Faecalibacterium

Faecalibacterium is a genus of bacteria. The genus contains several species including Faecalibacterium prausnitzii, Faecalibacterium butyricigenerans, Faecalibacterium longum,^[1] Faecalibacterium duncaniae, Faecalibacterium hattorii, and Faecalibacterium gallinarum.^[2] Its first known species, Faecalibacterium prausnitzii (renamed as Faecalibacterium duncaniae) is gram-positive,^[3] mesophilic, rod-shaped,^[3] and anaerobic,^[4] and is one of the most abundant and important commensal bacteria of the human gut microbiota. It is non-spore forming and non-motile.^[5] These bacteria produce butyrate and other short-chain fatty acids through the fermentation of dietary fiber. The production of butyrate makes them an important member of the gut microbiota, fighting against inflammation.^[6]

Formerly considered to be a member of Fusobacterium, the bacterium is named in honor of German bacteriologist Otto Prausnitz. In 2002, it was proposed to be reclassified as its own genus, Faecalibacterium, containing the species Faecalibacterium prausnitzii, as phylogenetic analysis from isolates showed it to be only distantly related to Fusobacterium, and a closer member of Clostridium cluster IV.^[7] The bacterium is a gram-negative bacteria, as first classified to the Fusobacterium, however it stains as a gram-positive bacteria.^[8] This can be alluded to the fact that it lacks lipopolysaccharides on its outer membrane, so it stains more closely to gram-positive bacteria, than to gram-negative.

Faecalibacterium prausnitzii has a genome 2,868,932 bp long and has a GC-content of 56.9%. The bacterium has been found to have 2,707 coding sequences, including 77 RNAs encoding genes.^[5] 128 metabolic pathways have been reconstructed, as well as 27 protein complexes and 64 tRNAs.^[9] Phylogenetically, the strains of F. prausnitzii compose phylogroups I and II. Most of the new isolates of this species isolated by Muhammad Tanweer Khan belong to phylogroup II.^[10] A protein produced by this bacterium has been linked to anti-inflammatory effects.^[11]

Faecalibacterium prausnitzii is strictry anaerobic, making it a very difficult bacteria to culture in laboratory conditions. However, there are certain conditions and media, which make it possible to culture even outside of the intestine. The rich medium YCFA is very suitable for the growth of this bacteria in anaerobic conditions.^[12] Another media suitable for the growth of F. prausnitzii is YBHI.^[12] Any liquid media or agar plates should be pretreated beforehand for 24 hours in an anaerobic chamber, to ensure they are completely anaerobic.

In healthy adults, Faecalibacterium prausnitzii represent approximately 5% of the total fecal microbiota but this can increase to around 15% in some individuals, making it one of the most common gut bacteria.^[8] It has anti-inflammatory properties and may improve the imbalance in intestinal bacteria that leads to dysbiosis.^[8] It is one of the main producers of butyrate in the intestine. Since butyrate inhibits the production of NF-kB and IFN-y, both involved in the pro-inflammatory response, Faecalibacterium prausnitzii acts as an anti-inflammatory gut bacterium.^[13][14][15] By blocking the NF-kB pathway, F. prausnitzii indirectly inhibts the production of the pro-inflammatory IL-8, secreted by the intestinal epithelial cells.^[16] Other research has shown that there is a correlation between high populations of Faecalibacterium prausnitzii, low IL-12 abundance, and higher IL-10 production.^[17][18] The upregulated IL-10 inhibts the secretion of IFN-y, TNF-alpha, IL-6, and IL-12, which are all pro-inflammatory cytokines.^[18] Apart from butyrate, F. prausnitzii produce formate and D-lactate as byproducts of fermentation of glucose and acetate.^[13][7] Lower than usual levels of F. prausnitzii in the intestines have been associated with Crohn's disease, obesity, asthma and major depressive disorder.^{[18][19][20][21]} Higher than usual levels of the F06 clade of F. prausnitzii have been associated with atopic dermatitis.^[22] Faecalibacterium prausnitzii can improve gut barrier function.^[23] Supernatant of F. prausnitzii has been shown to improve the gut barrier by affecting the permeability of epithelial cells.^[24] Another way that F. prausnitzii improves the gut barrier is by improving the permiability and the expression of tightly bound proteins - e-cadherin and occludin. Both of them increase the tight junctions between cells, strengthen the gut barrier and alleviate inflammation.^[25][13]

Studies show that F. prausnitzii interacts with other bacteria, which affects its butyrate production, and survival. When F. prausnitzii is cultured with Bacteroides thetaiotaomicron, it produces more butyric acid than standing alone,^[26][12] F. prausnitzii also benefits from growing with certain other bacteria. For example, in order to survive in the gut environment, it requires certain bacteria to be preexisting. B. thetaiotaomicron and Escherichia coli are needed to create a suitable environment for F. prausnitzii by reducing the redox potential and alter the composition of the nutrients.^[27][12]

In Crohn's disease, as of 2015 most studies (with one exception) found reduced levels of F. prausnitzii;^[28] this has been found in both fecal and mucosal samples.^[29] The lower abundance of these bacteria is not only associated to the chance of developing IBD, but also to the chance of relapsing after a successful therapy. People with lower abundance are six times more likely to relapse in the future.^[18] However, it is a fastidious organism sensitive to oxygen and difficult to deliver to the intestine.^[29]

Exclusive enteral nutrition, which is known to induce remission in Crohn's, has been found to reduce F. prausnitzii in responders.^[30] This could be due to the lack of specific nutrients, that the bacteria need to survive.^[31]

F. prausnitzii can also serve as a biomarker discriminating between different intestinal inflammatory conditions. It is a good biomarker to differentiate between Crohn's disease and colorectal cancer.^[32] An even better biomarker is F. prausnitzii in comparison to E. coli as a complementary indicator (F-E index). This index serves really well in differentiating between colorectal cancer and ulcerative colitis.^[32]

Combining both the host serological data plus microbiological indicators could serve as good biomarker, since it has been reported that Crohn's disease and ulcerative colitis can be differentiated based on monitoring of F. prausnitzii in conjunction with leukocyte count.^[33]

• IMPDH RNA motif, a transcription regulator in Faecalibacterium