Summary the human body. The Gram-negative anaerobe Akkemansia

Summary – Willem de VosSummary by Bram Spierings |950620790080 Introduction One of the mostmicrobial rich niches is located in the human body. The Gram-negative anaerobe Akkemansia muciniphila, which belongs tothe Planctomycetes-Verrucomicrobia-Chlamydiae superphylum, is found in the alimentarycanal of more than 90% of the evaluated cases. A. muciniphila is well adapted to the human gut environment anduses glycosolated proteins of the epithelial mucus layer as its C and N source.A study which is conducted earlier suggests that the health of the gastrointestinal tract is correlated with theabundance of A.

muciniphila. For example, whenthe density of A. muciniphila is lowthis is associated to diabetes type 1, Crohn’s disease (CD) and in Ulcerative colitis(UC). Furthermore, the recovery of the mucus layer in the human colon anddecreasing endotoxemia are accociated withA. muciniphila.

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  State of the art There is not muchknown about the interactions between A.muciniphila and the host, nor how it handles the different environmentalcircumstances. Previous studies do suggest that there is a positive consequencefor the health of the gastrointestinaltract when A. muciniphila is present, butfurther investigation is needed for future application. The interaction of thebacteria and its hosts starts with colonizing in whichthey can adhere by binding to the mucus layer of the intestines epithelium or viathe cells underneath, the enterocytes. It is unclear to which components A. muciniphila binds neither has been studies whether it isable survive in an oxygen rich setting.

This study will answer which mechanisms A. muciniphila uses toadhere to the mucus layer or the epithelium cells of the gastrointestinaltract. Recent findings Although the humancolon mainly consists out of an anaerobic microbe community, doesn’t mean thatall microbes are intolerent to oxygen. The results suggest that A. muciniphila is able to cope in oxicand anoxic environments. As A.

muciniphila is aerotolerant, contrasting incubation conditions were compared in an adhesionexperiment. The binding efficiency with epithelial cells  HT29 and Caco-2 do not differ between aerobicand anaerobic atmosphere. Thus, A.muciniphila does not have to be treated as a true anaerobe, but is able tocope with oxygen. Also, it turnedout that the only significant binding of A.muciniphila, compared to BSA, occurred with laminin. The bindingprocess of A. muciniphila with other extracellular matrix (ECM) proteins, was not significant.

Asthe adhesion between A. muciniphila andthe intestinal mucus is less than 1%, it can be stated that there is noadhesion at all. Several bacteria are known for binding to the colonic mucusand therefor it was unexpected that A.muciniphila did not attach to the colonic mucus.

An explanation for this isthat these species do not utilize and degrade the mucus, like A. muciniphila does. Although theadhesion of A. muciniphila and L. rhamnosus on colonic mucus was notcompareble, A.

muciniphila adhered toboth enterocrytes equally well as L.rhamnosus. This might indicate that the enterocytes are true binding sitesfor A. muciniphila. A.

muciniphila and B. fragilis were both cocultivated for 24 hours and indicated an expansionin transepithelial electricalresistance (TER). Compared to the Caco-2 cultures, without bacteria the TER ofCaco-2 cocultures of Escherichia coli declinedsignificantly. This shows that at this timepoint E. coli cells increased and that there is no cell interruption forthe OD600 values of A. muciniphilaand B. fragilis, which indicatesa stagnation of growth.

The positive impact of cell monolayer integrity for thefirst 24 hours was the most succesfull with B.fragilis, followed by A. muciniphila.

After 48 hours the transepithelial electrical resistance of Caco-2 cocultures of A. muciniphila became equal to the coculturesof B. fragilis. During the 48 hour incubation the cell density of B.fragilis and A.

muciniphila did not diversify, neither seems thatthe bacteria are severly affected. Under the same circumstances, E. coliaffected TER development negatively.  Duringthe second 24 hours the coculture increased, suggesting that the transepithelial electrical resistance in E. coli cocultures will furtherdecline.

 Earlier studieshave associated obesity and diabetes to decreased gut health and inflammation,which result in lipopolysaccharide (LPS) induced endotoxemia. When LPS isreleased, enterocytes start producing the chemokine interleukin-8 (IL-8) whichleads to inflammation. Needless inflammation can cause disorder in theintestinal epithelium and can disturb the homeastasis of the colonal mucus. Theproduction of IL-8 in HT-29 cells was lower in A.muciniphila when compared tothe IL-8 production of E.

coli. Thus, there will be no strong inflammationwhen A. muciniphila is present in the gastrointestinal tract. Because in the presence of A.

muciniphilaalsmost no inflammatory reaction was induced, it was checked wether it does ordoes not produce LPS and whether it is different compared to E. coli. Thisstudy indicates that LPS is produced by A. muciniphila but no HT-29cells were activated to produce interleukin-8. Therefor it is likely thatthe produced LPS by A.

muciniphila is different compared to that of E. coli. Discussion The results showthat A. muciniphila does not bind to the intestinal mucus but prefersto bind to the epithelial cells Caco-2 and HT-29 and the ECM laminin. It remains unknown how thisorganism is able to live in this continually adjusting habitat and should befurther investigated to answere this question. A possible justification why A.

muciniphila is not able to effectivelybind to the intestinal mucus is because A.muciniphila might release a certain stimulus which attacks the mucus. It is likely thatdifferent microbes are competing among eachother for bindingsites as bothpathogens and A. muciniphila want tobind on damaged parts of the intestines.

It is therefor likely that A. muciniphila is able to strengthen thebarrier of the intestinal track. Future research could study the helpful roleof A. muciniphila in connection withits host in for example obesity and diabetes.