|
|
REVIEW ARTICLE |
|
Year : 2017 | Volume
: 2
| Issue : 1 | Page : 5-8 |
|
Human microbiome and environmental disease
Gary Zhang1, Henry H Heng2
1 Salem High School, Plymouth-Canton Educational Park, Canton, MI 48187, USA 2 Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA
Date of Submission | 02-Mar-2017 |
Date of Acceptance | 28-Mar-2017 |
Date of Web Publication | 19-Apr-2017 |
Correspondence Address: Gary Zhang Salem High School, Plymouth-Canton Educational Park, 8400 Beck Rd, Canton, MI 48187 USA Henry H Heng Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 USA
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ed.ed_6_17
The importance of human microbiota and their genomes, human microbiome, in health and disease has been increasingly recognized. Human microbiome has tremendous impact in our pathophysiology by modulating metabolic functions, protecting against pathogens, and educating the immune system. In particular, human microbiome is a major player at the interface between humans and their environment and therefore is crucial to the development of environmental disease. In this article, we briefly summarize and interpret the recent advances in the understanding of the roles of human microbiome in environment-related health and disease, and call for a more systematic integration of human microbiome and environmental disease research within the framework of evolutionary medicine. Keywords: Environmental disease, fuzzy inheritance, human genome, human microbiome, microbiota, modern human disease
How to cite this article: Zhang G, Heng HH. Human microbiome and environmental disease. Environ Dis 2017;2:5-8 |
Introduction | |  |
In recent years, biomedical research revealed that the human body is host to around 100 trillion microbes that resides on or within a number of tissues and biofluids, including the skin, placenta, seminal fluid, uterus, lung, saliva, mucosa, and gastrointestinal tracts.[1] We have more microorganisms than we have our own human cells, which are outnumbered by approximately 3-1.[2] Types of microbiota include bacteria, archaea, fungi, and viruses. Bacterial cells and genes are as part of the body. In another word, humans are not single organisms, but superorganisms made up of lots of microbiota working together. Human microbiota and their genome, microbiome, are crucial to health and disease, particularly with respect to their roles in maintaining immune functions, aiding in food digestion, and acting as defense systems against pathogens.[3],[4] Changes of microflora profiles and behaviors in human bodies are associated with human diseases, such as cardiovascular disease, metabolic disease, autoimmune disease, and cancer. To a large extent, human disease phenotypes are results of interactions among the human genome, microbiome, and the environment,[5] as diseases are genotype/environment-induced phenotypic variants that are not compatible with a current environment.[6]
Environmental challenges, such as pollutions (air, water, and food) and lifestyles, have profound impacts on human microbiome that are associated with the initiation and progression of the diseases.
Human Microbiome Is an Addition to the Human Genome | |  |
The human genome is the genetic blueprint of human biology. Human microbiome is composed of the microbes as well as their genes and genomes that live in the human body. The human microbiome has been increasingly recognized as an important source of genetic diversity, a disease modulator, and an essential component of immunity.[7] To emphasize the interaction and unity of human genome and microbiome, a term “hologenome” is used to describe the complex of the host and microbial genome.[8],[9] Microbiome is considered as a stable component of hologenome, and the traits encoded by microbiome may be beneficial, detrimental, or no consequence to the host. The definition of hologenome contributes to a precise understanding of genetic variations in human that could be attributed to the changes of microbiome [Figure 1]. The changes in micobiome can be acquired from environment or hosts through the changes in microbial abundance and vertical or horizontal gene transfers. The National Institutes of Health of the United States has initiated Human Microbiome Project (HMP) to sequence the genome of the human microbiota, particularly the microbiota that inhabit the skin, mouth, nose, digestive tract, and vagina, with the mission of generating resources enabling comprehensive characterization of the human microbiota and analysis of their roles in health and disease.[10] The following research efforts have been proposed for HMP: (1) developing a reference set of microbial genome sequences and preliminary characterization of the human microbiome, (2) elucidating the relationship between disease and changes in the human microbiome, (3) developing new technologies for computational analysis, (4) developing new tools for computational analysis, and (4) establishing data analysis and coordinating center.
Human Microbiome Interacts With Environmental Factors to Influence Human Pathophysiology | |  |
The interactions between human genomics, the microbiome, and the environment have significant impact in human pathophysiology [Figure 1]. The profile of human microbiome can be affected by many environmental factors, such as life styles, exercise, pollutions, and nutrients.[5],[11] For example, exercise and diets influence human gut microbial diversity and intestinal dysbiosis associated with liver diseases and metabolic dysfunction.[12],[13] Many modern lifestyles have negative impact in the microbiome. Physical inactivity, chronic stress, air and water pollutions, day-night shift work schedule, antibiotics and other drugs with antimicrobial activities, and highly processed diet can alter the functional microbiome.[14],[15] The host's pathophysiological conditions can also affect microbiota. Hyperimmunity with increased levels of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, or immunodeficiency can significantly affect the human microbiota composition.[16],[17] On the other hand, human microbiota has significant impact in human pathophysiology. Gut microbiota influences human intestinal function by promoting gut-associated tissue regeneration, motility, and reducing the permeability of gut epithelial cells.[18] Alterations in the microbiota composition affect host's metabolism, behavior, and stress responses.[19],[20],[21] In addition, microbiota can also influence host's vascular system, and nervous system by repressing synaptic connectivity and promoting anxiety-like behavior.[22],[23]
Translational Applications of Engineering Human Microbiome in Health and Disease | |  |
Human microbiome acts as the first line of defense against pathogens. Development of many diseases is associated with disturbance of microbiome in human body. The microbiome field has been increasingly reaching a real translational discipline.[24] Microbiome-based medical treatments and applications are emerging. An important application of microbiome is medical diagnosis. Predefined microbiome markers may be used for diagnosis of disease. In additionally, analysis of patient microbiome profile could guild therapy decision-making for particular diseases.[25] Precision or personalized medicine can be more effective by considering patient's microbiomes. Analyzing microbial compositions from patients' fecal and oral materials can reveal whether diseases shape the microbiome or vice versa.[24],[26] The related information may be critical to determine the causes where the microbiome creates disease susceptibilities or maintains chronic disease conditions. An important application of human microbiome is microbiota transfer therapy (MTT). A recent study suggested that MTT can improve the symptom of autism spectrum disorders (ASDs).[27] Although the causes of ASD were poorly understood, gut microbiota have been implicated because children with ASD are associated with abnormal gut bacteria and suffer gastrointestinal problems. A 2-week antibiotic treatment and a bowel cleanse followed by an extended fecal microbiota transplant treatment for 7–8 weeks led to an approximately 80% reduction of gastrointestinal symptoms of ASD, including significant improvements in constipation, diarrhea, indigestion, and abdominal pain.[27]
Challenges and Opportunities | |  |
Despite the excitement within this emerging field, many challenges remain. First, while the contribution of microbiota to disease phenotypes can be demonstrated in various model systems, it is much harder to illustrate the same contributions in individuals when there are more diverse factors involved. Second, there are limited quantitative studies to compare the real contribution of microbiota in the clinic (or even in model systems) when there are other factors involved, including genomic and developmental factors. Third, the highly diverse pattern of microbiota could simply reflects a local environmental difference (e.g., the food we eat, the local conditions); how would one separate out these other causative factors (after all, patients of any kind often represent the minority of the population in the same environments)? Fourth, it is known that microbiota dynamics are high, and that redistribution can be quickly achieved, so how would one avoid the unexpected emergence of the initial treatment? Clearly, microbiota research will provide additional important knowledge of human diseases, but will not become a new magic bullet. New ideas are thus needed in this field to integrate microbiota with the human genome rather than with individual genes, as the human genome represents a genomic package for evolutionary selection,[28],[29] and the coexisting microgenomes act as another layer to modify genetic information. Such a realization further supports the concept that overall genome instability is a common basis for many diseases.[6] Most importantly, the concepts of adaptive systems and evolutionary medicine should be used in this field,[30] and the interaction of the human genome and microgenomes are only meaningful in the context of somatic cell evolution, because fundamentally, all genomic-environmental interactions can be considered as system-stress responses, which not only represents an evolutionary trade-off but also contributes to increased fuzzy inheritance.[31],[32]
The microbiota plays major roles in human health and disease. As an important addition to the human genome, microbiome is critically involved in human pathophysiology. The increasing environmental challenges and the interactions between environmental factors, human host, and microbiota implicate that human microbiome is a critical concept of research in environmental diseases. Although the application of microbiome in diagnostic and precision medicine is still in its early stage, it shows a promising future in treating modern human common disease, particularly those that are associated with environmental factors. The growing recognition of the physiological significance of human microbiome in environmental diseases and its potential applications in disease diagnosis and therapy projects that human microbiome is a hot biomedical research topic in the future, and the concept of evolutionary medicine will further advance this exciting field.
Acknowledgment
Gary Zhang is a high school student at the Salem High School of Michigan who was a summer student research volunteer with Professor Henry Heng at the Wayne State University School of Medicine.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References | |  |
1. | Ursell LK, Metcalf JL, Parfrey LW, Knight R. Defining the human microbiome. Nutr Rev 2012;70 Suppl 1:S38-44. |
2. | Sender R, Fuchs S, Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 2016;164:337-40. |
3. | Flint HJ, Scott KP, Louis P, Duncan SH. The role of the gut microbiota in nutrition and health. Nat Rev Gastroenterol Hepatol 2012;9:577-89. |
4. | Bäckhed F, Fraser CM, Ringel Y, Sanders ME, Sartor RB, Sherman PM, et al. Defining a healthy human gut microbiome: Current concepts, future directions, and clinical applications. Cell Host Microbe 2012;12:611-22. |
5. | Cho I, Blaser MJ. The human microbiome: At the interface of health and disease. Nat Rev Genet 2012;13:260-70. |
6. | Heng H, Regan S, Ye C. Genotype, environment, and evolutionary mechanism of diseases. Environ Dis 2016;1:14-23. [Full text] |
7. | Grice EA, Segre JA. The human microbiome: Our second genome. Annu Rev Genomics Hum Genet 2012;13:151-70. |
8. | Voss JD, Leon JC, Dhurandhar NV, Robb FT. Pawnobiome: Manipulation of the hologenome within one host generation and beyond. Front Microbiol 2015;6:697. |
9. | Theis KR, Dheilly NM, Klassen JL, Brucker RM, Baines JF, Bosch TC, et al. Getting the hologenome concept right: An eco-evolutionary framework for hosts and their microbiomes. mSystems 2016;1. pii: E00028-16. |
10. | NIH/National Human Genome Research Institute. “Human microbiome project: Diversity of human microbes greater than previously predicted.” ScienceDaily. ScienceDaily. Available from :www.sciencedaily.com/releases/2010/05/100520141214.htm. [Last accessed on 2010 May 21]. |
11. | Zhang K. Environmental diseases. Environ Dis 2016;1:1-2. [Full text] |
12. | Clarke SF, Murphy EF, O'Sullivan O, Lucey AJ, Humphreys M, Hogan A, et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 2014;63:1913-20. |
13. | Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 2014;146:1513-24. |
14. | Salvucci E. Microbiome, holobiont and the net of life. Crit Rev Microbiol 2016;42:485-94. |
15. | Conlon MA, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients 2014;7:17-44. |
16. | Fujimura KE, Lynch SV. Microbiota in allergy and asthma and the emerging relationship with the gut microbiome. Cell Host Microbe 2015;17:592-602. |
17. | Monaco CL, Gootenberg DB, Zhao G, Handley SA, Ghebremichael MS, Lim ES, et al. Altered virome and bacterial microbiome in human immunodeficiency virus-associated acquired immunodeficiency syndrome. Cell Host Microbe 2016;19:311-22. |
18. | Sommer F, Bäckhed F. The gut microbiota – Masters of host development and physiology. Nat Rev Microbiol 2013;11:227-38. |
19. | Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006;444:1027-31. |
20. | Diaz Heijtz R, Wang S, Anuar F, Qian Y, Björkholm B, Samuelsson A, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A 2011;108:3047-52. |
21. | Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004;118:229-41. |
22. | Stappenbeck TS, Hooper LV, Gordon JI. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci U S A 2002;99:15451-5. |
23. | Bercik P, Denou E, Collins J, Jackson W, Lu J, Jury J, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 2011;141:599-609, 609.e1-3. |
24. | Shukla SK, Murali NS, Brilliant MH. Personalized medicine going precise: From genomics to microbiomics. Trends Mol Med 2015;21:461-2. |
25. | Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Proteomics. Tissue-based map of the human proteome. Science 2015;347:1260419. |
26. | Kolmeder CA, Salojärvi J, Ritari J, de Been M, Raes J, Falony G, et al. Faecal metaproteomic analysis reveals a personalized and stable functional microbiome and limited effects of a probiotic intervention in adults. PLoS One 2016;11:e0153294. |
27. | Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, et al. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: An open-label study. Microbiome 2017;5:10. |
28. | Heng HH. The genome-centric concept: Resynthesis of evolutionary theory. Bioessays 2009;31:512-25. |
29. | Heng HH. Debating Cancer: The Paradox in Cancer Research. Hackensack, NJ: World Scientific; 2015. |
30. | Nesse RM, Ganten D, Gregory TR, Omenn GS. Evolutionary molecular medicine. J Mol Med (Berl) 2012;90:509-22. |
31. | Horne SD, Chowdhury SK, Heng HH. Stress, genomic adaptation, and the evolutionary trade-off. Front Genet 2014;5:92. |
32. | Horne SD, Ye CJ, Heng HH. Chromosomal Instability (CIN) in Cancer. In: eLS. Chichester: John Wiley & Sons, Ltd. 2015. |
[Figure 1]
|