Image courtesy Elmassry 2020

Advanced methods applied to catalogue the microbial composition of various organs is revealing the astounding fact that no part of the human body is not colonized (or infected) by microbes. Organs previously thought to normally be sterile, such as the uterus, prostate, breasts, urinary bladder, kidneys, eyes, even brain, are proving to be rich with microbes of a variety of sorts: bacterial, Archaeal, viral, fungal. Who would have thought, for instance, that amniotic fluid bathing a developing fetus has its own unique microbiome?

We are walking, talking collections of microbes that some call the “holobiont,” i.e., an aggregate of trillions of living organisms that cohabitate with you as a human being host. It required DNA analysis, rather than crude culture methods, to reveal just how rich, for instance, the normal non-infected urinary bladder is with microbes, or the mouth, teeming with microbes with a density second only to the colon. (Puts a whole new spin on this practice called “kissing,” doesn’t it?)

It means that virtually everything we do—eat, shake hands, swim in a lake, engage in sex, travel to a new environment, lick an ice cream cone, etc.—has some microbial consequence. We cannot therefore separate human from microbial life because they are so intimately intertwined. It means that all human disease, healthcare practices, diet, etc., all need to be reconsidered in light of this universe of life that we previously largely ignored. Many new lessons originate with observations made in so-called “gnotobiotic” animals, i.e., animals raised in completely sterile conditions and thereby lacking a microbiota in all organs, gastrointestinal and otherwise. (Remarkably, the notion of gnotobiosis got its start during the 19th century, advanced during the 1930s, then with more systematic and advanced methods beginning in the 1950s.) While gnotobiotic animals are protected from becoming obese even when fed an unhealthy diet, they also experience unhealthy effects such as an impaired and “immature” immune system, impaired brain maturation and behavior. Such germ-free animals also provide opportunities to observe the effects of re-introducing one or more microbes on the animal’s health and functioning.

Of course, no one has ever created a gnotobiotic human. (Wouldn’t that be interesting? Animals cannot, of course, express feelings or thoughts such as love, hate, anxiety, empathy, generosity, etc.. Only crude indirect observations that hint at such phenomena can be used to infer such internal workings. Imagine what we could learn from a gnotobiotic human about human behavior—creepy but fascinating to consider.) But modern life has conspired to create many dysbiotic humans. Exposure to antibiotics, food additives, herbicides, chlorinated drinking water, synthetic sweeteners, pharmaceuticals, and many other factors has caused fundamental shifts in microbiome composition of virtually all organs, from bladder to brain. We need only compare the microbiomes of indigenous populations unexposed to modern influences, e.g., Yanomami, jungle-dwelling New Guineans, Matses, Masaii, etc. to gain a sense of what adaptation and maladaptation have done to microbial composition in modern humans. They have numerous species we don’t have, we have numerous species they don’t have, with marked differences in relative numbers that both populations share.

As we gain insight into specific disruptions in modern microbiomes, such as the loss of L. reuteri responsible for human behaviors such as love, empathy, generosity, etc., or the loss L gasseri responsible for maintaining “law and order” in the small intestine, or the lack of Leuconostoc mesenteroides and Pediococcus pentosaceus that maintain an intestinal environment conducive to beneficial species, it is becoming clear that, without considering the impact of the microbiome, we are in the dark. Prescribing an antidepressant selective serotonin-reuptake inhibitor, SSRI, for depression, for instance, is a practice that is completely ignorant of the contribution of the microbiome to human mood and behavior. It ignores the fact that Turicibacter sanguinis in the GI tract is responsible for 50% of the entire body’s serotonin production. Social and pharmacologic efforts to stem the tide of suicide (over 35% increase over the last decade) ignore the fact that endogenous oxytocin production, as measured in blood, saliva, and cerebrospinal fluid, is 50% less in people attempting suicide compared to non-suicidal people, a phenomenon that results from dysbiotic loss of L. reuteri.

Do you sense the magnitude of change that we are about to witness? I often compare the emerging insights of microbiome technology with having a Commodore 64 computer in 1982 loaded with Pong. Many people in 1982 thought computers were just a curiosity, a toy for amusement, failing to anticipate computerized, digitized, world-changing technologies such as GPS navigation, cellular communication, self-driving cars and planes, and numerous other innovations that were to follow. I predict that human health and healthcare will become unrecognizably changed in coming decades viewed through 2022 eyes. Stay tuned as we work to decipher and understand these emerging insights.