterial growth, preventing bacterial infection, and treating diseases such as irritable bowel disease, Crohn's disease, and ulcerative colitis.

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Dry, shelf-stable compositions of live microorganisms, such as bacteria and yeast, that maintain viability and can be used for therapeutic, agricultural, and bioproduction applications. The compositions comprise microorganisms combined with specific stabilizing excipients that protect against environmental stress and degradation, enabling long-term storage and transportation without refrigeration.

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A bacterial culture medium for culturing oxygen-sensitive bacteria, such as Faecalibacterium prausnitzii, that enables anaerobic growth without the need for specialized equipment. The medium comprises yeast extract, pantothenic acid, and other nutrients, and is prepared by a process involving degassing and sterilization. The medium allows for the production of probiotics that meet strict dietary requirements, particularly for human food applications.

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Faecalibacterium prausnitzii (F. prausnitzii) exhibits a variety of biological functions that make it suitable for use as a next-generation probiotic. However, its high sensitivity to oxygen and digestive fluids currently limits its application. Riboflavin is known to support the growth of F. prausnitzii in oxygen environments, but it is important that it is in close proximity to the probiotics. Layer-by-layer assembly can be used to form protective coatings around probiotics, which can protect them from adverse environmental conditions. Moreover, riboflavin can be conjugated to these coatings, thereby increasing its efficacy by bringing it close to probiotic surfaces. In this study, we therefore evaluated the potential of electrostatic layer-by-layer assembly to protect F. prausnitzii by coating them with riboflavin-alginate and glycol-chitosan layers. Initially, we showed that riboflavin could be successfully conjugated to alginate, with a grafting ratio of around 4.35%. Then, the layer-by-layer method was used to coat F. prausnitzii using cationic glycol chitosan and anionic ribof... Read More

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Faecalibacterium prausnitzii (F. prausnitzii) has been recognized for its various intestinal and extraintestinal benefits to human. And reduction of F. prausnitzii has been linked to an increased risk of intestinal fibrosis in patients of Crohn's disease (CD). In this study, oral administration of either live F. prausnitzii or its extracellular vesicles (FEVs) can markedly mitigate the severity of fibrosis in mice induced by repetitive administration of DSS. In vitro experiment revealed that FEVs were capable of directing the polarization of peripheral blood mononuclear cells (PBMCs) towards an M2b macrophage phenotype, which has been associated with anti-fibrotic activities. This effect of FEV was found to be stable under various conditions that promote the development of pro-fibrotic M1/M2a/M2c macrophages. Proteomics and RNA sequencing were performed to uncover the molecular modulation of macrophages by FEVs. Notably, we found that FEVs reprogramed every metabolism of macrophages by damaging the mitochondria, and inhibited oxidative phosphorylation and glycolysis. Moreover, FEV-tr... Read More

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Sulfasalazine is a prodrug known to be effective for the treatment of inflammatory bowel disease (IBD)-associated peripheral spondyloarthritis (pSpA), but the mechanistic role for the gut microbiome in regulating its clinical efficacy is not well understood. Here, treatment of 22 IBD-pSpA subjects with sulfasalazine identifies clinical responders with a gut microbiome enriched in Faecalibacterium prausnitzii and the capacity for butyrate production. Sulfapyridine promotes butyrate production and transcription of the butyrate synthesis gene but in F. prausnitzii in vitro, which is suppressed by excess folate. Sulfasalazine therapy enhances fecal butyrate production and limits colitis in wild-type and gnotobiotic mice colonized with responder, but not non-responder, microbiomes. F. prausnitzii is sufficient to restore sulfasalazine protection from colitis in gnotobiotic mice colonized with non-responder microbiomes. These findings reveal a mechanistic link between the efficacy of sulfasalazine therapy and the gut microbiome with the potential to guide diagnostic and therapeutic approac... Read More

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Food additives have been linked to the pro-inflammatory microbial dysbiosis associated with Crohn's disease (CD) but the underlying ecological dynamics are unknown. Here, we examine how selection of food additives affects the growth of multiple strains of a key beneficial bacterium (Faecalibacterium prausnitzii), axenic clinical isolates of proinflammatory bacteria from CD patients (Proteus, Morganella, and Klebsiella spp.), and the consortia of mucosa-associated microbiota recovered from multiple Crohn's disease patients. Bacterial growth of the axenic isolates was evaluated using a habitat-simulating medium supplemented with either sodium sulfite, aluminum silicate, carrageenan, carboxymethylcellulose, polysorbate 80, saccharin, sucralose, or aspartame, intended to approximate concentrations found in food. The microbial consortia recovered from post-operative CD patient mucosal biopsy samples were challenged with either carboxymethylcellulose and/or polysorbate 80, and the bacterial communities compared to unchallenged consortia by 16S rRNA gene amplicon profiling. Growth of all F.... Read More

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A dietary fiber preparation containing 2′-fucosyllactose (2′-FL) and optionally other oligosaccharides, such as galacto-oligosaccharides, fructo-oligosaccharides, polydextrose, resistant starch, and human milk oligosaccharides, for increasing the abundance of Faecalibacterium prausnitzii in the gastrointestinal tract of human subjects. The preparation is particularly effective in non-infants, especially adults and elderly, and can be used to prevent, treat, or relieve symptoms of COVID-19, inflammatory bowel conditions, diabetes, anxiety, and allergies.

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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 t... Read More

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Obligate anaerobic bacteria in genus Faecalibacterium are among the most dominant taxa in the colon of healthy individuals and contribute to intestinal homeostasis. A decline in the abundance of this genus is associated with the occurrence of various gastrointestinal disorders, including inflammatory bowel diseases. In the colon, these diseases are accompanied by an imbalance between the generation and elimination of reactive oxygen species (ROS), and oxidative stress is closely linked to disruptions in anaerobiosis. In this work, we explored the impact of oxidative stress on several strains of faecalibacteria. An in silico analysis of complete genomes of faecalibacteria revealed the presence of genes encoding O2- and/or ROS-detoxifying enzymes, including flavodiiron proteins, rubrerythrins, reverse rubrerythrins, superoxide reductases, and alkyl peroxidase. However, the presence and the number of these detoxification systems varied greatly among faecalibacteria. These results were confirmed by O2 stress survival tests, in which we found that strains differed widely in their sensitiv... Read More

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A method for selectively enhancing the growth of beneficial anaerobic butyrate-producing bacteria, such as Faecaliumbacterium prausnitzii, in the gastrointestinal tract of an animal, comprising administering a combination of riboflavin and vitamin C in a specific ratio. The method is particularly useful for treating inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, by promoting the growth of F. prausnitzii, which has anti-inflammatory properties.

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A culture medium composition for Picalibacterium prosnich (Faecalibacterium prausnitzii) that enables high-density cultivation of this butyrate-producing bacterium. The medium comprises vegetable peptone, yeast extract, phosphate compound, carbonate compound, cyanocobalamin, L-cysteine, and ammonium acetate, with maltose as the primary carbon source. The composition supports growth of P. prosnich to high cell densities (up to 10^11 CFU/mL) and maintains optimal pH and morphology.

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Faecalibacterium prausnitzii (F. prausnitzii) is a bacterial taxon in the human gut with anti-inflammatory properties, and this may contribute to the beneficial effects of healthy eating habits. However, little is known about the nutrients that enhance the growth of F. prausnitzii other than simple sugars and fibers. Here, we combined dietary and microbiome data from the American Gut Project (AGP) to identify nutrients that may be linked to the relative abundance of F. prausnitzii. Using a machine learning approach in combination with univariate analyses, we identified that sugar alcohols, carbocyclic sugar, and vitamins may contribute to F. prausnitzii growth. We next explored the effects of these nutrients on the growth of two F. prausnitzii strains in vitro and observed robust and strain-dependent growth patterns on sorbitol and inositol, respectively. In the context of a complex community using in vitro fermentation, neither inositol alone nor in combinations with vitamin B exerted a significant growth-promoting effect on F. prausnitzii, partly due to high variability among the f... Read More

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Abstract Several gut microbial species within the Faecalibacterium genus have emerged as promising nextgeneration probiotics (NGP) due to their multifunctional protective effects against gastrointestinal and systemic disorders. To enable clinical studies and further applications, improved methods for cultivating Faecalibacterium must be developed in compliance with current Good Manufacturing Practice regulations, which is complicated by its oxygen sensitivity and complex nutritional requirements. Different yeastbased nutrients (YBNs), including yeast extracts (YEs) and yeast peptones (YPs), are ubiquitously used when cultivating microbes to supply a broad range of macro and micronutrients. In this study, we evaluated six experimental YBNs, namely three YEs, two YPs and a yeast cell wall product (YCW), and eight Bvitamins in the cultivation of Faecalibacterium duncaniae A2165, former Faecalibacterium prausnitzii , using growth assays in microtitre plates, doseeffect studies in Hungate tube fermentations and fully controlled bioreactor experiments. We demonstrated that YEs promot... Read More

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Introduction The commensal bacterium Faecalibacterium prausnitzii is a prominent member of the microbiome of animals and humans, and it plays an important role in several physiological processes. Numerous studies have correlated the reduction of F. prausnitzii abundance with many disease states, including irritable bowel syndrome, Crohns disease, obesity, asthma, major depressive disorder, and metabolic diseases in humans. Studies have also correlated F. prausnitzii with diseases in humans involved in altered glucose metabolism, including diabetes. Research design and methods The aim of this study was to investigate the effects of compositions derived from three strains of F. prausnitzii (coined FPZ) on glucose metabolism in diet-induced obese male C57BL/6J prediabetic and type 2 diabetic mice. The primary endpoints of these studies were measuring changes in fasting blood glucose, glucose tolerance (as measured by a glucose tolerance test), and percent hemoglobin A1c (HbA1c) with longer term treatment. Two placebo-controlled trials were carried out using both live cell FPZ and kille... Read More

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Objectives: Bacterial strains which occur differentially between CF and non-CF controls are linked to inflammatory and malignancy processes. Akkermansia muciniphila and Faecalibacterium prausnitzii have demonstrated anti-inflammatory effects and are consistently more abundant in healthy children but reduced in children with CF. Our primary objective was to quantify the inflammatory response to individual and combinations of species with known negative associations in CF, utilising patient-specific intestinal organoid models. Our secondary objective, was to evaluate if A. muciniphila and/or F. prausnitzii could improve inflammatory responses, demonstrating potential as CF-specific probiotics.

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Probiotics have been reported to exhibit various potential health and nutritional benefits. However, the efficient delivery of these probiotics to the intestine for the health benefit of the host is of much interest. Microencapsulation came up as an efficient technique to protect probiotics during gastrointestinal (GI) transit. There are many studies and reviews related to microencapsulated probiotics, but no review has been published on the microencapsulation of anaerobic probiotics especially the obligate anaerobic probiotics Bifidobacterium genus. This review article aims to summarize the microencapsulation of obligate anaerobe Bifidobacterium and seek out the optimal encapsulating methods for strictly anaerobic microbes-next-generation probiotics. The studies related to the microencapsulation of strictly anaerobic bacteria especially Bifidobacterium, Akkermansia muciniphila and Faecalibacterium prausnitzii published in the last 5 years have been reviewed. This review summarizes the encapsulants, techniques for microencapsulation, the viability of probiotics during storage and the... Read More

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Aims: We performed a randomized, placebo-controlled trial, RIBOGUT, to study the effect of 2 weeks supplementation with either 50 or 100 mg/d of riboflavin on (i) Faecalibacterium prausnitzii abundance, (ii) gut microbiota composition, (iii) short-chain fatty acid (SCFA) profiles, and (iv) the satiety and gut hormones. Results: Neither dose of riboflavin, analyzed separately, impacted the abundance of F. prausnitzii, and only minor differences in SCFA concentrations were observed. However, combining the results of the 50 and 100 mg/d groups showed a significant increase in butyrate production. While the gut bacterial diversity was not affected by riboflavin supplementation, the complexity and stability of the bacterial network were enhanced. Oral glucose tolerance tests showed a trend of increased plasma insulin concentration and GLP-1 after 100 mg/d supplementation. Innovation: Dietary supplements, such as vitamins, promote health by either directly targeting host physiology or indirectly via gut microbiota modulation. Here, we show for the first time that riboflavin intervention ch... Read More

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Faecalibacterium prausnitzii is one of the most abundant commensals of gut microbiota that is not commonly administered as a probiotic supplement. Being one of the gut's major butyrate-producing bacteria, its clinical significance and uses are on the rise and it has been shown to have anti-inflammatory and gut microbiota-modulating properties in the treatment of inflammatory bowel illness, Crohn's disease, and colorectal cancer. Colorectal cancer (CRC) is a silent killer disease that has become one of the leading causes of cancer-related death worldwide. This study aimed to evaluate the anti-tumorigenic and antiproliferative role of F. prausnitzii as well as to study its effects on the diversity of gut microbiota in rats. Findings showed that F. prausnitzii probiotic significantly reduced the colonic aberrant crypt foci frequency and formation in Azoxymethane (AOM)-induced CRC in rats. In addition, the administration of F. prausnitzii lowered the lipid peroxidation levels in the colon tissues. For in vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, the... Read More

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The human intestinal system is a complex of various anaerobes including extremely oxygen-sensitive (EOS) bacteria, some of which have been credited with significant health benefits. Among these, Faecalibacterium prausnitzii, which is one of the most abundant anaerobic bacterial strains in the human intestinal tract, has been proved to be a promising probiotic for the treatment of inflammatory bowel diseases. However, because of its extremely sensitive nature, there are many difficulties when passing through the harsh environment of the gastrointestinal tract. Hence, in this study, a comprehensive physicochemical characterization was performed for the use of polysaccharides from several origins (hydroxypropyl methyl cellulose, methyl cellulose, hydroxypropyl cellulose, chitosan, low-methoxylated pectin, kappa-carrageenan, sodium alginate and pullulan) as encapsulating agents to protect and deliver this bacterium. First, the apparent viscosity and surface tension of the polymer solutions were tested. Then, the mechanical properties, water vapor and oxygen barrier properties of these bi... Read More

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