Week 22: Mycobacterium vaccae, Jenifer Wightman, Graham A.W. Rook

Cover Image. Mycobacterium vaccae, from Microbiology in Pictures, n.d.

Waning gibbous moon; 21 days to summer solstice.

This week goes long on history and biology—the latter not my forte. Bear with me as I venture into the science of the small. The surprising story is worth it.

Headnote

They’re in the soil. You may have heard that a single teaspoon of soil contains tens of billions of individual microorganisms—far more than the total population of currently living humans, and perhaps approaching the total number of humans who have ever walked this planet. Indeed, recent research suggests that more than half of all species on Earth dwell primarily beneath our feet, in the microcosmos of infinitesimal life. And common among these tiny dirt dwellers are some very interesting and important “old friends” that we humans should get to know better: bacteria, parasites, and other microbes (viruses, fungi, and protozoa) that offer many known and potential benefits to humans.

In his 1665 book, Micrographia, English scientist Robert Hooke produced a striking illustration of the fruiting structures of “blue mould” (something in the genus Mucor), thereby offering humans our first glimpse of the microscopic realm. When the eccentric Dutch experimentalist Antonie van Leeuwenhoek first observed bacteria in 1676, he referred to the amusing little things he observed squirming in water as “animalcules.” Scientific wonder at these tiny forms grew into public fear roughly two centuries later, when the germ theory of disease gradually replaced belief in miasmas, and biologists realized that bacteria were responsible for horrifying diseases such as tuberculosis and leprosy.

By the beginning of the twenty-first century, though, things have come full circle. We now know that bacteria and other microorganisms, even viruses and parasites, operate as an “invisible organ,” hidden body, or “second human genome” within us, playing many crucial roles: digesting complex carbohydrates, producing essential vitamins, educating our immune systems, and shielding the body from harmful pathogens. We are, in fact, holobionts. Microbes also play crucial roles outside of our bodies, in agriculture and food preparation, industry and biotechnology—microscopic cyanobacteria, after all, generated the planet’s breathable atmosphere. How did we get here?

In 1971, immunologists noticed that people living near Lake Kyoga in central Uganda responded better to the vaccine for leprosy than people in other regions of the world. They connected this vaccine response to a strain of Mycobacteria vaccae (from vacca, Latin for “cow,” from which, via cowpox, we also get the word vaccine).* This bacteria was so abundant in the local environment that it lent a bright orange-yellow tint to the mud surrounding the lake. Thus began a radical revision of modern germ theory. The existence of good germs means that sterility is not synonymous with health; and while hygiene is still crucial, so is biodiversity—not just out in nature, but around us and inside us.

When later researchers tested Mycobacteria vaccae as an immunotherapy for lung cancer patients, they were surprised to find that, although treatment did not extend the patients lives, it significantly improved their mental health. Why this unexpected side effect? Follow-up studies identified the specific mechanism, revealing that exposure to the bacteria stimulated serotonin production and helped regulate stress responses in mice. The notion of a “dirt antidepressant” made headlines, further research confirmed the near-immediate benefits of direct contact with plants and soil, and wellness entrepreneurs rushed to commoditize yet another miracle-promising supplement. Pardon me if I go do some weeding in my garden instead.

Mycobacterium vaccae is a nonpathogenic bacteria commonly found in soil around the world. It is a saprophyte, or saprotroph, meaning that it feeds off of decaying matter, secreting enzymes to break down dead organic matter or waste and absorbing whatever nutrients emerge. This bacteria has extensive immunoregulatory and anti-inflammatory properties that are being explored; and, through microbial prospecting, a strain of it can even be used to find oil. The Mycobacteriumgenus includes several infamous disease-causing species, including those responsible for tuberculosis and leprosy. But other mycobacteria are being studied for potential medical and health applications, ranging from treatment of cancers (Mycobacterium obuense) and allergy-induced asthma (Mycobacterium phlei) to remediation of polluted soils (Mycobacterium chitae). After a week of perusing the bacterial universe, I feel that I’ve only scratched the surface.

Fig. 2. Jenifer Wightman, Winogradsky Rothko (2004). Six weeks after installation. Photo: Johnna MacArthur (September 11, 2004).

Readings

1. Bacteria are the original synthesizers. Although bacteria are simple single cell organisms, they are a biological force adapting to and accessing minute resources in severe climates such as the Arctic or the deep sea. This adaptability has made bacteria the most genetically diverse and abundant (in mass and number) organisms. In their chemical and physical resource cultivation, they impact both their micro and macro ecosystems. On the macro scale, for example, bacteria generated oxygen stores that contributed to the creation of the ozone layer. The ozone layer was critical in reducing harmful effects of sunlight on evolving DNA. Bacteria also created greenhouse gases to warm the earth so that the climate was ripe for evolution of higher organisms. Even now, bacteria are profound players in the contemporary terrestrial economy.

   Bacteria thrive if conditions are favorable; they mutate, migrate, die, or lie

   senescent if conditions are not favorable. They consume, reproduce, deplete their resources, and release waste products. As bacteria express themselves (i.e. live), they alter their habitat. They synthesize new environments or landscapes, thereby producing new ecological niches for other organisms. As such, they offer a field for mapping the rhythms and patterns constitutive of life.

Jenifer Wightman, “Winogradsky Rothko: Bacterial Ecosystem as Pastoral Landscape.” Journal of Visual Culture 7.3 (December 2008: 309-334), p. 312.

2. Which organisms from the natural environment are important in addition to those from animals? Although there is no direct evidence linking soil consumption to health benefits, it is evident that soil is a significant source of microbial exposure in natural settings. Soil microorganisms become airborne in dust during dry conditions, but also when raindrops impact the soil, because tiny explosions of soil organisms occur, releasing them into the air. Additionally, soil organisms settle on food, particularly in farmers' markets where washing and packaging are minimal. Moreover geophagy (consumption of soil) is an evolved behaviour. It is probable that all vertebrates, especially in early life, engage in it, and the green iguana is a well-studied example of this. Many primate species, including gorillas, orangutans, and chimpanzees have been observed eating soil. Geophagy is a common practice in many cultures, and is frequently observed during pregnancy, not only in underdeveloped rural societies but also in Western cultures where it is often considered a pathological manifestation of pica. Many of the Treg-inducing and immunoregulation-enhancing strains of bacteria are found in soil.

Graham A.W. “The Old Friends Hypothesis: Evolution, Immunoregulation and Essential Microbial Inputs.” Frontiers of Allergy 4 (September 12, 2023), p. 8.

3. Context Inflammation is increasingly recognized as contributing to the pathogenesis of major depressive disorder (MDD), even in individuals who are otherwise medically healthy. Most studies in search of sources for this increased inflammation have focused on factors such as psychosocial stress and obesity that are known to activate inflammatory processes and increase the risk for depression. However, MDD may be so prevalent in the modern world not just because proinflammatory factors are widespread, but also because we have lost contact with previously available sources of anti-inflammatory, immunoregulatory signaling.
   
   Objective To examine evidence that disruptions in coevolved relationships with a variety of tolerogenic microorganisms that were previously ubiquitous in soil, food, and the gut, but that are largely missing from industrialized societies, may contribute to increasing rates of MDD in the modern world.
   
   […]
   
   Conclusion Measured exposure to the old friends or their antigens may offer promise for the prevention and treatment of MDD in modern industrialized societies.

Charles L. Raison, Christopher A. Lowry, and Graham A.W. Rook. "Inflammation, Sanitation, and Consternation: Loss of Contact With Coevolved, Tolerogenic Microorganisms and the Pathophysiology and Treatment of Major Depression." Archives of General Psychiatry67.12 (December 2010): 1211–1224.

Supplementum

• “Getting Dirty May Lift Your Mood,” University of Bristol (April 2, 2007)."

• Lisa Marshall, “Stalking the Dirt Vaccine.” Colorado Arts and Sciences Magazine (The University of Colorado Boulder: September 28, 2018).

• Chris Lowry, “The Old Friends Hypothesis & the M. Vaccae Story.” The Microbiome Summit (2019).

• “Soil Quotes,” U.S. Department of Agriculture, Natural Resources Conservation Service (n.d.).

• Antoni Van Leeuwenhoek, “Observations, communicated to the publisher by Mr. Antony van Leewenhoeck, in a dutch letter of the 9th Octob. 1676. here English'd: concerning little animals by him observed in rain-well-sea- and snow water; as also in water wherein pepper had lain infused.” Philosophical Transactions R. Society 12.133 (March 25, 1677): 821–831.

Fig. 3. “Scanning electron microscopy analysis of colony variants of M. vaccae. (A) smooth; (B) rough,” from Elisabeth Rodriguez-Guell, et al.(2006).

* In 2018, the Lake Kyoga strain was reclassified as a distinct species, Mycobacterium kyogaense. This sort of thing seems to happen a lot with bacteria.