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]

Faecalibacterium
Scientific classification
Domain:	Bacteria
Phylum:	Bacillota
Class:	Clostridia
Order:	Oscillospirales
Family:	Ruminococcaceae
Genus:	Faecalibacterium Duncan et al., 2002
Species:	F. prausnitzii F. butyricigenerans F. longum
Binomial name
Faecalibacterium prausnitzii Faecalibacterium butyricigenerans (Hauduroy et al., 1937) Duncan et al., 2002 Zou 2021

History

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.

Genetics

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 in laboratory conditions

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.

Clinical relevance

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-inflmmatory 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]} and higher than usual levels have been associated with psoriasis.^[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]

Faecalibacterium prausnitzii and other bacteria

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]

Inflammatory bowel disease

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]

Biomarker relevance

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]

See also

• IMPDH RNA motif, a transcription regulator in Faecalibacterium

References

1. Zou, Yuanqiang; Lin, Xiaoqian; Xue, Wenbin; Tuo, Li; Chen, Ming-Sheng; Chen, Xiao-Hui; Sun, Cheng-hang; Li, Feina; Liu, Shao-wei; Dai, Ying; Kristiansen, Karsten; Xiao, Liang (2021-05-31). "Characterization and description of Faecalibacterium butyricigenerans sp. nov. and F. longum sp. nov., isolated from human faeces". Scientific Reports. 11 (1): 11340. doi:10.1038/s41598-021-90786-3. ISSN 2045-2322. PMC 8166934.
2. Sakamoto, Mitsuo; Sakurai, Naomi; Tanno, Hiroki; Iino, Takao; Ohkuma, Moriya; Endo, Akihito (2022). "Genome-based, phenotypic and chemotaxonomic classification of Faecalibacterium strains: proposal of three novel species Faecalibacterium duncaniae sp. nov., Faecalibacterium hattorii sp. nov. and Faecalibacterium gallinarum sp. nov". International Journal of Systematic and Evolutionary Microbiology. 72 (4): 005379. doi:10.1099/ijsem.0.005379. ISSN 1466-5034.
3. Martín R, Miquel S, Benevides L, Bridonneau C, Robert V, Hudault S, et al. (2017). "Functional Characterization of Novel Faecalibacterium prausnitzii Strains Isolated from Healthy Volunteers: A Step Forward in the Use of F. prausnitzii as a Next-Generation Probiotic". Frontiers in Microbiology. 8: 1226. doi:10.3389/fmicb.2017.01226. PMC 5492426. PMID 28713353.
4. Khan MT, Duncan SH, Stams AJ, van Dijl JM, Flint HJ, Harmsen HJ (August 2012). "The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic-anoxic interphases". The ISME Journal. 6 (8): 1578–1585. doi:10.1038/ismej.2012.5. PMC 3400418. PMID 22357539.
5. Bag S, Ghosh TS, Das B (November 2017). "Complete Genome Sequence of Faecalibacterium prausnitzii Isolated from the Gut of a Healthy Indian Adult". Genome Announcements. 5 (46). doi:10.1128/genomeA.01286-17. PMC 5690339. PMID 29146862.
6. Lopez-Siles M, Duncan SH, Garcia-Gil LJ, Martinez-Medina M (April 2017). "Faecalibacterium prausnitzii: from microbiology to diagnostics and prognostics". The ISME Journal. 11 (4): 841–852. doi:10.1038/ismej.2016.176. PMC 5364359. PMID 28045459.
7. Duncan SH, Hold GL, Harmsen HJ, Stewart CS, Flint HJ (November 2002). "Growth requirements and fermentation products of Fusobacterium prausnitzii, and a proposal to reclassify it as Faecalibacterium prausnitzii gen. nov., comb. nov". International Journal of Systematic and Evolutionary Microbiology. 52 (Pt 6): 2141–2146. doi:10.1099/00207713-52-6-2141. PMID 12508881.
8. Miquel S, Martín R, Rossi O, Bermúdez-Humarán LG, Chatel JM, Sokol H, et al. (June 2013). "Faecalibacterium prausnitzii and human intestinal health". Current Opinion in Microbiology. 16 (3): 255–261. doi:10.1016/j.mib.2013.06.003. PMID 23831042.
9. "Summary of Faecalibacterium prausnitzii, Strain A2-165, version 21.5". BioCyc.
10. Lopez-Siles M, Khan TM, Duncan SH, Harmsen HJ, Garcia-Gil LJ, Flint HJ (January 2012). "Cultured representatives of two major phylogroups of human colonic Faecalibacterium prausnitzii can utilize pectin, uronic acids, and host-derived substrates for growth". Applied and Environmental Microbiology. 78 (2): 420–428. Bibcode:2012ApEnM..78..420L. doi:10.1128/AEM.06858-11. PMC 3255724. PMID 22101049.
11. Quévrain E, Maubert MA, Michon C, Chain F, Marquant R, Tailhades J, et al. (March 2016). "Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease". Gut. 65 (3): 415–425. doi:10.1136/gutjnl-2014-307649. PMC 5136800. PMID 26045134.
12. Wrzosek L, Miquel S, Noordine ML, Bouet S, Joncquel Chevalier-Curt M, Robert V, et al. (May 2013). "Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent". BMC Biology. 11 (1): 61. doi:10.1186/1741-7007-11-61. PMC 3673873. PMID 23692866.
13. He X, Zhao S, Li Y (2021-03-05). "Faecalibacterium prausnitzii: A Next-Generation Probiotic in Gut Disease Improvement". Canadian Journal of Infectious Diseases and Medical Microbiology. 2021: e6666114. doi:10.1155/2021/6666114. ISSN 1712-9532.
14. Inan MS, Rasoulpour RJ, Yin L, Hubbard AK, Rosenberg DW, Giardina C (April 2000). "The luminal short-chain fatty acid butyrate modulates NF-kappaB activity in a human colonic epithelial cell line". Gastroenterology. 118 (4): 724–734. doi:10.1016/s0016-5085(00)70142-9. PMID 10734024.
15. Zhang, Jianbo; Huang, Yu-Ja; Yoon, Jun Young; Kemmitt, John; Wright, Charles; Schneider, Kirsten; Sphabmixay, Pierre; Hernandez-Gordillo, Victor; Holcomb, Steven J.; Bhushan, Brij; Rohatgi, Gar; Benton, Kyle; Carpenter, David; Kester, Jemila C.; Eng, George (January 2021). "Primary Human Colonic Mucosal Barrier Crosstalk with Super Oxygen-Sensitive Faecalibacterium prausnitzii in Continuous Culture". Med. 2 (1): 74–98.e9. doi:10.1016/j.medj.2020.07.001. ISSN 2666-6340. PMC 7839961. PMID 33511375.
16. Miquel S, Leclerc M, Martin R, Chain F, Lenoir M, Raguideau S, et al. (April 2015). Blaser MJ (ed.). "Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii". mBio. 6 (2). doi:10.1128/mBio.00300-15. PMC 4453580. PMID 25900655.
17. Qiu X, Zhang M, Yang X, Hong N, Yu C (December 2013). "Faecalibacterium prausnitzii upregulates regulatory T cells and anti-inflammatory cytokines in treating TNBS-induced colitis". Journal of Crohn's & Colitis. 7 (11): e558–e568. doi:10.1016/j.crohns.2013.04.002. PMID 23643066.
18. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán LG, Gratadoux JJ, et al. (October 2008). "Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients". Proceedings of the National Academy of Sciences of the United States of America. 105 (43): 16731–16736. doi:10.1073/pnas.0804812105. PMC 2575488. PMID 18936492.
19. "Bacterium 'to blame for Crohn's'". BBC News. 2008-10-21. Retrieved 2008-10-21.
20. Newton RJ, McLellan SL, Dila DK, Vineis JH, Morrison HG, Eren AM, Sogin ML (February 2015). "Sewage reflects the microbiomes of human populations". mBio. 6 (2): e02574. doi:10.1128/mBio.02574-14. PMC 4358014. PMID 25714718.
21. Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, et al. (August 2015). "Altered fecal microbiota composition in patients with major depressive disorder". Brain, Behavior, and Immunity. 48: 186–194. doi:10.1016/j.bbi.2015.03.016. PMID 25882912.
22. Codoñer FM, Ramírez-Bosca A, Climent E, Carrión-Gutierrez M, Guerrero M, Pérez-Orquín JM, et al. (February 2018). "Gut microbial composition in patients with psoriasis". Scientific Reports. 8 (1): 3812. Bibcode:2018NatSR...8.3812C. doi:10.1038/s41598-018-22125-y. PMC 5830498. PMID 29491401.
23. Stenman LK, Burcelin R, Lahtinen S (February 2016). "Establishing a causal link between gut microbes, body weight gain and glucose metabolism in humans - towards treatment with probiotics". Beneficial Microbes. 7 (1): 11–22. doi:10.3920/BM2015.0069. PMID 26565087.
24. Rossi O, van Berkel LA, Chain F, Tanweer Khan M, Taverne N, Sokol H, et al. (January 2016). "Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses". Scientific Reports. 6 (1): 18507. Bibcode:2016NatSR...618507R. doi:10.1038/srep18507. PMC 4698756. PMID 26725514.
25. Laval L, Martin R, Natividad JN, Chain F, Miquel S, Desclée de Maredsous C, et al. (2015-01-02). "Lactobacillus rhamnosus CNCM I-3690 and the commensal bacterium Faecalibacterium prausnitzii A2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice". Gut Microbes. 6 (1): 1–9. doi:10.4161/19490976.2014.990784. PMC 4615674. PMID 25517879.
26. Licht TR, Hansen M, Bergström A, Poulsen M, Krath BN, Markowski J, et al. (January 2010). "Effects of apples and specific apple components on the cecal environment of conventional rats: role of apple pectin". BMC Microbiology. 10 (1): 13. doi:10.1186/1471-2180-10-13. PMC 2822772. PMID 20089145.
27. Cheng L, Kiewiet MB, Logtenberg MJ, Groeneveld A, Nauta A, Schols HA, et al. (2020). "Effects of Different Human Milk Oligosaccharides on Growth of Bifidobacteria in Monoculture and Co-culture With Faecalibacterium prausnitzii". Frontiers in Microbiology. 11: 569700. doi:10.3389/fmicb.2020.569700. PMC 7662573. PMID 33193162.
28. Wright EK, Kamm MA, Teo SM, Inouye M, Wagner J, Kirkwood CD (June 2015). "Recent advances in characterizing the gastrointestinal microbiome in Crohn's disease: a systematic review". Inflammatory Bowel Diseases. 21 (6): 1219–1228. doi:10.1097/MIB.0000000000000382. PMC 4450900. PMID 25844959.
29. El Hage R, Hernandez-Sanabria E, Van de Wiele T (2017-09-29). "Emerging Trends in "Smart Probiotics": Functional Consideration for the Development of Novel Health and Industrial Applications". Frontiers in Microbiology. 8: 1889. doi:10.3389/fmicb.2017.01889. PMC 5626839. PMID 29033923.
30. Gerasimidis K, Russell R, Hansen R, Quince C, Loman N, Bertz M, et al. (July 2014). "Role of Faecalibacterium prausnitzii in Crohn's Disease: friend, foe, or does not really matter?". Inflammatory Bowel Diseases. 20 (7): E18–E19. doi:10.1097/MIB.0000000000000079. PMID 24859302.
31. Diederen K, Li JV, Donachie GE, de Meij TG, de Waart DR, Hakvoort TB, et al. (November 2020). "Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn's disease". Scientific Reports. 10 (1): 18879. Bibcode:2020NatSR..1018879D. doi:10.1038/s41598-020-75306-z. PMC 7609694. PMID 33144591.
32. Lopez-Siles M, Martinez-Medina M, Abellà C, Busquets D, Sabat-Mir M, Duncan SH, et al. (November 2015). Elkins CA (ed.). "Mucosa-associated Faecalibacterium prausnitzii phylotype richness is reduced in patients with inflammatory bowel disease". Applied and Environmental Microbiology. 81 (21): 7582–7592. Bibcode:2015ApEnM..81.7582L. doi:10.1128/AEM.02006-15. PMC 4592880. PMID 26296733.
33. Swidsinski A, Loening-Baucke V, Vaneechoutte M, Doerffel Y (February 2008). "Active Crohn's disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora". Inflammatory Bowel Diseases. 14 (2): 147–161. doi:10.1002/ibd.20330. PMID 18050295. S2CID 46449782.