By Bryan Peacker ’18

THURJ Staff

Microbiota, the bacteria that symbiotically reside in animals, are a critical part of every human’s physiology, leading scientists to call it “the forgotten organ” (O’Hara & Shanahan, 2006). Along with the multitude of different types of human cells that process food and aid in the absorption of nutrients, an even more diverse amalgam of microfauna reside in the gut. When the intestines fail irreversibly, surgeons resort to an entire intestinal transplant, replacing the entire gut with healthy intestines. But what if for certain diseases, instead of transplanting an entire gut, only the microfauna are transplanted? Could the intestines be healed again? It is this question that has motivated investigations into the microbiome.

These microfauna are not just found in the gastrointestinal tract, and not just in humans. They are found in all mammals on the skin, in the eyes, in the intestines, in the nose, and on hair. The types of microbes that can be found within and among species is highly variable, and in studies of the DNA sequences found in the microbiomes of mice and humans, scientists have discovered that 85% of the sequences obtained from a mouse are not found in humans (Ley et al., 2005). Considering that the human body contains about 1014 bacterial cells, and each human generation can host one million generations of bacterial divisions, the genetic diversity is unsurprising. There are even differences in microbial composition among different ethnic groups, and although identical twins have microbiomes that are highly related to each other, they are still different enough to suggest that after they are born, their microbiomes are altered (McNulty et al., 2011).

If individual microbiomes are so diverse, how could they possibly be used for potential treatments? The answer lies in the conservation of the core functions of the bacteria. Even though there are more than fifty different phyla of bacteria that have been identified residing in humans, most of the variation is caused a very small proportion of the total microbiome, and the majority of the microbiota in humans can be accounted for by about six phyla (Costello et al., 2009). The individual bacteria themselves compete within a human for key nutrients and molecules needed for their own survival, which leads to the evolution of bacteria that are more similar to each other, since the bacteria that have the best mechanisms for survival are likely to be similar (Cho & Blaser, 2012). Thus, as a result of this competition and the colossal amount of bacterial biomass inside the human body, many bacterial genes perform similar functions. Bacteria are incredibly resilient, meaning that they withstand disturbance, which is why they are able to continue to execute the mechanisms that they adapt. This adaptation has been demonstrated by a study in which patients ingested milk containing 108 bacteria of many different species. Despite ingesting this milk daily, after 7 weeks, the expression of genes from the original gut microbiota was found to be essentially unaffected, which has had important medical implications, since it explains why humans have been able to consume antibiotics without significant effects to the microbiome (McNulty et al., 2011).

When the microbiome’s composition is altered or when it is removed entirely, it can have catastrophic implications for a person’s health. Mostly, research on the microbiome has focused on correlations between the microbiota in the gut and different diseases. For instance, by testing for the types of bacteria present in the skin of psoriasis patients, it was found that in sick patients, Firmicutes are more abundant than normal and Actinobacteria are underrepresented (Gao, Tseng, Strober, Pei, & Blaser, et al. 2008). Other scientists have found different correlations, such as the increased abundance of Pseudomonadaceae in patients with chronic ulcers who are treated with antibiotics, and the increased abundance of Streptococcaceae in patients with diabetic ulcers (Cho & Blaser, 2012). A surprising finding is that in mice, without the presence of a specific type of segmented filamentous bacteria, immune cells in the lowest skin layer of mice cannot differentiate and perform their specific functions (Ivanov II et al., 2008).

So can certain medical conditions be treated by simply restoring the normal composition of microfauna present in a patient? Microfauna transplantation is not a distant dream; in fact, it is a reality that has already been utilized by researchers in attempts to treat diseases. When Clostridium difficile, a deadly bacterium, infects humans, it causes irritation to the lining of the intestines and can even cause a hole to be formed. Although this infection is usually treated with antibiotics, treatments with usual oral medication often does not work with one hundred percent efficacy, and the infection will recur with rates as high as 60% (Louie et al., 2011). In order to test whether or not the microfauna of a healthy individual could be transplanted to an infected patient, scientists took samples from the feces of healthy donors, isolated the bacteria present in the sample, and transferred them to capsules (Youngster et al., 2014). When the capsules were then administered to patients, the symptoms of 90% of the patients were resolved as a result of the healthy microbiota in the gut, acting as a testament to the possibility of the utilization of microbiota in the treatment of diseases.

This successful treatment has opened the door to a new perspective on human physiology. By taking a person’s microbiota into account, treatments can be optimized and doctors’ understanding of diseases can be improved. However, there are still limitations to the current tools that scientists use to study these microorganisms, such as the inability of current methods to explain the complexity of the data obtained from analyses of the genomes of these bacteria, which seem to be able to rapidly transfer genetic information to other microbial communities in the microbiome (Smillie et al., 2011). Scientists are in need of these better tools in order to be able to fully account for the correlations that are observed between different compositions of bacteria in different human diseases. However, with this newfound awareness, the potential of the study of this “forgotten organ” has finally been recognized, and previously unconsidered possibilities for treatments of disease now loom on the horizon.

 

References

Cho, I., Blaser, M.J. (2012). The Human Microbiome: at the interface of health and disease. Nature Reviews Genetics, 13(4), 260-270.

Costello E.K., Lauber, C.L., Hamady, M., Fierer, N., Gordon, J.I., Knight, R. (2009). Bacterial community variation in human body habitats across space and time. Science, 326(5960), 1694-1697.

Gao, Z., Tseng, C.H., Strober, B.E., Pei, Z., Blaser, M.J. (2008). Substantial alterations of the cutaneous bacterial biota in psoriatic lesions. PLoS ONE3(7), e2719.

Ivanov, I.I., Frutos, R.L., Manel, N., Yoshinaga, K., Rifkin, D.B., Sartor, R.B., Finlay, B.B, Littman, D.R. (2008). Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe, 4(4), 337–349.

Ley, R.E., Bäckhed, F., Turnbaugh, P., Lozupone, C.A., Knight, R.D., Gordon, J.I. (2005). Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences, 102, 11070–11075.

Louie, T.J., Miller, M.A., Mullane, K.M., Weiss, K., Lentnek, A., Golan, Y., Gorbach, S., Sears, P., and Shue, Y. (2011). Fidaxomicin vs vancomycin for Clostridium difficile infection. New England Journal of Medicine, 364(5), 422-431.

McNulty, N.P., Yatsunenko, T., Hsiao, A., Fiath, J.J., Muegge, B.D., Goodman, A.L., Henrissat, B., Oozeer, R., Cools-Portier, S., Gobert, G., Chervaux, C., Knights, D., Lozupone, C.A., Knight, R., Duncan, A.E., Bain, J.R., Muehlbauer, M.J., Newgard, C.B., Heath, A.C., and Gordon, J.I. (2011). The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins. Science Translational Medicine, 3(106), 106ra106.

O’Hara, A.M. and Shanahan, F. (2006). The gut flora as a forgotten organ. EMBO Reports, 7(7), 688–693.

Youngster, I., Russell, G.H., Pindar, C., Ziv-Baran, T., Sauk, J., Hohmann, E.L. (2014). Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection. Journal of the American Medical Association, 312(17), 1772-1778.

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