Microbiome
Microbiota have long been
known to be an unseen, ubiquitous majority teeming on every imaginable surface
upon and within the human body. These surfaces include the (1) conjunctiva, (2)
skin, (3) respiratory tract, (4) gastrointestinal tract, and (5) genitourethral
passages. The approximately 100 trillion bacteria in the human body form 2% to
3% of the average body mass and 55% of the dry feces mass, far outnumbering the 10 trillion human cells. Their aggregate
metabolic activity has earned them the collective name of the “forgotten
organ.”
Contrary to popular belief, many bacteria can be cultured, but the cumbersome
techniques and long incubation periods needed for culture have previously prohibited
the easy identification of bacteria and, in turn, prevented scientific
researchers from grasping their clinical significance. The advent of deep 16S
RNA sequencing has dramatically enhanced our ability to simultaneously and
accurately identify the presence of individual species. Complementing this
technology are the budding sciences of metabolomics and proteomics, which aim
to interpret the clinical impact of the metabolites and proteins generated by
living organisms and tissues. These technologies will reshape our understanding
of how microbiota affect human health and disease. Importantly, this commensal
community does not consist of bacteria alone but also contains countless fungal
and viral agents that cohabitate within an intricate mucosal mosaic.
Maintenance of this complex interplay is thought to be critical to maintaining
mucosal integrity and overall health. On the one hand, innate immunologic and
physiologic mechanisms maintain a healthy community that prevents pathogenic
organisms from flourishing. On the other hand, multiple microbiota mechanisms
promote mucosal integrity and host health. Mucosal surfaces throughout the body
demonstrate convoys of leukocytes regularly deployed for surveil- lance and
phagocytosis of microbial offenders. Salivary enzymes contain lysozymes, IgA,
and peroxidase, which begin the antimicrobial breakdown. The harsh acidity of
gastric secretions is bactericidal. Bile salts serve as detergents and, via
micellar formation, envelop organ- isms, inhibiting their direct mucosal
binding. Pancreatic enzymes break down elements of bacterial cell walls. And,
of course, the migrating motor complex regularly flushes out intestinal
segments, preventing stagnancy and
bacterial overgrowth.
Indeed, a constant drama of urban microwarfare is unfolding, in which
healthy and pathogenic organisms compete for domination and nutritional resources.
For instance, some species will compete for mucosal binding sites to prevent
more invasive pathogenic bacteria from invading and causing illness. In fact,
bacteria are known to secrete lactate, peroxide, and even their own antimicrobial
peptides known as bacteriocins, which serve to keep adjacent competitors at
bay.
Numerous clinical correlates exist to impress upon medical science how
critical these microorganisms are to good health. Initially, a newborn
possesses a sterile gut. It is theorized that early luminal exposures between
the patient’s innate lymphoid system and consumed nutritional elements,
including ingested and inhaled microbiota, will go on to shape the future
development of health and/or disease. For instance, newborns born via cesarean
section rather than natural vaginal delivery are at increased risk for atopic
illnesses such as asthma. Infants who are formula fed rather than breast fed
are at increased risk for allergic disorders. Gut bacteria play an important
role in vitamin K and biotin synthesis.
They also extract short-chain fatty acids from dietary fiber,
specifically butyrate, which promotes colonocyte health. The nonspecific action
of antibiotics disturbs the healthy balance of microbes in the colon; this has
given rise to epidemics of severe Clostridium difficile infection.
Reintroducing healthy donor stool suspensions into an actively infected C.
difficile patient reverses this dysbiosis to a healthy balance with a high
rate of clinical cure. Also, periodontal science has demonstrated that
individuals with tooth and gingival disease are at double the risk for having
coronary artery disease versus their counterparts with a healthy mouth. There is also a suggestion that intestinal
microbiota may influence psychiatric disease; this has given rise to the development
of potential psychobiotics.
Countless studies have provided evidence that the microbiota influence
the immune system via direct and indirect mechanisms. Other disease states
implicated include rheumatologic disease, metabolic syndromes, obesity, and
irritable bowel syndrome. The microbiota represent a new frontier for
therapeutic exploration that may allow us to moderate chronic illness via traditional
medication a d therapeutic multistrain collections of microbiota.
