J. Alcock et al Prospects& Overviews■■■■ discordance, or environmental mismatch, has been cited as changes drastically within 24 hours of changing diet [ 14, 1151 the source of"diseases of civilization, "including obesity, or administration of antibiotics [116]. Fecal transplants have cancer, and cardiovascular disease [105. Similar logic shown efficacy in treating a variety of diseases [117 The best postulates that past scarcity of calorie dense foods and approaches to managing our microbiota are still open critical micronutrients has also shaped modern food prefer. questions. Many studies of the effects of gut microbes on ences. The traditional diet of pre-agricultural humans relied health have focused on identifying individual taxa that are on low-carbohydrate plant foods and game, low in fat. Among responsible for human diseases, an approach that has been hunter gatherers, food acquisition efforts have been shown largely unsuccessful in generating predictive hypotheses to prioritize energy dense foods, gathered in a pattern that Studies have identified conflicting different groups of a maximizes energy capture relative to energy expenditure. microbes associated with various diseases, including obesi This strategy, described as optimal foraging theory, is fitness ty [118, 119 In other domains, it has proven useful to shift the enhancing in an environment where energy dense foods were level of analysis from properties of the individual to properties oL rare and hard to acquire [106 Under this hypothesis, in the of the population, e. g. diversity [120]. Until we have a better modern food environment with abundant food and sedentary understanding of the contributions and interactions between lifestyles, once-adaptive physiologic mechanisms regulating individual microbial taxa, it may be more effective to focus energy intake and expenditure have gone awry, leading to interventions on increasing microbial diversity in the gut. overeating and obesity Competition between genomes is likely to produce a Despite the intuitive appeal of this hypothesis, a number variety of conflicts, and we propose that one important area of food preferences and cravings are not in accord with its impacting human health, is in host eating behavior and predictions. For example, one of the most common modern nutrient acquisition. Genetic conflict between host and cravings involves a food that ancient hominids never knew microbiota selecting for microbes that manipulate host and which fulfills no nutritional requirement: chocolate [ 102]. eating behavior adds a new dimension to current view The hypothesis that environmental mismatch explains points, e.g. host-microbiota mutualism [11], that can explain diseases caused by diet has also been criticized by others mechanisms involved in obesity and related diseases as overly simplistic [86] Nutrient deprivation is not sufficient to explain The authors thank A. Boddy, A. Caulin, R. Datta, and M. unhealthy eating Fischbach as well as A. moore and the anonymous reviewers for helpful feedback, suggestions, and discussions. This work A similar hypothesis proposes that cravings result from was supported in part by the wissenschaftskolleg zu Berlin nutrient shortage [84]. For instance, fruit flies seek out specific (Institute for Advanced Study), a Research Scholar Grant nutrients after deprivation [107 However, this hypothesis #117209-RSG-09-163-01-CNE from the American Cancer Socie. does not explain many findings regarding cravings in humans. ty, the Bonnie J. Addario Lung Cancer Foundation, and NIH Food cravings strike even in times of plenty [108, 109 and grants F32 CA132450, PO1 CA91955, RO1 CA149566, Ro1 often foods that would satisfy a supposed nutrient shortage CA170595, and Ro1 CA140657 are not the ones that are craved [110. Furthermore fasting reduces cravings [111-113] rather than increasing them, as The authors have declared no conflict of interest. would be expected from the nutrient shortage hypothesis. The same pattern holds for cravings of non-food items such as clay and earth [114]. Young and colleagues subjected geophagy References (earth-eating) to a systematic review and concluded that human geophagy is not driven by nutrient scarcity [114] 1. Flegal KM, Carroll MD, ogden CL, Curtin LR. 2010. Prevalence and trends in obesity among US adults, 1999-2008. JAMA 303: 235-41 2. Calle EE, Kaaks R. 2004. Overweight, obesity and cancer: epidemio- Nat Rev Cancer 4: Conclusions Modern biology suggests that our bodies are composed of a omen. N Engl J Med 322: 882- diversity of organisms competing for nutritional resources. 4. Anderson Jw, Kendall Cw, Jenkins DJ. 2003. Importance of weight Evolutionary conflict between the host and microbiota may lead to cravings and cognitive conflict with regard to food n R, Aktipis CA. 2007. Modularity and the social mind choice. Exerting self-control over eating choices may be partly 6. Rhee SH, Pothoulakis C, Mayer EA. 2009. Principles and clinical a matter of suppressing microbial signals that originate in the ut. Acquired tastes may be due to the acquisition of microbes that benefit from those foods. Our review suggests that one Norris v, Molina F, Gewirtz AT 2013. Hypothesis: bacteria control host ay to change eating behavior is by intervening in our 8. Lyte M 2011. Probiotics function mechanistically as delivery vehicles microbiota for neuroactive compounds: microbial endocrinology in the design and It is encouraging that the microbiota can be changed by ays33574-81 nany interventions, hence facilitating translation to the clinic 9. Haig D. 2010. Transfers and transitions: parent-offspring conflict, and the evolution of human life history. Proc Nati and public health efforts. Microbiota community structure Acad Sci USA 107: 1731- 946 Bioessays 36: 940-949, C 2014 The Authors Bioessays published by WLEY Perodicals, Inc.discordance, or environmental mismatch, has been cited as the source of “diseases of civilization,” including obesity, cancer, and cardiovascular disease [105]. Similar logic postulates that past scarcity of calorie dense foods and critical micronutrients has also shaped modern food prefer￾ences. The traditional diet of pre-agricultural humans relied on low-carbohydrate plant foods and game, low in fat. Among hunter gatherers, food acquisition efforts have been shown to prioritize energy dense foods, gathered in a pattern that maximizes energy capture relative to energy expenditure. This strategy, described as optimal foraging theory, is fitness enhancing in an environment where energy dense foods were rare and hard to acquire [106]. Under this hypothesis, in the modern food environment with abundant food and sedentary lifestyles, once-adaptive physiologic mechanisms regulating energy intake and expenditure have gone awry, leading to overeating and obesity. Despite the intuitive appeal of this hypothesis, a number of food preferences and cravings are not in accord with its predictions. For example, one of the most common modern cravings involves a food that ancient hominids never knew and which fulfills no nutritional requirement: chocolate [102]. The hypothesis that environmental mismatch explains diseases caused by diet has also been criticized by others as overly simplistic [86]. Nutrient deprivation is not sufficient to explain unhealthy eating A similar hypothesis proposes that cravings result from nutrient shortage [84]. For instance, fruit flies seek out specific nutrients after deprivation [107]. However, this hypothesis does not explain many findings regarding cravings in humans. Food cravings strike even in times of plenty [108, 109], and often foods that would satisfy a supposed nutrient shortage are not the ones that are craved [110]. Furthermore, fasting reduces cravings [111–113] rather than increasing them, as would be expected from the nutrient shortage hypothesis. The same pattern holds for cravings of non-food items such as clay and earth [114]. Young and colleagues subjected geophagy (earth-eating) to a systematic review and concluded that human geophagy is not driven by nutrient scarcity [114]. Conclusions Modern biology suggests that our bodies are composed of a diversity of organisms competing for nutritional resources. Evolutionary conflict between the host and microbiota may lead to cravings and cognitive conflict with regard to food choice. Exerting self-control over eating choices may be partly a matter of suppressing microbial signals that originate in the gut. Acquired tastes may be due to the acquisition of microbes that benefit from those foods. Our review suggests that one way to change eating behavior is by intervening in our microbiota. It is encouraging that the microbiota can be changed by many interventions, hence facilitating translation to the clinic and public health efforts. Microbiota community structure changes drastically within 24 hours of changing diet [14, 115] or administration of antibiotics [116]. Fecal transplants have shown efficacy in treating a variety of diseases [117]. The best approaches to managing our microbiota are still open questions. Many studies of the effects of gut microbes on health have focused on identifying individual taxa that are responsible for human diseases, an approach that has been largely unsuccessful in generating predictive hypotheses. Studies have identified conflicting different groups of microbes associated with various diseases, including obesi￾ty [118, 119]. In other domains, it has proven useful to shift the level of analysis from properties of the individual to properties of the population, e.g. diversity [120]. Until we have a better understanding of the contributions and interactions between individual microbial taxa, it may be more effective to focus interventions on increasing microbial diversity in the gut. Competition between genomes is likely to produce a variety of conflicts, and we propose that one important area, impacting human health, is in host eating behavior and nutrient acquisition. Genetic conflict between host and microbiota – selecting for microbes that manipulate host eating behavior – adds a new dimension to current view￾points, e.g. host-microbiota mutualism [11], that can explain mechanisms involved in obesity and related diseases. Acknowledgements The authors thank A. Boddy, A. Caulin, R. Datta, and M. Fischbach as well as A. Moore and the anonymous reviewers for helpful feedback, suggestions, and discussions. This work was supported in part by the Wissenschaftskolleg zu Berlin (Institute for Advanced Study), a Research Scholar Grant #117209-RSG-09-163-01-CNE from the American Cancer Socie￾ty, the Bonnie J. Addario Lung Cancer Foundation, and NIH grants F32 CA132450, P01 CA91955, R01 CA149566, R01 CA170595, and R01 CA140657. The authors have declared no conflict of interest. References 1. Flegal KM, Carroll MD, Ogden CL, Curtin LR. 2010. Prevalence and trends in obesity among US adults,1999–2008. JAMA 303: 235–41. 2. Calle EE, Kaaks R. 2004. Overweight, obesity and cancer: epidemio￾logical evidence and proposed mechanisms. Nat Rev Cancer 4: 579–91. 3. Manson JE, Colditz GA, Stampfer MJ, Willett WC, et al. 1990. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med 322: 882–9. 4. Anderson JW, Kendall CW, Jenkins DJ. 2003. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. J Am Coll Nutr 22: 331–9. 5. Kurzban R, Aktipis CA. 2007. Modularity and the social mind: are psychologists too self-ish? Pers Soc Psychol Rev 11: 131–49. 6. Rhee SH, Pothoulakis C, Mayer EA. 2009. Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastro￾enterol Hepatol 6: 306–14. 7. Norris V, Molina F, Gewirtz AT. 2013. Hypothesis: bacteria control host appetites. J Bacteriol 195: 411–6. 8. Lyte M. 2011. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. BioEssays 33: 574–81. 9. Haig D. 2010. Transfers and transitions: parent-offspring conflict, genomic imprinting, and the evolution of human life history. Proc Natl Acad Sci USA 107: 1731–5. J. Alcock et al. Prospects & Overviews .... 946 Bioessays 36: 940–949,
2014 The Authors. Bioessays published by WILEY Periodicals, Inc. Review essays