Prospects Overviews Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms Joe Alcock", Carlo C Maley/3/4*and C. Athena Aktip/s2)3) 4)5) Microbes in the gastrointestinal tract are under selective Introduction: Evolutionary conflict pressure to manipulate host eating behavior to increase their between host and microbes leads to fitness,sometimes at the expense of host fitness. Microbes host manipulation may do this through two potential strategies: generating cravings for foods that they specialize on or foods that The struggle to resist cravings for foods that are high in sugar suppress their competitors, or( inducing dysphoria until and fat is part of daily life for many people. Unhealthy eating is we eat foods that enhance their fitness. We review several a major contributor to health problems including obesity [1] as well as sleep apnea, diabetes, heart disease and cancer 2-4 potential mechanisms for microbial control over eating Despite negative effects on health and survival, unhealthy behavior including microbial influence on reward and satiety eating patterns are often difficult to change The resistance to pathways, production of toxins that alter mood, changes to change is frequently framed as a matter of"self-control, "and receptors including taste receptors and hijacking of the it has been suggested that multiple "selves"or cognitive vagus nerve, the neural axis between the gut and the brain. modules exist [51 each vying for control over our eating We also review the evidence for alternative explanations for behavior. Here, we suggest another possibility: that evolution ry conflict between host and microbes in the gut leads cravings and unhealthy eating behavior. Because microbiota microbes to divergent interests over host eating behavior.Gut are easily manipulatable by prebiotics, probiotics, anti- microbes may manipulate host eating behavior in ways that biotics,fecal transplants, and dietary changes, altering our promote their fitness at the expense of host fitness. Others microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating. behavior [6-8 though not in the context of competing fitness interests and evolutionary conflict Conflict over resource acquisition and resource allocation Keywords can occur as a result of conflict between different genetic cravings; evolutionary conflict; host manipulation; interests within an organism. For example, genetic conflict microbiome; microbiota; obesity between maternal and paternal genes is hypothesized to play a role in the unusual eating behavior that characterizes the childhood genetic diseases Beckwith-Wiedemann syndrome and Prader-Willi syndrome. These syndromes are character Dol10.1002/bies.201400071 ized by altered appetite and differences in infant suckling that can result from overexpression of genes of paternal Emergency Medicine University of New Mexico, or maternal origin, respectively [9, 10]. In parent-of-origin enter for Evolution and Cancer, Helen Diller Family Compr genetic conflict, paternally imprinted genes are thought to drive increased demands for extracting resources from tment of Surgery, University of California San Francisco, San the mother, and maternally imprinted genes tend to resist Francisco, CA, US Wissenschaftskolleg zu Berlin, (Institute for Advanced Study Berlin).Berlin, these effects. Metagenomic conflict between host and microbiome can be considered an extension of this genetic 6)Department of Psychology, Arizona State University, Tempe, AZ, USA conflict framework, but one that includes other genomes (i.e. microbes in the gut) with genes that affect the physiology and behavior of a host organism, potentially altering host eating E-mail: carlo. maley@ucsfmedctr. org, cmaley @ alum. mit. edu behavior in ways that benefit microbe fitness 940www.bioessays-journal.comBioessays36:940-949,@2014The pen access article under the terms distribution and reproduction in any m led the original work is properlyProspects & Overviews Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms Joe Alcock1), Carlo C. Maley2)3)4)
and C. Athena Aktipis2)3)4)5) Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness. Microbes may do this through two potential strategies: (i) generating cravings for foods that they specialize on or foods that suppress their competitors, or (ii) inducing dysphoria until we eat foods that enhance their fitness. We review several potential mechanisms for microbial control over eating behavior including microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review the evidence for alternative explanations for cravings and unhealthy eating behavior. Because microbiota are easily manipulatable by prebiotics, probiotics, anti￾biotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating. Keywords: .cravings; evolutionary conflict; host manipulation; microbiome; microbiota; obesity Introduction: Evolutionary conflict between host and microbes leads to host manipulation The struggle to resist cravings for foods that are high in sugar and fat is part of daily life for many people. Unhealthy eating is a major contributor to health problems including obesity [1] as well as sleep apnea, diabetes, heart disease, and cancer [2–4]. Despite negative effects on health and survival, unhealthy eating patterns are often difficult to change. The resistance to change is frequently framed as a matter of “self-control,” and it has been suggested that multiple “selves” or cognitive modules exist [5] each vying for control over our eating behavior. Here, we suggest another possibility: that evolution￾ary conflict between host and microbes in the gut leads microbes to divergent interests over host eating behavior. Gut microbes may manipulate host eating behavior in ways that promote their fitness at the expense of host fitness. Others have hypothesized that microbes may be affecting our eating behavior [6–8], though not in the context of competing fitness interests and evolutionary conflict. Conflict over resource acquisition and resource allocation can occur as a result of conflict between different genetic interests within an organism. For example, genetic conflict between maternal and paternal genes is hypothesized to play a role in the unusual eating behavior that characterizes the childhood genetic diseases Beckwith–Wiedemann syndrome and Prader–Willi syndrome. These syndromes are character￾ized by altered appetite and differences in infant suckling that can result from overexpression of genes of paternal or maternal origin, respectively [9, 10]. In parent-of-origin genetic conflict, paternally imprinted genes are thought to drive increased demands for extracting resources from the mother, and maternally imprinted genes tend to resist these effects. Metagenomic conflict between host and microbiome can be considered an extension of this genetic conflict framework, but one that includes other genomes (i.e., microbes in the gut) with genes that affect the physiology and behavior of a host organism, potentially altering host eating behavior in ways that benefit microbe fitness. DOI 10.1002/bies.201400071 1) Department of Emergency Medicine, University of New Mexico, Albuquerque, NM, USA 2) Center for Evolution and Cancer, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA 3) Department of Surgery, University of California San Francisco, San Francisco, CA, USA 4) Wissenschaftskolleg zu Berlin, (Institute for Advanced Study Berlin), Berlin, Germany 5) Department of Psychology, Arizona State University, Tempe, AZ, USA *Corresponding author: Carlo Maley E-mail: carlo.maley@ucsfmedctr.org, cmaley@alum.mit.edu 940 www.bioessays-journal.com Bioessays 36: 940–949,
2014 The Authors. Bioessays published by WILEY Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Review essays