The Little Things That Mean a Lot

Researchers reveal how trillions of microscopic companions shape our health and connect us to the world.

The Little Things That Mean a Lot
(Flickr/Donny Bliss,NIH)

A recurring theme of "Naturally Riverside" is the interconnectedness of humans to the natural world. But poinsettias, coyotes, peregrine falcons, donkeys and acorn woodpeckers all seem to be a bit arm's length. Are there creatures with which we are even more intimate? What if we could go no further than our own bodies to find a veritable zoo of organisms?

Welcome to the human microbiome! Everyone carries about 2,000 species of microbes, and every individual has a unique combination of such microorganisms. On our skin and hair, throughout our alimentary system, in our lungs, coursing through our circulatory systems and adjacent to every orifice are an array of bacteria, viruses, archaeans, fungi and other single-celled organisms.

When we think of a community, it can be a specific population in a specific location, such as the community of Riversiders. For biologists, the word has a somewhat different meaning: all of the organisms or a set of specific organisms associated with a location or environment. For example, the insect community of Sycamore Canyon Park would include all of the insects in that location, or the aquatic community of the Santa Ana River would be all of the organisms that live in the water of the river. The human microbiome is this sort of biological community.

The human microbiome of the gut has attracted the most scientific attention. This community essentially extends from your mouth down your esophagus to your stomach and intestines and out the end. Weighing about a pound, this assembly of creatures consists of between 1,000 to almost 2,000 species in an adult. Genomic analysis can determine how many species are present, but if a species hasn't been identified and described then it remains as a "known unknown." About half of the microbe species in a given gut are undescribed.

There are a LOT of microbial individuals crowded into the gut. In a single gram of human feces, there are between 10 billion and 100 billion bacterial cells alone. How many cells are there altogether in a human microbiome compared to the human body? A decent conservative estimate is one-to-one. That is, for every cell that belongs to you, there is a corresponding microbial cell that you are carrying.

Each human has a unique gut microbiome fingerprint; even identical twins do not have identical microbial communities. Nonetheless, there is a sort of structure in terms of similarity. Members of the same household share about 10% of their microbiome. Add a dog to the family, and the similarity rises to 15%. At gross geographic sampling, gut microbiomes are very different indeed when sampled over different continents, especially when diets are different.

I interviewed two University of California at Riverside-based microbiome scientists to help me wrap my head around this intimate, if invisible, world that we carry with us: Professor Quinn McFrederick, director of the Microbiome Initiative at UCR associated with the Department of Entomology, and Assistant Professor Jason Rothman, associated with the Department of Microbiology and Plant Pathology. Both emphasized that diet is more important than geography in determining the makeup of an individual's gut microbiome.

The fact is that at least part of the human gut microbiome interacts positively with the human that carries it. Certainly, some members of the microbiome may be pathogenic, but we generally have good ways of flushing out – so to speak – such nasty microbes. But others may have healthful effects. Professor McFrederick provided the following example: if identical twin mice are raised so that one becomes obese and the other becomes lean, they have vastly different microbiomes. By feeding the lean mouse the microbiome from the obese mouse, the slim mouse begins to put on weight. When the obese mouse is fed the microbiome from the lean mouse, it begins to lose weight.

And some microbes that have healthy effects in the gut might cause havoc elsewhere. For example, the famous and ubiquitous gut bacteria, E. coli, aids digestion. But if it ends up in the urinary tract, the same species can cause an infection.

I purposefully modify my gut microbiome. Being lactose intolerant, I lack the enzyme to digest milk sugar, that is, lactose. If I leave it to my general gut biome, the lactose I consume in dairy products will ferment into noxious products that result in farts, burps, pain and other intestinal distress. But I dose myself daily with a few billion lactobacillus bacteria who can happily digest lactose. No pain, no discomfort from cheese, ice cream, hot dogs, pancakes or other dairy-based foods. Although my case is specific, dosing with "good" microbes is referred to as taking "probiotics." Probiotics are present in a variety of fermented foods that have living cultures; examples include yogurt, kefir, sauerkraut, kombucha and kimchi. Recently, "prebiotic" products have joined probiotics for enhancing your gut microbiomes. Prebiotics are foods that contain complex compounds that probiotic organisms crave but are indigestible without microorganismal assistance.

A so-called healthy gut microbiome is associated with superior digestion, improved defenses against pathogens, vitamin production and other healthful effects. The recognition that there are substantial neural connections between the brain and the gut has called into question whether a healthy microbiome is good for the nervous system. Studies that have removed a healthy microbiome from lab animals have shown an increase in neurological disorders.

In general, it isn't necessary to seek out probiotics and prebiotics to develop and maintain a healthy gut microbiome. Professor Rothman advocates "eating food." Professor McFrederick expands on that to explain that eating whole foods (fresh fruits and veggies, whole grain products, nuts, etc.) and avoiding highly processed foods tends to directly introduce beneficial gut microbes as well as the prebiotic compounds that nourish them.

The key to appreciating the human microbiome is understanding how variable it is. We already know that it varies within an individual over time, between twins and between households. How much does it vary within human communities? Professor Rothman takes regular samples from the Riverside Regional Water Quality Control Plant adjacent to where Van Buren crosses the Santa Ana River. The water is a composite sample of Riverside's wastewater, and therefore, a sample of the 330,000 human microbiomes of the city.

Rather than doing a gross analysis of the water, Rothman concentrates on his specialty, RNA viruses. He was one of the first to demonstrate that the COVID RNA virus makes its way into municipal wastewater; also, he was among the first to measure the relative frequency of different COVID variants in municipal wastewater. Other RNA viruses include the influenza virus. Interestingly, the prominent RNA viruses in Riverside effluent are from plants, notably one type that is a disease agent of tomato. Rothman speculates that we eat plenty of plant viruses from foods that do not require a beautiful exterior (think tomato paste or pasta sauce), and these zoom through our guts.

"At some point, I'm going to sample the grocery shelves and test canned food for plant viruses," he says. "Again, variation is important. Not only between samples, but within samples. On a good day, we can identify about 50% of the viruses present."

Clearly, we are just beginning to learn about our microbiomes – gut, skin and others. With so many species that are unknown, we can only guess what other functions of the microbiome are good for us. But one thing is for sure: for a community of organisms most intimate with our bodies, our interconnectedness with the global microbiome is obvious. We are continuously recruiting new microbes to our bodies and redistributing them back into the environment. The microbiome is yet another way that nature connects us with each other and with the greater living world – naturally, Riverside!


This article benefited from the contributions of Professor Mike Allen, Professor Quinn McFrederick and Professor Jason Rothman.

Glossary

Archaeans: Primitive single-celled organisms that are distinct from and evolved earlier than bacteria.

Microbes: Organisms that cannot be seen without the aid of a microscope.

Microorganisms: Also known as microbes.

Selected References

Martin C.R. et al. 2018. The gut-brain-microbiome axis. Cellular and Molecular Gastroenterology and Hepatology.6:133-148.

Turnbough, P.J. et al. 2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature444:1027-1031.

Walker, A.W. and L. Hoyles. 2023. Human microbiome myths and misconceptions. Nature Microbiology 8: 1392-1396.

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