Essay Example on One of the most microbial rich niches is located in the human body








Summary Willem de Vos Summary Introduction One of the most microbial rich niches is located in the human body The Gram negative anaerobe Akkemansia muciniphila which belongs to the Planctomycetes Verrucomicrobia Chlamydiae superphylum is found in the alimentary canal of more than 90 of the evaluated cases A muciniphila is well adapted to the human gut environment and uses 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 the abundance of A muciniphila For example when the density of A muciniphila is low this 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 and decreasing endotoxemia are associated with A muciniphila State of the art There is not much known about the interactions between A muciniphila and the host nor how it handles the different environmental circumstances Previous studies do suggest that there is a positive consequence for the health of the gastrointestinal tract when

A muciniphila is present but further investigation is needed for future application The interaction of the bacteria and its hosts starts with colonizing in which they can adhere by binding to the mucus layer of the intestines epithelium or via the cells underneath the enterocytes It is unclear to which components A muciniphila binds neither has been studies whether it is able survive in an oxygen rich setting This study will answer which mechanisms A muciniphila uses to adhere to the mucus layer or the epithelium cells of the gastrointestinal tract Recent findings Although the human colon mainly consists out of an anaerobic microbe community doesn't mean that all microbes are intolerant to oxygen The results suggest that A muciniphila is able to cope in oxic and anoxic environments As A muciniphila is aerotolerant contrasting incubation conditions were compared in an adhesion experiment The binding efficiency with epithelial cells HT29 and Caco 2 do not differ between aerobic and anaerobic atmosphere Thus A muciniphila does not have to be treated as a true anaerobe but is able to cope with oxygen Also it turned out that the only significant binding of A muciniphila compared to BSA occurred with laminin The binding process of A muciniphila with other extracellular matrix ECM proteins was not significant As the adhesion between A muciniphila and the intestinal mucus is less than 1 it can be stated that there is no adhesion at all Several bacteria are known for binding to the colonic mucus and therefor it was unexpected that 

A muciniphila did not attach to the colonic mucus An explanation for this is that these species do not utilize and degrade the mucus like A muciniphila does Although the adhesion of A muciniphila and L rhamnosus on colonic mucus was not comparable A muciniphila adhered to both enterocytes equally well as L rhamnosus This might indicate that the enterocytes are true binding sites for A muciniphila A muciniphila and B fragilis were both co cultivated for 24 hours and indicated an expansion in transepithelial electrical resistance TER Compared to the Caco 2 cultures without bacteria the TER of Caco 2 cocultures of Escherichia coli declined significantly This shows that at this time point E coli cells increased and that there is no cell interruption for the OD600 values of A muciniphila and B fragilis which indicates a stagnation of growth The positive impact of cell monolayer integrity for the first 24 hours was the most successful 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 cocultures of B fragilis During the 48 hour incubation the cell density of B fragilis and A muciniphila did not diversify neither seems that the bacteria are severly affected Under the same circumstances E coli affected TER development negatively During the second 24 hours the coculture increased suggesting that the transepithelial electrical resistance in E coli cocultures will further decline Earlier studies have associated obesity and diabetes to decreased gut health and inflammation which result in lipopolysaccharide LPS induced endotoxemia 

When LPS is released enterocytes start producing the chemokine interleukin 8 IL 8 which leads to inflammation Needless inflammation can cause disorder in the intestinal epithelium and can disturb the homeostasis of the colonial mucus The production of IL 8 in HT 29 cells was lower in A muciniphila when compared to the IL 8 production of E coli Thus there will be no strong inflammation when A muciniphila is present in the gastrointestinal tract Because in the presence of A muciniphila almost no inflammatory reaction was induced it was checked whether it does or does not produce LPS and whether it is different compared to E coli This study indicates that LPS is produced by A muciniphila but no HT 29 cells were activated to produce interleukin 8 Therefor it is likely that the produced LPS by A muciniphila is different compared to that of E coli Discussion The results show that A muciniphila does not bind to the intestinal mucus but prefers to bind to the epithelial cells Caco 2 and HT 29 and the ECM laminin It remains unknown how this organism is able to live in this continually adjusting habitat and should be further investigated to answer this question A possible justification why A muciniphila is not able to effectively bind to the intestinal mucus is because A muciniphila might release a certain stimulus which attacks the mucus It is likely that different microbes are competing among each other for binding sites as both pathogens and A muciniphila want to bind on damaged parts of the intestines It is therefore likely that A muciniphila is able to strengthen the barrier of the intestinal tract Future research could study the helpful role of A muciniphila in connection with its host in for example obesity and diabetes

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