The microbiome is a dynamic ecosystem, even more so than the ecosystem surrounding us in the outside world. The microbiome can change its character within hours and days versus years and decades in the external environment. Abundance and dominance of different species can shift with the food we eat, the drugs we take, or with our health status. As we age, the microbiome of childhood shifts dramatically; it can become richer and more complex with disease, injury, and travel and with long-term changes to diet and our immune systems.
This exposure to more and different bacteria as we age and travel is very likely a good experience for our microbiome. And it isn’t just age that determines the microbiome, the geographic regions of the world have a strong influence that is related to different cuisines and ethnicities.[i] People living in more traditional styles, such as Africa and South America, have different gut microbes and greater microbial diversity than people in the United States and other highly technological and urbanized places and this is likely related to the kinds of food each group eats.
A number of important questions remain. What determines the movement of bacteria in and out of our bodies? Do we have any control of the stability and composition of the microbiota in our gut? Are there cyclical patterns to the changes in composition? How is the internal ecosystem related to the external ecosystem or is it just a matter of the quality of the inputs (food and drugs) that we feed to the microbiome?
First off, bacteria are literally everywhere. Because bacteria break down organic molecule to obtain energy and nutrients, they can exist wherever there are organic molecules. The oceans are literally bacterial soup with billions of cells per cubic centimeter; bacteria in soils are similarly diverse and abundant. Although our main concerns as humans are typically about pathogenic bacteria, only a tiny fraction of bacteria interact with humans and most of them are mutualistic or commensal. That is, they live with us or on us, but rarely in a negative way. This is just as true of the microbiome. There are perhaps 10,000 species of bacteria in the human microbiome, but only a very small number are pathogenic and many of those are pathogenic only under certain conditions.
As wonderful as our digestive system is, it mainly breaks down the basic molecules of carbohydrates, proteins, and fats. Amylases break down starch to sugars and we have a number of enzymes to reduce complex sugars to simple sugars, which are then absorbed into the blood from the small intestine. We initiate protein digestion in the stomach and proteases complete the reduction of protein to amino acids in the small intestine. Fats are emulsified by bile salts from the gall bladder and reduced by lipases to fatty acids that can be absorbed into the lymph system through the small intestine. However, more complex molecules, especially those that require more time for reduction to smaller units, usually pass through the small intestine relatively unscathed.
The substances arriving in the large intestine are food for the bacteria, but what does that do for us? The role of bacteria in the colon, for the most part, is one of fermentation of sugars, which is the breaking down of complex sugars (polysaccharides) to lactic acid (lactate) to release a small amount of energy that the bacteria can then use. This activity takes place in an anaerobic environment (one that is lacking oxygen) which is the biochemical reason such a small amount of the available energy can be obtained. And the bacteria are capturing that energy, not us.
For the most part, the human large intestine is not capable of absorbing nutrients and much of what the bacteria produce is of little use to us. However, bacterial fermentation produces acetate, propionate, and butyrate which are metabolic end-products and they are involved in stimulating the human immune system.
These three short-chain fatty acids are consumed by cells lining the gut and enhance their protective functions. The proportion of acetate to propionate also seems to be related to reduced inflammation and both chemicals interact in different ways with the function of certain vitamins, some of which are produced in the colon.
Admittedly, the production of vitamins and other useful compounds may be correlated to the presence of gut bacteria and may not necessarily represent a symbiotic connection. However, as the gut fauna diversity develops, bacteria begin to occupy the mucus lining of the digestive tract and this has been shown to have a protective function and is definitely mutualistic. In particular, the presence of our normal gut microbes in the mucus lining of the colon prevents the colonization of pathogenic bacteria and resultant infections.[ii]
One implication of this role of bacteria is that individuals, such as malnourished children and those regularly using antibiotics, have less diverse gut communities and may have a reduced ability to resist infections.[iii] In general, it appears that our intestinal microbiota may be linked to the reduction, incidence, or severity of a large number of digestive disorders.[iv] Of particular importance are the new discoveries tentatively linking a compromised microbiome in infants (often through the use of antibiotics) with a number of developmental conditions and immunological abnormalities in children. [v]
Overall, it seems that the health of our internal system can be a condition of too few or too many, which is to say that it isn’t just the diversity of the gut ecosystem, but the relative abundances of the different species. Greater diversity provides for greater range of function and provides our system with necessary nutrients. But greater abundance can be too much of a good thing by creating imbalances.
So, what physical or physiological filters act to control, reduce, or limit the diversity of the gut fauna? The first strong filter is the stomach and the acid environment found there.[vi] Very few microbes can survive passage through the stomach and this greatly reduces pathogenic bacteria from reaching more sensitive structures such as the small and large intestines. This filter is incredibly important to our health and protection from the bacteria in and on our food.
The initial colonization of the lower digestive tract began at birth as the microbiome of the mother colonized the baby via mother’s milk and close physical contact.[vii] An infant’s stomach and digestive system is immature and the mother’s contribution to the infant’s microbiome is able to pass through the stomach safely. Recent research provides strong evidence that a healthy maternal microbiome supports a healthy infant microbiome.
As adults, we have accumulated a diverse microbiome through regular contact with the environment around us. Certainly, the food we eat and other forms of contact with the microbial world will have contributed new species to our personal microbiome. However, it is important to remember that the general environment of the lower gut is anaerobic, it lacks oxygen, because the bacterial community consumes all of the available oxygen as it breaks down organic molecules. Only bacteria that can tolerate low oxygen environments can persist and thrive there.
If this is the case, how do new species of bacteria move from the external and aerobic environment to the internal and anaerobic environment of the large intestine? How does diversity increase if the one of the filters to entrance is the environment itself? This is an understudied aspect of the microbiome. If the environmental filter is sufficiently strong, then we could suspect that the microbiome we acquire in childhood is essentially the basic microbiome we possess for the rest of our lives. However, as the anaerobic bacteria are excreted from the human body in feces, transfer to new hosts can easily occur.
This probably facilitated by characteristic of the different bacteria. Many species produce reproductive units (such as cysts) that can tolerate very hostile conditions and some bacteria can tolerate both aerobic and anaerobic conditions. This allows them to move from the mouth, through the digestive system, to the colon unscathed. Because of this, it is very likely that children playing together represent a suitable environment for transfer of the microbial community among individuals and all close social groups will tend to share microbes.
We also know that the food we eat carries a wide range of microbial hitchhikers that enter our bodies even if they don’t make it past the filters. Some types of food may be more suitable for transferring passengers to the digestive system and some passengers of some food types may be more resistant to the acidic conditions of the stomach.
Dietary probiotics are marketed as a mechanism for delivering beneficial microbes to the large intestine and the presumption is, of course, that they will survive the journey through the stomach. Probiotic foods are those that possess bacteria, such as yogurts, and these bacteria (especially lactobacilli) are beneficial because of their ability to break down molecules, such as lactose sugars, that can cause digestive distress for sensitive people. However, probiotic foods generally contain aerobic species and their survival in the anaerobic colon may be limited. Thus, at this point, we know very little about the food we eat and the movement of beneficial bacteria via that food.
There are occasions in life when the lower bowel is cleansed or nearly sterilized for one reason or another. Very strong antibiotics can greatly reduce the bacterial community as can bowel cleansing, for example, prior to a colonoscopy. Doctors and dieticians will often recommend dairy foods with live bacteria cultures for recolonizing the intestine, but this certainly comes nowhere near to re-establishing the diversity of the entire community. It is very likely that no matter how severe the sterilization process, it is highly unlikely that any bacterial species is ever 100% removed and the remaining individuals will quickly reestablish the population as soon as conditions return to normal. (Remember that one bacterium can produce a trillion descendants in 12 hours.).
Recent research also suggests that the “useless” and “vestigial” appendage known as the appendix may play a key role here. The appendix is a cul-de-sac that is home to a very high diversity of bacteria. Of course, when inflamed it can be dangerous, due to the threat of rupture and release of bacteria into the body cavity. Physically, it is somewhat isolated from activities of the lower colon and may act as a reservoir for re-establishing the normal bacterial community.[viii] Of course, the re-inoculation of the colon is dependent on the presence of the those bacteria in the colon prior to the sterilizing event and many people have had their appendix removed .
Currently, we are just beginning to appreciate the incredible complexity of the internal microbiome, its development, maintenance, health, and direct and indirect connections to other bodily functions. As with any biomedical research, the sample sizes we need for truly understanding how these complex processes affect and support humans as a species are rather immense because of the diversity among the human population itself. Between variables such as geography, ethnicity, cuisine, age, experience, early-childhood exposure, disease, gender, and lifestyle (to name but a few), it is difficult to make conclusive statements about the microbiome that apply to all people.
In truth, the particular microbiome you and I possess is, in fact, unique to each of us and a reflection of our personal histories. The microbiome is dynamic, influenced by the external environment, adapting and adjusting constantly, resistant and resilient, and works in very close harmony with the human system that surrounds it and sustains it.
The microbiome-human tandem is an intricate partnership.
[i] Yatsunenko, Tanya, Federico E. Rey, Mark J. Manary, Indi Trehan, Maria Gloria Dominguez-Bello, Monica Contreras, Magda Magris et al. (2012) "Human gut microbiome viewed across age and geography." Nature 486 (7402): 222-227. [ii] Sommer F, Bäckhed F (2013). "The gut microbiota—masters of host development and physiology". Nat Rev Microbiol. 11 (4): 227–38. doi:10.1038/nrmicro2974 [iii] Million, Matthieu; Diallo, Aldiouma; Raoult, Didier (2016). "Gut microbiota and malnutrition". Microbial Pathogenesis. doi:10.1016/j.micpath.2016.02.003 [iv] Guarner, F; Malagelada, J (2003). "Gut flora in health and disease". The Lancet. 361 (9356): 512–9. doi:10.1016/S0140-6736(03)12489-0. Shen S, Wong CH (2016). "Bugging inflammation: role of the gut microbiota". Clin Transl Immunology (Review). 5 (4): e72. doi:10.1038/cti.2016.12 [v] Martin Blaser “Missing Microbes” 2014. Picador [vi] DeAnna E. Beasley et al. 2015. The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome. PLoS ONE, July 2015 [vii] Ley, Ruth E., et al. "Obesity alters gut microbial ecology." Proceedings of the National Academy of Sciences of the United States of America 102.31 (2005): 11070-11075. [viii] R. Randal Bollinger, Andrew S. Barbas, Errol L. Bush, Shu S. Lin, William Parker. 2007. Biofilms in the large bowel suggest an apparent function of the human vermiform appendix. Journal of Theoretical Biology 249:826-831.
