Human-associated microbial communities have adapted to environmental pressures. Doses of antibiotics select for a community with increased antibiotic resistance, inflammation is accompanied by expansion of community members equipped to flourish in the presence of immune effectors and Western diets shift the microbiota away from fibre degraders in favour of species that thrive on mucus. Recent data suggest that the microbiota of industrialized societies differs substantially from the recent ancestral microbiota of humans. Rapid modernization, including medical practices and dietary changes, is causing progressive deterioration of the microbiota, and we hypothesize that this may contribute to various diseases prevalent in industrialized societies. In this Opinion article, we explore whether individuals in the industrialized world may be harbouring a microbial community that, while compatible with our environment, is now incompatible with our human biology.
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Sonnenburg, J. L. & Backhed, F. Diet-microbiota interactions as moderators of human metabolism. Nature 535, 56–64 (2016).
Sommer, F. & Backhed, F. The gut microbiota — masters of host development and physiology. Nat. Rev. Microbiol. 11, 227–238 (2013).
Mayer, E. A., Knight, R., Mazmanian, S. K., Cryan, J. F. & Tillisch, K. Gut microbes and the brain: paradigm shift in neuroscience. J. Neurosci. 34, 15490–15496 (2014).
Donia, M. S. & Fischbach, M. A. Small molecules from the human microbiota. Science 349, 1254766 (2015).
Cryan, J. F. & Dinan, T. G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 13, 701–712 (2012).
Hooper, L. V., Littman, D. R. & Macpherson, A. J. Interactions between the microbiota and the immune system. Science 336, 1268–1273 (2012).
Moeller, A. H. et al. Cospeciation of gut microbiota with hominids. Science 353, 380–382 (2016).
Martinez, I. et al. The gut microbiota of rural papua new guineans: composition, diversity patterns, and ecological processes. Cell Rep. 11, 527–538 (2015).
Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012).
Clemente, J. C. et al. The microbiome of uncontacted Amerindians. Sci. Adv. 1, e1500183 (2015).
Mueller, N. T., Bakacs, E., Combellick, J., Grigoryan, Z. & Dominguez-Bello, M. G. The infant microbiome development: mom matters. Trends Mol. Med. 21, 109–117 (2015).
Modi, S. R., Collins, J. J. & Relman, D. A. Antibiotics and the gut microbiota. J. Clin. Invest. 124, 4212–4218 (2014).
Blaser, M. J. The theory of disappearing microbiota and the epidemics of chronic diseases. Nat. Rev. Immunol. 17, 461–463 (2017).
Tropini, C. et al. Transient osmotic perturbation causes long-term alteration to the gut microbiota. Cell 173, 1742–1754 (2018).
Smits, S. A. et al. Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania. Science 357, 802–806 (2017).
Sonnenburg, E. D. & Sonnenburg, J. L. Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell Metab. 20, 779–786 (2014).
Villmoare, B. et al. Early homo at 2.8 Ma from Ledi-Geraru, Afar, Ethiopia. Science 347, 1352–1355 (2015).
Hublin, J. J. et al. New fossils from Jebel Irhoud, Morocco and the pan-African origin of Homo sapiens. Nature 546, 289–292 (2017).
Richter, D. et al. The age of the hominin fossils from Jebel Irhoud, Morocco, and the origins of the Middle Stone Age. Nature 546, 293–296 (2017).
Fuller, D. Q. et al. Convergent evolution and parallelism in plant domestication revealed by an expanding archaeological record. Proc. Natl Acad. Sci. USA 111, 6147–6152 (2014).
David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).
Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011).
Shepherd, E. S., DeLoache, W. C., Pruss, K. M., Whitaker, W. R. & Sonnenburg, J. L. An exclusive metabolic niche enables strain engraftment in the gut microbiota. Nature 557, 434–438 (2018).
Chassaing, B. et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 519, 92–96 (2015).
Collins, J. et al. Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature 553, 291–294 (2018).
Suez, J. et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181–186 (2014).
Sonnenburg, E. D. et al. Diet-induced extinctions in the gut microbiota compound over generations. Nature 529, 212–215 (2016).
Backhed, F. et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17, 690–703 (2015).
Bokulich, N. A. et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci. Transl Med. 8, 343ra82 (2016).
Dethlefsen, L. & Relman, D. A. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4554–4561 (2011).
Miyoshi, J. et al. Peripartum antibiotics promote gut dysbiosis, loss of immune tolerance, and inflammatory bowel disease in genetically prone offspring. Cell Rep. 20, 491–504 (2017).
Schulfer, A. F., Battaglia, T., Alvarez, Y. & Bijnens, L. Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice. Nat Microbiol. 3, 234–242 (2018).
De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl Acad. Sci. USA 107, 14691–14696 (2010).
Ayeni, F. A. et al. Infant and adult gut microbiome and metabolome in rural Bassa and urban settlers from Nigeria. Cell Rep. 23, 3056–3067 (2018).
Tito, R. Y. et al. Insights from characterizing extinct human gut microbiomes. PLOS ONE 7, e51146 (2012).
Tito, R. Y. et al. Phylotyping and functional analysis of two ancient human microbiomes. PLOS ONE 3, e3703 (2008).
Cano, R. J. et al. Sequence analysis of bacterial DNA in the colon and stomach of the Tyrolean Iceman. Am. J. Phys. Anthropol. 112, 297–309 (2000).
Ochman, H. et al. Evolutionary relationships of wild hominids recapitulated by gut microbial communities. PLOS Biol. 8, e1000546 (2010).
Moeller, A. H. et al. Rapid changes in the gut microbiome during human evolution. Proc. Natl Acad. Sci. USA 111, 16431–16435 (2014).
Obregon-Tito, A. J. et al. Subsistence strategies in traditional societies distinguish gut microbiomes. Nat. Commun. 6, 6505 (2015).
Suzuki, T. A. & Worobey, M. Geographical variation of human gut microbial composition. Biol. Lett. 10, 20131037 (2014).
Schnorr, S. L. et al. Gut microbiome of the Hadza hunter-gatherers. Nat. Commun. 5, 3654 (2014).
Vangay, P. et al. US immigration westernizes the human gut microbiome. Cell 175, 962–972 (2018).
Ley, R. E. Prevotella in the gut: choose carefully. Nat. Rev. Gastroenterol. Hepatol. 13, 69–70 (2016).
Kovatcheva-Datchary, P. et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab. 22, 971–982 (2015).
Scher, J. U. et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2, e01202 (2013).
Fragiadakis, G. K. et al. Links between environment, diet, and the hunter-gatherer microbiome. Gut Microbes https://doi.org/10.1080/19490976.2018.1494103 (2018).
Jha, A. R. et al. Gut microbiome transition across a lifestyle gradient in Himalaya. PLOS Biol. 16, e2005396 (2018).
He, Y. et al. Regional variation limits applications of healthy gut microbiome reference ranges and disease models. Nat. Med. 24, 1532–1535 (2018).
Deschasaux, M. et al. Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography. Nat. Med. 24, 1526–1531 (2018).
Consortium, H. M. P. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).
Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).
Anderson, G. & Horvath, J. The growing burden of chronic disease in America. Public Health Rep. 119, 263–270 (2004).
Pawelec, G., Goldeck, D. & Derhovanessian, E. Inflammation, ageing and chronic disease. Curr. Opin. Immunol. 29, 23–28 (2014).
Lozano, R. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2095–2128 (2012).
Xu, J., Murphy, S. L., Kochanek, K. D. & Arias, E. Mortality in the United States, 2015. CDC https://www.cdc.gov/nchs/data/databriefs/db267.pdf (2016).
Organization, W. H. Global Health Observatory (GHO) data: life expectancy. WHO https://www.who.int/gho/mortality_burden_disease/life_tables/situation_trends_text/en/ (2019).
Gurven, M. & Kaplan, H. Longevity among hunter-gatherers: a cross-cultural examination. Popul. Dev. Rev. 33, 321–365 (2007).
Eaton, S. B., Konner, M. & Shostak, M. Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective. Am. J. Med. 84, 739–749 (1988).
Go, A. S. et al. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation 127, e6–e245 (2013).
Mozaffarian, D. et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation 131, e29–e322 (2015).
Agmon-Levin, N., Lian, Z. & Shoenfeld, Y. Explosion of autoimmune diseases and the mosaic of old and novel factors. Cell. Mol. Immunol. 8, 189–192 (2011).
Backhed, F., Manchester, J. K., Semenkovich, C. F. & Gordon, J. I. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc. Natl Acad. Sci. USA 104, 979–984 (2007).
Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).
Cox, L. M. et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158, 705–721 (2014).
Koeth, R. A. et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19, 576–585 (2013).
Feehley, T. et al. Healthy infants harbor intestinal bacteria that protect against food allergy. Nat. Med. 25, 448–453 (2019).
Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463 (2013).
Raichlen, D. A. et al. Physical activity patterns and biomarkers of cardiovascular disease risk in hunter-gatherers. Am. J. Hum. Biol. 29, e22919 (2016).
Caballero, B. The global epidemic of obesity: an overview. Epidemiol. Rev. 29, 1–5 (2007).
O’Keefe, S. J., Li, J. V. & Lahti, L. Fat, fibre and cancer risk in African Americans and rural Africans. Nat. Commun. 6, 6342 (2015).
Furman, D. & Davis, M. M. New approaches to understanding the immune response to vaccination and infection. Vaccine 33, 5271–5281 (2015).
Deehan, E. C. & Walter, J. The fiber gap and the disappearing gut microbiome: implications for human nutrition. Trends Endocrinol. Metab. 27, 239–242 (2016).
Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013).
Trompette, A. et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20, 159–166 (2014).
Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T cell generation. Nature 504, 451–455 (2013).
Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).
De Vadder, F. et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 84–96 (2014).
Lee, R. B. in Man the Hunter (eds Lee, B., DeVore, I. & Nash, J.) 30–48 (Aldine Publishing Company, 1968).
Poulain, M. et al. Identification of a geographic area characterized by extreme longevity in the Sardinia island: the AKEA study. Exp. Gerontol. 39, 1423–1429 (2004).
Yang, Y., Zhao, L. G., Wu, Q. J., Ma, X. & Xiang, Y. B. Association between dietary fiber and lower risk of all-cause mortality: a meta-analysis of cohort studies. Am. J. Epidemiol. 181, 83–91 (2015).
Kim, Y. & Je, Y. Dietary fiber intake and total mortality: a meta-analysis of prospective cohort studies. Am. J. Epidemiol. 180, 565–573 (2014).
Zeevi, D. et al. Personalized nutrition by prediction of glycemic responses. Cell 163, 1079–1094 (2015).
Sofi, F., Abbate, R., Gensini, G. F. & Casini, A. Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. Am. J. Clin. Nutr. 92, 1189–1196 (2010).
Pes, G. M. et al. Male longevity in Sardinia, a review of historical sources supporting a causal link with dietary factors. Eur. J. Clin. Nutr. 69, 411–418 (2015).
Dehghan, M. et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. Lancet 390, 2050–2062 (2017).
Marlowe, F. W. & Berbesque, J. C. Tubers as fallback foods and their impact on Hadza hunter-gatherers. Am. J. Phys. Anthropol. 140, 751–758 (2009).
Bello, M. G. D., Knight, R., Gilbert, J. A. & Blaser, M. J. Preserving microbial diversity. Science 362, 33–34 (2018).
Claw, K. G. et al. A framework for enhancing ethical genomic research with Indigenous communities. Nat. Commun. 9, 2957 (2018).
van Nood, E. et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368, 407–415 (2013).
Blaser, M. J. Antibiotic use and its consequences for the normal microbiome. Science 352, 544–545 (2016).
Okada, H., Kuhn, C., Feillet, H. & Bach, J. F. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clin. Exp. Immunol. 160, 1–9 (2010).
McGarvey, S. T. The thrifty gene concept and adiposity studies in biological anthropology. J. Polyn. Soc. 103, 29–42 (1994).
Brinkworth, J. F. & Barreiro, L. B. The contribution of natural selection to present-day susceptibility to chronic inflammatory and autoimmune disease. Curr. Opin. Immunol. 31, 66–78 (2014).
Nature Reviews Microbiology thanks R. Carmody and the other anonymous reviewer(s) for their contribution to the peer review of this work.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Sonnenburg, E.D., Sonnenburg, J.L. The ancestral and industrialized gut microbiota and implications for human health. Nat Rev Microbiol 17, 383–390 (2019). https://doi.org/10.1038/s41579-019-0191-8
Environmental Microbiology (2021)
Frontiers in Genetics (2021)
Journal of Orthopaedic Research (2021)
Pediatric Research (2021)
npj Biofilms and Microbiomes (2021)