Science

1.2 Journey to the Center of Ourselves (2)

In the late 1600’s, Antony Leuwenhoek[1]  became the first person to journey into our inner microbial landscape (and write about it). Without access to a fistulated human[2], Leuwenhoek had to limit his exploration to the accessible headwaters of our internal river: the mouth. He obsessively took scrapings of people’s teeth, paying top dollar for scrapings from people with particularly foul breath. Leuwenhoek was rightly convinced that the human organism was more than what he could see. Though his descriptions of the teeming “animalcules” he sent to the Royal Society for publication were (in as an example of peer-review gone wrong) dismissed as the ravings of a man who drank too much, Leuwenhoek’s research contributed to the study of microbes in our human ecosystem.

If the mouth is the headwaters of the GI tract, then the oropharyngeal (throat) cavity is a meeting of lesser tributaries into the main flow and a major crossroads of internal migration. Here in a continuous stream, bacteria and viruses released from our teeth meet those trapped in mucus from the sinuses and lungs and join the movement of nutritional energy toward the gut. These secretions, microbes, and food as well as anything on the food, are automatically swallowed and end up in the stomach via the esophagus. Like rafters on a river without oars, anything that enters the path of the GI tract has only one way to go: down and out the anus[3] with a few stops for processing along the way.

The stomach is one such stop. An acid lake, it is part quarantine and part consolidator of energy for further processing.  When we ingest solid food, it gets chomped down into something called chyme. Chyme is the mush you see in those rare moments when your digestive tract decides to reverse directions (why is it that the hotdog is always still whole?). While chyme is indeed food broken into small bits, our food needs to be broken down to even smaller pieces before the epithelial cells in our intestines can access the nutrients; therefore, the stomach serves the dual role as the first stop to continue that breakdown as well as a first attempt at eliminating anything that may damage the ecosystem. The presence of trypsin (an enzyme that breaks down proteins) and the high acidity of the stomach (pH 1.5-3.5) ensure that most living organisms don’t stay alive very long. In fact, scientists used to insist that the stomach was so acidic that no organism would survive let alone thrive—that it was the perfect barrier against any non-human elements invading our system. It wasn’t until Barry Marshall drank a flask of bacteria, causing rampant H. pylori growth in his stomach, that the community conceded that perhaps there are organisms that can live in GI ecological niches which surprise us[4]. Until recently, it was unknown if this particular species of bacteria played a role in human metabolism. Initial, correlative studies showed that people with H. pylori are less likely to develop throat cancer but more likely to develop stomach cancer[i]. However, we now know that H. pylori also serve as a key regulator of molecules (leptin and ghrelin) that control our feelings of feeling hungry and full[ii]. This scenario nicely illustrates that in ecological systems there are things that are neither good nor bad but are just different.

After a short soak in the acid lake, the gates of the stomach open onto the small intestine where our internal river speeds up its pace. When chyme (and any intrepid travelers) exits the stomach into the small intestine, other processes are triggered in our bodies. One of them is that the gallbladder begins to release bile acids that break down any fats in our nutrient flow. Bile acids play a role in our holobionts via modification by our microbial homesteaders. These acids, modified or not, join the flow over the surface of our small intestine which looks like a complexly folded and wrinkled shag carpet. Microscopic examination of living pieces of the small intestine show that it is a writhing surface of villi (the shag) with hair-like protrusions of microvilli (the fibers in the shag). These hairs upon hairs combined with the many folds give the 22-foot long small intestine a large surface. From a human perspective, all this surface area constitutes the most important part of the GI tract because of the epithelial cells’ (aka skin cells that make up the intestinal wall) active absorption of nutrients coming from the stomach. However, we cannot underestimate the microbes and viruses hearty enough to make their home here.

To our eyes, the villi and microvilli structures look like carpet, but to a microbe looking for a home, these undulating structures offer shelter and firm purchase against the rapidly moving river of mucus and nutrients. Still, not much is known about those microbes that make their home here. Only a few studies have come out recently about the small intestine, and they have confirmed that our micro-bionts living there play a vital role in our holobiont. The difficulty in studying this section of our GI river valley leaves us still with more questions than answers[5]. What we do know about the non-human inhabitants in the small intestine is that they rarely have physical contact with human cells[6]. One of the reasons for this isolation is that there is a physical barrier—a two-layer mucus zone—that keeps microbes, harmful or otherwise, removed from untoward contact with our cells. This mucus zone also continues into the large intestine, constituting the soft banks and bottom of our internal river. The mucus layer provides the ground (albeit a shifting one) that our gut inhabitants use to build their homes and cities. While the term “mucus layer” conjures up images of snot for most of us, for exploratory microbes looking for a home, it is rocky landscape, pocked and ridged with molecules that they can use to attach their homes or even eat. Most of our micro-bionts conduct their everyday business in or attached to the mucus layer.

[1] Antony Leuwenhoek was obsessed with investigating the hidden world going as far as coitus interuptus with his wife so that he could observe the “animalcules” in his semen without committing the sin of masturbation.
[2] A person with a permanent hole in their gut that allows outside access to the internal structure. The most famous fistulated human is Alexis St. Martin who was gut shot with a shotgun and healed with a permanent open hole. William Beaumont performed many digestive experiments on St. Martin’s exposed stomach that led to many insights into human digestive tract. St. Martin was not enthusiastic about these experiments.
[3] With the unforgettable exceptions of vomiting and reflux.
[4] Concessions that continue today. A recent paper outlines a microbial population in an African Hazda hunter-gatherer community that resembles that of a Western individual who suffers from Crohn’s Disease. But the Hazda are perfectly healthy! (Stephanie L. Schnorr et al., “Gut Microbiome of the Hadza Hunter-Gatherers,” Nature Communications 5 (April 15, 2014), doi:10.1038/ncomms4654.)
[5] What we do know quite a bit about the human structures and functions in this region. The villi of the small intestine have a cellular organization designed both to help absorb nutrients from ingested food at the top of each structure and to form an impervious protective wall against any harmful organism. At the base of the villi are deep recesses between each other called crypts.  Stems cells reside inside these crypts and continually divide to make new cells. These new cells migrate up the sides of the villi to become epithelial cells at the surface, replacing those cells lost in the harsh conditions of digestion. Some of the new cells will also differentiate into mucus-secreting goblet cells or hormone-secreting endocrine cells. In addition to the cells that leave the crypt, stem cells also make Paneth cells, which secrete antimicrobial peptides (defensins) and lysozyme granules to kill invading microbes. This protects the crypts from any pathogens, despite the billions of microbes located only a millimeter away.
[6] But as any long distance lovers will tell you, physical contact is not necessary to have a lot of impact on someone you are talking to.
“The Gastrointestinal Sourcebook by Rosenthal, Sara, M;Rosenthal, M., Sara: Lowell House 9780737300819 – DotCom Liquidators / DC 1,” accessed April 30, 2014, http://www.abebooks.com/servlet/BookDetailsPL?bi=1382701733&searchurl=ds%3D30%26isbn%3D9780737300819%26n%3D100121501%26sortby%3D17.
[i]“The Dr. Who Drank Infectious Broth, Gave Himself an Ulcer, and Solved a Medical Mystery | DiscoverMagazine.com,” Discover Magazine, accessed April 26, 2013, http://discovermagazine.com/2010/mar/07-dr-drank-broth-gave-ulcer-solved-medical-mystery#.UXracMrTw2E.
[ii] Yu Chen and Martin J. Blaser, “Association Between Gastric Helicobacter Pylori Colonization and Glycated Hemoglobin Levels,” Journal of Infectious Diseases 205, no. 8 (April 15, 2012): 1195–1202, doi:10.1093/infdis/jis106.
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