The influence of gut microbiome-related lipids and glycans upon intestinal colonisation, and the impact of faecal microbiota transplant

Antibiotics are life-saving treatments for bacterial infections, but there may be (collateral damage) with overuse upon the gut microbiome (i.e. the billions of microorganisms within the gut). Specifically, any associated loss of (beneficial) commensal gut bacteria results in loss of their ability to protect against disease-causing (pathogenic) bacteria causing gut infections, e.g.

Clostridioides difficile infection (CDI). Similarly, recurrent antimicrobials (select out) gut bacteria with antimicrobial resistance (AMR), increasing vulnerability to the presence of intestinal multidrug resistant organisms (MDROs). Currently, we have limited therapeutic strategies to minimise this problem; however, one approach to restore the antibiotic-damaged microbiome is faecal microbiota transplant (FMT; stool microbiome transfer from healthy screened donor into a patient).

FMT is an established treatment for CDI, and shows promise in patients colonised with (carriers of) intestinal MDROs.

However, we do not fully understand how antibiotics produce these (side effects), and have limited knowledge about mechanisms of action of FMT, although the more donor microbiome engrafting (taking hold) within the recipient, the more likely success. Better understanding of how antibiotics and FMT impact the gut microbiome to respectively increase vulnerability to/ protect against (antibiotic-associated infections) - including factors influencing FMT's engraftment - could be exploited to develop more effective (microbiome therapeutics).

One mediator of FMT's effectiveness are metabolites (small chemical molecules). My research demonstrates that patients with an antibiotic-damaged gut microbiome have alterations in various lipid (fat-related) gut metabolites related to the microbiome compared to healthy people, and these are restored (to normal) by FMT. This includes a post-FMT reduction in certain lipids containing sulfate groups, including a group called sulfatides.

Further research demonstrates that FMT restores 'beneficial' bacteria possessing (sulfatase) enzymes (which remove the sulfate group from gut lipids, as well as molecules on our own (host cells called glycans); FMT also restores bacterial enzymes that chemically alter glycans. This is interesting, as sulfatides and sulfated glycans - but not desulfated versions - are associated with gut colonisation of disease-associated bacteria or common MDROs (such as C. difficile, E. coli and K. pneumoniae), and binding of their toxins (poisons), enabling them to attack the gut.

I hypothesise that antibiotics causes loss of beneficial gut bacteria (containing sulfatases and glycan-altering enzymes) which protect against gut colonisation with pathogenic bacteria and their toxins; successful FMT reverses this and restores engraftment with these beneficial bacteria instead.