A higher bacterial inward BCAA transport driven by Faecalibacterium prausnitzii is associated with lower serum levels of BCAA in early adolescents.

BACKGROUND: Elevations of circulating branched-chain amino acids (BCAA) are observed in humans with obesity and metabolic comorbidities, such as insulin resistance. Although it has been described that microbial metabolism contributes to the circulating pool of these amino acids, studies are still scarce, particularly in pediatric populations. Thus, we aimed to explore whether in early adolescents, gut microbiome was associated to circulating BCAA and in this way to insulin resistance. METHODS: Shotgun sequencing was performed in DNA from fecal samples of 23 early adolescents (10-12 years old) and amino acid targeted metabolomics analysis was performed by LC-MS/MS in serum samples. By using the HUMAnN2 algorithm we explored microbiome functional profiles to identify whether bacterial metabolism contributed to serum BCAA levels and insulin resistance markers. RESULTS: We identified that abundance of genes encoding bacterial BCAA inward transporters were negatively correlated with circulating BCAA and HOMA-IR (P < 0.01). Interestingly, Faecalibacterium prausnitzii contributed to approximately ~ 70% of bacterial BCAA transporters gene count. Moreover, Faecalibacterium prausnitzii abundance was also negatively correlated with circulating BCAA (P = 0.001) and with HOMA-IR (P = 0.018), after adjusting for age, sex and body adiposity. Finally, the association between Faecalibacterium genus and BCAA levels was replicated over an extended data set (N = 124). CONCLUSIONS: We provide evidence that gut bacterial BCAA transport genes, mainly encoded by Faecalibacterium prausnitzii, are associated with lower circulating BCAA and lower insulin resistance. Based on the later, we propose that the relationship between Faecalibacterium prausnitzii and insulin resistance, could be through modulation of BCAA.

Systematic review and meta-analysis of the role of Faecalibacterium prausnitzii alteration in inflammatory bowel disease.

BACKGROUND AND AIM: We comprehensively carry out a systematic review and meta-analysis of previous studies to determine the association between intestinal Faecalibacterium prausnitzii (F. prausnitzii) and inflammatory bowel disease (IBD) in human studies. METHODS: A systematic literature search of PubMed, Embase, and the Cochrane Library database was conducted until April 1, 2020. Inclusion criteria were studies involving patients with Crohn's disease (CD) or ulcerative colitis (UC) with abundance of F. prausnitzii. The quality of the studies was assessed by the modified Newcastle-Ottawa scale. RESULTS: A total of 1669 subjects (427 CD patients, 560 UC patients, and 682 healthy controls) were enrolled from 16 studies. Both CD (standardized mean difference [SMD]: -1.36; 95% CI, -1.74 to -0.98; P < 0.00001) and UC patients (SMD: -0.81; 95% CI, -1.21 to -0.42; P < 0.0001) had a lower abundance of F. prausnitzii than the healthy controls. Compared with the IBD remission patients, the IBD active patients had lower levels of F. prausnitzii (SMD: -0.56; 95% CI, -0.91 to -0.21; P = 0.002). In the subgroup analyses, the abundance of F. prausnitzii was reduced in both active CD patients (SMD: -0.78; 95% CI, -1.51 to -0.04; P = 0.04) and active UC patients (SMD:-0.44; 95%CI, -0.81 to -0.07; P = 0.02) when compared with the patients with CD or UC in remission, respectively. CONCLUSION: A negative association between abundance of F. prausnitzii and IBD activity is observed, but a cut-off level of F. prausnitzii to diagnose and/or to start treating IBD is not determined.

Both living and dead Faecalibacterium prausnitzii alleviate house dust mite-induced allergic asthma through the modulation of gut microbiota and short-chain fatty acid production.

BACKGROUND: Asthma is increasingly prevalent worldwide, and novel strategies to prevent or treat this disease are needed. Probiotic intervention has recently been reported to be effective for asthma prevention. Here, we explored the effects of Faecalibacterium prausnitzii on the development of allergic airway inflammation in a murine model of house dust mite (HDM)-induced allergic asthma. RESULTS: Supplementation with living and dead F. prausnitzii blocked eosinophil, neutrophil, lymphocyte and macrophage influx and alleviated the pathological changes. Moreover, both living and dead F. prausnitzii administration decreased the levels of interleukin (IL)-4, IL-5, IL-13 and immunoglobulin G1, elevated regulatory T cell (Tregs) ratio, improved microbial dysbiosis and enhanced short-chain fatty acid (SCFA) production. Network correlation analysis revealed that the immune indicators were strongly associated with SCFA production. Based on the linear discriminant analysis effect size, Turicibacter was found to be the core genus related to HDM-induced asthma. Living F. prausnitzii treatment enriched Faecalibaculum, Dubosiella and Streptococcus, while dead F. prausnitzii treatment increased Muribaculaceae and Parabacteroides. Interestingly, both living and dead F. prausnitzii administration enriched Lachnoclostridium and normalized the pathways involving carbohydrate and lipid metabolism, which might be related to SCFA production. CONCLUSION: Faecalibacterium prausnitzii exerts an anti-asthmatic effect partly by gut microbiota modulation and SCFA production, suggesting its potential as a probiotic agent for allergic asthma prevention. © 2021 Society of Chemical Industry.

Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer.

BACKGROUND: The aim was to evaluate the changes of 16S rDNA sequencing and LC-MS metabolomics in breast cancer and explore the growth inhibition of breast cancer cells by Faecalibacterium prausnitzii. RESULTS: Total 49 significantly different flora and 26 different metabolites were screened between two groups, and the correlation was calculated. Relative abudance of Firmicutes and Bacteroidetes were decreased, while relative abundance of verrucomicrobla, proteobacteria and actinobacteria was increased in breast cancer group. Differentially expressed metabolites were mainly enriched in pathways such as linoleic acid metabolism, retrograde endocannabinoid signaling, biosynthesis of unsaturated fatty acids, choline metabolism in cancer and arachidonic acid metabolism. Lipid upregulation was found in breast cancer patients, especially phosphorocholine. The abundance of Faecalibacterium was reduced in breast cancer patients, which was negatively correlated with various phosphorylcholines. Moreover, Faecalibacterium prausnitzii, the most well-known species in Faecalibacterium genus, could inhibit the secretion of interleukin-6 (IL-6) and the phosphorylation of Janus kinases 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) in breast cancer cells. Faecalibacterium prausnitzii also suppressed the proliferation and invasion and promoted the apoptosis of breast cancer cells, while these effects disappeared after adding recombinant human IL-6. CONCLUSIONS: Flora-metabolites combined with the flora-bacteria (such as Faecalibacterium combined with phosphorocholine) might a new detection method for breast cancer. Faecalibacterium may be helpful for prevention of breast cancer. Faecalibacterium prausnitzii suppresses the growth of breast cancer cells through inhibition of IL-6/STAT3 pathway.

Reduced Akkermansia muciniphila and Faecalibacterium prausnitzii levels in the gut microbiota of children with allergic asthma.

INTRODUCTION AND OBJECTIVES: The amounts of Akkermansia muciniphila and Faecalibacterium prausnitzii in gut microbiota are reduced in patients with allergic diseases compared to healthy controls. We aimed to quantify levels of A. muciniphila and F. prausnitzii amounts using real-time quantitative PCR (qPCR) in the gut microbiota of children with allergic asthma and in healthy controls. MATERIALS AND METHODS: In total, 92 children between the ages of three and eight who were diagnosed with asthma and 88 healthy children were included in the study and bacterial DNA was isolated from the stool samples using the stool DNA isolation Kit. qPCR assays were studied with the microbial DNA qPCR Kit for A. muciniphila and microbial DNA qPCR Kit for F. prausnitzii. RESULTS: Both bacterial species showed a reduction in the patient group compared to healthy controls. A. muciniphila and F. prausnitzii were found to be 5.45±0.004, 6.74±0.01 and 5.71±0.002, 7.28±0.009 in the stool samples of the asthma and healthy control groups, respectively. CONCLUSIONS: F. prausnitzii and A. muciniphila may have induced anti-inflammatory cytokine IL-10 and prevented the secretion of pro-inflammatory cytokines like IL-12. These findings suggest that A. muciniphila and F. prausnitzii may suppress inflammation through its secreted metabolites.

Causal Relationship between Diet-Induced Gut Microbiota Changes and Diabetes: A Novel Strategy to Transplant Faecalibacterium prausnitzii in Preventing Diabetes.

The incidence of metabolic disorders, including diabetes, has elevated exponentially during the last decades and enhanced the risk of a variety of complications, such as diabetes and cardiovascular diseases. In the present review, we have highlighted the new insights on the complex relationships between diet-induced modulation of gut microbiota and metabolic disorders, including diabetes. Literature from various library databases and electronic searches (ScienceDirect, PubMed, and Google Scholar) were randomly collected. There exists a complex relationship between diet and gut microbiota, which alters the energy balance, health impacts, and autoimmunity, further causes inflammation and metabolic dysfunction, including diabetes. Faecalibacterium prausnitzii is a butyrate-producing bacterium, which plays a vital role in diabetes. Transplantation of F. prausnitzii has been used as an intervention strategy to treat dysbiosis of the gut's microbial community that is linked to the inflammation, which precedes autoimmune disease and diabetes. The review focuses on literature that highlights the benefits of the microbiota especially, the abundant of F. prausnitzii in protecting the gut microbiota pattern and its therapeutic potential against inflammation and diabetes.

An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii.

Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner. Here, we established a gut epithelium-microbe-immune (GuMI) microphysiological system to maintain the long-term continuous co-culture of Faecalibacterium prausnitzii/Faecalibacterium duncaniae with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), and CD4+ naive T cells circulating underneath the colonic epithelium. In GuMI-APC condition, multiplex cytokine assays suggested that APCs contribute to the elevated level of cytokines and chemokines secreted into both apical and basolateral compartments compared to GuMI condition that lacks APC. In GuMI-APC with F. prausnitzii (GuMI-APC-FP), F. prausnitzii increased the transcription of pro-inflammatory genes such as toll-like receptor 1 (TLR1) and interferon alpha 1 (IFNA1) in the colonic epithelium, without a significant effect on cytokine secretion, compared to the GuMI-APC without bacteria (GuMI-APC-NB). In contrast, in the presence of CD4+ naive T cells (GuMI-APCT-FP), TLR1, IFNA1, and IDO1 transcription levels decreased with a simultaneous increase in F. prausnitzii-induced secretion of pro-inflammatory cytokines (e.g., IL8) compared to GuMI-APC-FP that lacks T cells. These results highlight the contribution of individual innate immune cells in regulating the immune response triggered by the gut commensal F. prausnitzii. The integration of defined populations of immune cells in the gut microphysiological system demonstrated the usefulness of GuMI physiomimetic platform to study microbe-epithelial-immune interactions in healthy and disease conditions.

The alga Euglena gracilis stimulates Faecalibacterium in the gut and contributes to increased defecation.

The alga Euglena gracilis (E. gracilis) has recently gained attention as a health food, but its effects on human gut microbiota remain unknown. This study aimed to determine the effect of E. gracilis on gut microbiota and defecation due to modulation of microbiota composition in vitro and in vivo. The in vitro model simulating human colonic microbiota revealed that E. gracilis addition stimulated the growth of commensal Faecalibacterium. Further, E. gracilis addition enhanced butyrate production by Faecalibacterium prausnitzii. Paramylon, an insoluble dietary fibre that accumulates in E. gracilis and is the main component of E. gracilis, did not stimulate Faecalibacterium growth in vitro. Daily ingestion of 2 g of E. gracilis for 30 days increased bowel movement frequency as well as stool volume in 28 human participants. Collectively, these findings indicate that E. gracilis components other than paramylon, stimulate the growth of Faecalibacterium to improve digestive health as well as promote defecation by increasing butyrate production.

Identification of Faecalibacterium prausnitzii strains for gut microbiome-based intervention in Alzheimer's-type dementia.

Evidence linking the gut-brain axis to Alzheimer's disease (AD) is accumulating, but the characteristics of causally important microbes are poorly understood. We perform a fecal microbiome analysis in healthy subjects and those with mild cognitive impairment (MCI) and AD. We find that Faecalibacterium prausnitzii (F. prausnitzii) correlates with cognitive scores and decreases in the MCI group compared with the healthy group. Two isolated strains from the healthy group, live Fp360 and pasteurized Fp14, improve cognitive impairment in an AD mouse model. Whole-genome comparison of isolated strains reveals specific orthologs that are found only in the effective strains and are more abundant in the healthy group compared with the MCI group. Metabolome and RNA sequencing analyses of mouse brains provides mechanistic insights into the relationship between the efficacy of pasteurized Fp14, oxidative stress, and mitochondrial function. We conclude that F. prausnitzii strains with these specific orthologs are candidates for gut microbiome-based intervention in Alzheimer's-type dementia.

Vitamin Biosynthesis by Human Gut Butyrate-Producing Bacteria and Cross-Feeding in Synthetic Microbial Communities.

We investigated the requirement of 15 human butyrate-producing gut bacterial strains for eight B vitamins and the proteinogenic amino acids by a combination of genome sequence analysis and in vitro growth experiments. The Ruminococcaceae species Faecalibacterium prausnitzii and Subdoligranulum variabile were auxotrophic for most of the vitamins and the amino acid tryptophan. Within the Lachnospiraceae, most species were prototrophic for all amino acids and several vitamins, but biotin auxotrophy was widespread. In addition, most of the strains belonging to Eubacterium rectale and Roseburia spp., but few of the other Lachnospiraceae strains, were auxotrophic for thiamine and folate. Synthetic coculture experiments of five thiamine or folate auxotrophic strains with different prototrophic bacteria in the absence and presence of different vitamin concentrations were carried out. This demonstrated that cross-feeding between bacteria does take place and revealed differences in cross-feeding efficiency between prototrophic strains. Vitamin-independent growth stimulation in coculture compared to monococulture was also observed, in particular for F. prausnitzii A2-165, suggesting that it benefits from the provision of other growth factors from community members. The presence of multiple vitamin auxotrophies in the most abundant butyrate-producing Firmicutes species found in the healthy human colon indicates that these bacteria depend upon vitamins supplied from the diet or via cross-feeding from other members of the microbial community.IMPORTANCE Microbes in the intestinal tract have a strong influence on human health. Their fermentation of dietary nondigestible carbohydrates leads to the formation of health-promoting short-chain fatty acids, including butyrate, which is the main fuel for the colonic wall and has anticarcinogenic and anti-inflammatory properties. A good understanding of the growth requirements of butyrate-producing bacteria is important for the development of efficient strategies to promote these microbes in the gut, especially in cases where their abundance is altered. The demonstration of the inability of several dominant butyrate producers to grow in the absence of certain vitamins confirms the results of previous in silico analyses. Furthermore, establishing that strains prototrophic for thiamine or folate (butyrate producers and non-butyrate producers) were able to stimulate growth and affect the composition of auxotrophic synthetic communities suggests that the provision of prototrophic bacteria that are efficient cross feeders may stimulate butyrate-producing bacteria under certain in vivo conditions.

Gut microbiome associated with APC gene mutation in patients with intestinal adenomatous polyps.

Background: The 'adenoma-carcinoma sequence' is a well-recognized model of colorectal cancer (CRC) development. However, the interaction between gut microbiota and genetic variation in the initiation of CRC is not clear. Our study attempts to demonstrate the relationship between gut microbiota and host genetics in patients with intestinal adenomatous polyps. Method: The entire exon region of the APC gene was sequenced in 35 patients with pathologically diagnosed adenomatous polyps. Patients with highly pathogenic APC mutation were classified as the case group, while the others were classified as the control group. The patients'stool and serum samples were respectively collected for metagenomics and metabolomics measurements. Results: In the analysis of gut microbiome, there were three most important species, in which Fusobacterium_mortiferum was significantly increased while Faecalibacterium_prausnitzii and Bifidobacterium_pseudocatenulatum were significantly decreased in the case group. The significantly low abundance of the Photosynthesis pathway in patients with APC mutation was due to the low abundance of species Faecalibacterium_prausnitzii and Bifidobacterium_pseudocatenulatum. Moreover, there were two clusters of KEGG pathways correlated with two clusters of species characterized by Faecalibacterium_prausnitzii and Fusobacterium_mortiferum. As to serum metabolomics, the abundance of (R)-3-Hydroxybutyric acid and 2-Hydroxyphenethylamine were significantly higher in patients with APC mutation, while the abundance of 1-Aminocyclopropanecarboxylic acid,7-Ketocholesterol, DL-lactate, and L-Pyroglutamic acid were significantly higher in controlgroup. After analyzing the metabolome and microbiome data by sparCCmethod, we found that there was a significantly negative correlation between the abundance of Faecalibacterium_prausnitzii and Fusobacterium_mortiferum, and a significantly positive correlation between Faecalibacterium_prausnitzii abundance and the steroid hormone Hydrocortisone (Cortisol) in serum. Conclusions: Host's APC mutation was closely related to the changes of gut microbiota and serum metabolites, and some species of gut microbiome like Faecalibacterium_prausnitzii and Fusobacterium_mortiferum might have the potential to predict the development of CRC from intestinal adenomatous polyps.

Butyrate mediates anti-inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through Dact3.

The commensal bacterium Faecalibacterium prausnitzii plays a key role in inflammatory bowel disease (IBD) pathogenesis and serves as a general health biomarker in humans. However, the host molecular mechanisms that underlie its anti-inflammatory effects remain unknown. In this study we performed a transcriptomic approach on human intestinal epithelial cells (HT-29) stimulated with TNF-α and exposed to F. prausnitzii culture supernatant (SN) in order to determine the impact of this commensal bacterium on intestinal epithelial cells. Moreover, modulation of the most upregulated gene after F. prausnitzii SN contact was validated both in vitro and in vivo. Our results showed that F. prausnitzii SN upregulates the expression of Dact3, a gene linked to the Wnt/JNK pathway. Interestingly, when we silenced Dact3 expression, the effect of F. prausnitzii SN was lost. Butyrate was identified as the F. prausnitzii effector responsible for Dact3 modulation. Dact3 upregulation was also validated in vivo in both healthy and inflamed mice treated with either F. prausnitzii SN or the live bacteria, respectively. Finally, we demonstrated by colon transcriptomics that gut microbiota directly influences Dact3 expression. This study provides new clues about the host molecular mechanisms involved in the anti-inflammatory effects of the beneficial commensal bacterium F. prausnitzii.

Faecalibacterium prausnitzii (ATCC 27766) has preventive and therapeutic effects on chronic unpredictable mild stress-induced depression-like and anxiety-like behavior in rats.

The realization that the microbiota-gut-brain axis plays a critical role in health and disease,including neuropsychiatric disorders, is rapidly advancing．An abundance of preclinical studies have shown that psychobiotics acting via the brain-gut-axis can affect brain development, function and behavior. Here we tested whether potential psychobiotics Faecalibacterium prausnitzii (ATCC 27766) has anxiolytic and antidepressant-like effects and reverse the impact of chronic unpredictable mild stress (CUMS) in rats. The experiment was divided into two phases, the first stage was CUMS procedure period and the second stage was convalescence period. SD male rats were administered Faecalibacterium prausnitzii for 4 weeks prior to testing during each period. Behavior, growth status, SCFAs produced, plasma cytokine, endocrinology and bone mineral density (BMD) were assessed. Our findings indicate that the administration of F. prausnitzii had preventive and therapeutic effects on CUMS-induced depression-like and anxiety-like behavior. In addition, F. prausnitzii administration could significantly prevent the reduction of the whole-body, femur and tibia BMD during the recovery phase. Moreover, the growth status of rats fed the F. prausnitzii was better than the rats by CUMS. And F. prausnitzii administration led to higher levels of SCFAs in the cecum and higher levels of cytokines interleukin-10 (IL-10) in the plasma, prevented the effects on corticosterone, C-reaction protein and cytokines interleukin-6 (IL-6) release induced by CUMS, changes that were associated with the effects seen on behavior. These results provide further evidence that gut microflora play a role in anxiety and depression. Subject to the confirmation of these results, probiotics might offer a useful novel therapeutic approach to neuropathological disorders and/or as adjunct therapies in psychiatric disorders and support the recent broadening of the definition of psychobiotic. Finally, this study supports F. prausnitzii has significant potential as a psychobiotic.

Optimized tableting for extremely oxygen-sensitive probiotics using direct compression.

Faecalibacterium prausnitzii was previously recognized for its intestinal anti-inflammatory activities and it has been shown less abundant in patients with chronic intestinal diseases. However, the main problems encountered in the use of this interesting anaerobic microorganism are firstly its high sensitivity to the oxygen and secondly, its ability to reach the large intestine alive as targeted site. The aim of this study was to investigate the effect of direct compression on the viability of this probiotic strain after different compression pressure and storage using three different excipients (MCC, HPMC and HPMCP). The effect of compression process on cell viability was studied and a strategy was proposed to improve probiotic viability. Results showed that cell viability decreased almost linearly with compression pressure. MCC and HPMC seemed the most favorable carriers and after storage, each tablet exhibited a survival above108 CFU. Storage stability was obtained with a pressure of 201 MPa after 28 days at 25 °C, in anaerobic condition and with 11% relative humidity. Compression after a pre-consolidated stage improved clearly the survival rate due to lower temperature increase and lower shearing force. Thus, direct compression seems to be suitable in producing probiotics tablets with extremely oxygen-sensitive strains, and could provide sufficient protection during storage to expect therapeutic efficiency.

The gut microbiome is required for full protection against acute arsenic toxicity in mouse models.

Arsenic poisons an estimated 200 million people worldwide through contaminated food and drinking water. Confusingly, the gut microbiome has been suggested to both mitigate and exacerbate arsenic toxicity. Here, we show that the microbiome protects mice from arsenic-induced mortality. Both antibiotic-treated and germ-free mice excrete less arsenic in stool and accumulate more arsenic in organs compared to control mice. Mice lacking the primary arsenic detoxification enzyme (As3mt) are hypersensitive to arsenic after antibiotic treatment or when derived germ-free, compared to wild-type and/or conventional counterparts. Human microbiome (stool) transplants protect germ-free As3mt-KO mice from arsenic-induced mortality, but protection depends on microbiome stability and the presence of specific bacteria, including Faecalibacterium. Our results demonstrate that both a functional As3mt and specific microbiome members are required for protection against acute arsenic toxicity in mouse models. We anticipate that the gut microbiome will become an important explanatory factor of disease (arsenicosis) penetrance in humans, and a novel target for prevention and treatment strategies.

Faecalibacterium prausnitzii treatment improves hepatic health and reduces adipose tissue inflammation in high-fat fed mice.

Faecalibacterium prausnitzii is considered as one of the most important bacterial indicators of a healthy gut. We studied the effects of oral F. prausnitzii treatment on high-fat fed mice. Compared to the high-fat control mice, F. prausnitzii-treated mice had lower hepatic fat content, aspartate aminotransferase and alanine aminotransferase, and increased fatty acid oxidation and adiponectin signaling in liver. Hepatic lipidomic analyses revealed decreases in several species of triacylglycerols, phospholipids and cholesteryl esters. Adiponectin expression was increased in the visceral adipose tissue, and the subcutaneous and visceral adipose tissues were more insulin sensitive and less inflamed in F. prausnitzii-treated mice. Further, F. prausnitzii treatment increased muscle mass that may be linked to enhanced mitochondrial respiration, modified gut microbiota composition and improved intestinal integrity. Our findings show that F. prausnitzii treatment improves hepatic health, and decreases adipose tissue inflammation in mice and warrant the need for further studies to discover its therapeutic potential.

Microbiota dysbiosis in inflammatory bowel diseases: in silico investigation of the oxygen hypothesis.

BACKGROUND: Inflammatory bowel diseases (IBD), which include ulcerative colitis and Crohn's disease, cause chronic inflammation of the digestive tract in approximately 1.6 million Americans. A signature of IBD is dysbiosis of the gut microbiota marked by a significant reduction of obligate anaerobes and a sharp increase in facultative anaerobes. Numerous experimental studies have shown that IBD is strongly correlated with a decrease of Faecalibacterium prausnitzii and an increase of Escherichia coli. One hypothesis is that chronic inflammation induces increased oxygen levels in the gut, which in turn causes an imbalance between obligate and facultative anaerobes. RESULTS: To computationally investigate the oxygen hypothesis, we developed a multispecies biofilm model based on genome-scale metabolic reconstructions of F. prausnitzii, E. coli and the common gut anaerobe Bacteroides thetaiotaomicron. Application of low bulk oxygen concentrations at the biofilm boundary reproduced experimentally observed behavior characterized by a sharp decrease of F. prausnitzii and a large increase of E. coli, demonstrating that dysbiosis consistent with IBD disease progression could be qualitatively predicted solely based on metabolic differences between the species. A diet with balanced carbohydrate and protein content was predicted to represent a metabolic "sweet spot" that increased the oxygen range over which F. prausnitzii could remain competitive and IBD could be sublimated. Host-microbiota feedback incorporated via a simple linear feedback between the average F. prausnitzii concentration and the bulk oxygen concentration did not substantially change the range of oxygen concentrations where dysbiosis was predicted, but the transition from normal species abundances to severe dysbiosis was much more dramatic and occurred over a much longer timescale. Similar predictions were obtained with sustained antibiotic treatment replacing a sustained oxygen perturbation, demonstrating how IBD might progress over several years with few noticeable effects and then suddenly produce severe disease symptoms. CONCLUSIONS: The multispecies biofilm metabolic model predicted that oxygen concentrations of ∼1 micromolar within the gut could cause microbiota dysbiosis consistent with those observed experimentally for inflammatory bowel diseases. Our model predictions could be tested directly through the development of an appropriate in vitro system of the three species community and testing of microbiota-host interactions in gnotobiotic mice.

Anti-nociceptive effect of Faecalibacterium prausnitzii in non-inflammatory IBS-like models.

Visceral pain and intestinal dysbiosis are associated with Irritable Bowel Syndrome (IBS), a common functional gastrointestinal disorder without available efficient therapies. In this study, a decrease of Faecalibacterium prausnitzii presence has been observed in an IBS-like rodent model induced by a neonatal maternal separation (NMS) stress. Moreover, it was investigated whether F. prausnitzii may have an impact on colonic sensitivity. The A2-165 reference strain, but not its supernatant, significantly decreased colonic hypersensitivity induced by either NMS in mice or partial restraint stress in rats. This effect was associated with a reinforcement of intestinal epithelial barrier. Thus, F. prausnitzii exhibits anti-nociceptive properties, indicating its potential to treat abdominal pain in IBS patients.