■■■口 Prospects& Overviews J. Alcock et al and the immune system Energy excess is predicted to reduce any specialist gut microbes adapted to that diet would then diversity as a result, leading to a vicious cycle of reduced tend to flourish in the other household members. Even worse diversity, increased manipulation and chronic energy excess. the obesity epidemic could be contagious as a result of Such a positive feedback mechanism could drive long-term obesity-causing microbes transmitted from person to person changes in satiety harming the host by causing obesity a social network study of 12, 067 people found that a person's D Experimental increases in gut microbiota diversity are chance of becoming obese increased by 57% if a friend had expected to change the satiety setpoint, favoring decreased become obese [99 This raises up the possibility that cravings food intake by the host 92 ind associated obesity might not be socially contagious (e. g network study microbial manitu may inhibit density-dependent cold i75). This proposition could be tested by experimentally preference in animals, as above. As others have proposed One explanation for the health benefits of intestinal diversity if food preferences are contagious, then co-housing those is the inhibition of quorum sensing microbes from achieving a manipulated animals with germ-free animals should lead to quorum. Quorum sensing is a cell-cell communication system transmission of food preference [7, 100 used by many gut bacteria to regulate density-dependent conditional strategies, including virulence factor expression and changes in growth. For instance, the common human commensal and pathogen S ases the accessory gene Alternative hypotheses for unhealthy regulator system(AGR)of quorum sensing to regulate toxin eating and obesity and other virulence genes. When S. aureus reaches high density, aGR switches from expression of genes involved in There are a number of existing hypotheses for the prevalence colonization and attachment to those involved in tissue of obesity and our cravings for unhealthy foods, including invasion [93]. Quorum sensing may be one route that microbes addiction/lack of willpower, environmental mismatch, and can use to coordinate behavior in order to manipulate host nutrient shortages. A microbial cause is not mutually eating behavior and enhance resource delivery. It is in the exclusive of other alternatives such as nutrient deprivation host's interest to prevent bacteria from reaching the threshold In this section, we review each of these alternative hypothe- density for expression of virulence toxins and proteases From ses. We find that none of these hypotheses is completely translational perspective, treatments that increase microbial consistent with the data on cravings, food preferences, and diversity might prevent some microbe populations from obesity reaching the density required for a quorum, thus limiting their capacity to manipulate host behavior. Lack of willpower is not sufficient to explain unhealthy eating Interrogation of host and microbiota genomes should reveal a signaling arms race Conventional wisdom often blames unhealthy eating on a lack of willpower. However, binge eating is not just a matter of There has been little work to study the co-evolution of the mental control [101; food cravings are unlike other cravings microbiome and their host genomes [11, 94], and what there is Many other addictions, such as drugs and alcohol, require has tended to focus on mutualism rather than evolutionary ever-increasing doses to maintain the same mood-altering onflict between microbes and their hosts. We hypothesize that effect. This habituation does not happen with food. For some there has been a genomic arms race in which microbes have individuals, the more they indulge their food cravings, the evolved genes to manipulate their hosts(particularly analogs of more enjoyment they get from them [102]. These results, and human signaling molecules such as neuropeptides and recent work showing distinct mechanisms of food-reward and hormones)and corresponding host genes have evolved to morphine sensitization in mice suggest that overeating has a prevent that manipulation where it conflicts with the host's different underlying mechanism from drug abuse, and is not fitness interests. Comparative genomic analyses may reveal consistent with an addiction [103] such co-evolutionary patterns, and they have already identified adaptations specific to obligate commensal microbes [ 95, 96 Mismatch with scarce resources in our ancestral environment is not sufficient to explain unhealthy Food preferences may be contagious eating One intriguing implication of microbially induced cravings Food preferences are thought to arise from a complex is that preferences for certain foods may be contagious [97 interaction between genes, environment, and culture. The Both the fecal and oral microbiota are more similar among modern food environment is vastly different from that of our cohabiting family members compared to non-cohabiting evolutionary ancestors: the human ancestral diet is thought individuals [98]. If the food preferences of one person in a to contain foods far lower in salt, simple carbohydrates, household influence the food consumption of the household, and saturated fat than the typical Western diet [104]. This Bioessays 36: 940-949, 2014 The Authors Bioessays published by WILEY Periodicals, Inc. 945and the immune system. Energy excess is predicted to reduce diversity as a result, leading to a vicious cycle of reduced diversity, increased manipulation and chronic energy excess. Such a positive feedback mechanism could drive long-term changes in satiety, harming the host by causing obesity. Experimental increases in gut microbiota diversity are expected to change the satiety setpoint, favoring decreased food intake by the host [92]. High gut diversity may inhibit density-dependent microbial manipulation One explanation for the health benefits of intestinal diversity is the inhibition of quorum sensing microbes from achieving a quorum. Quorum sensing is a cell–cell communication system used by many gut bacteria to regulate density-dependent conditional strategies, including virulence factor expression and changes in growth. For instance, the common human commensal and pathogen S. aureus uses the accessory gene regulator system (AGR) of quorum sensing to regulate toxin and other virulence genes. When S. aureus reaches high density, AGR switches from expression of genes involved in colonization and attachment to those involved in tissue invasion [93]. Quorum sensing may be one route that microbes can use to coordinate behavior in order to manipulate host eating behavior and enhance resource delivery. It is in the host’s interest to prevent bacteria from reaching the threshold density for expression of virulence toxins and proteases. From a translational perspective, treatments that increase microbial diversity might prevent some microbe populations from reaching the density required for a quorum, thus limiting their capacity to manipulate host behavior. Interrogation of host and microbiota genomes should reveal a signaling arms race There has been little work to study the co-evolution of the microbiome and their host genomes [11, 94], and what there is has tended to focus on mutualism rather than evolutionary conflict between microbes and their hosts. We hypothesize that there has been a genomic arms race in which microbes have evolved genes to manipulate their hosts (particularly analogs of human signaling molecules such as neuropeptides and hormones) and corresponding host genes have evolved to prevent that manipulation where it conflicts with the host’s fitness interests. Comparative genomic analyses may reveal such co-evolutionary patterns, and they have already identified adaptations specific to obligate commensal microbes [95, 96]. Food preferences may be contagious One intriguing implication of microbially induced cravings is that preferences for certain foods may be contagious [97]. Both the fecal and oral microbiota are more similar among cohabiting family members compared to non-cohabiting individuals [98]. If the food preferences of one person in a household influence the food consumption of the household, any specialist gut microbes adapted to that diet would then tend to flourish in the other household members. Even worse, the obesity epidemic could be contagious as a result of obesity-causing microbes transmitted from person to person. A social network study of 12,067 people found that a person’s chance of becoming obese increased by 57% if a friend had become obese [99]. This raises up the possibility that cravings and associated obesity might not be socially contagious (e.g. through changes in norms) as the authors of the social network study suggest [99], but rather truly infectious, like a cold [75]. This proposition could be tested by experimentally selecting for a microbiome that generates a particular food preference in animals, as above. As others have proposed, if food preferences are contagious, then co-housing those manipulated animals with germ-free animals should lead to transmission of food preference [7, 100]. Alternative hypotheses for unhealthy eating and obesity There are a number of existing hypotheses for the prevalence of obesity and our cravings for unhealthy foods, including addiction/lack of willpower, environmental mismatch, and nutrient shortages. A microbial cause is not mutually exclusive of other alternatives such as nutrient deprivation. In this section, we review each of these alternative hypothe￾ses. We find that none of these hypotheses is completely consistent with the data on cravings, food preferences, and obesity. Lack of willpower is not sufficient to explain unhealthy eating Conventional wisdom often blames unhealthy eating on a lack of willpower. However, binge eating is not just a matter of mental control [101]; food cravings are unlike other cravings. Many other addictions, such as drugs and alcohol, require ever-increasing doses to maintain the same mood-altering effect. This habituation does not happen with food. For some individuals, the more they indulge their food cravings, the more enjoyment they get from them [102]. These results, and recent work showing distinct mechanisms of food-reward and morphine sensitization in mice suggest that overeating has a different underlying mechanism from drug abuse, and is not consistent with an addiction [103]. Mismatch with scarce resources in our ancestral environment is not sufficient to explain unhealthy eating Food preferences are thought to arise from a complex interaction between genes, environment, and culture. The modern food environment is vastly different from that of our evolutionary ancestors: the human ancestral diet is thought to contain foods far lower in salt, simple carbohydrates, and saturated fat than the typical Western diet [104]. This ....Prospects & Overviews J. Alcock et al. Bioessays 36: 940–949,
2014 The Authors. Bioessays published by WILEY Periodicals, Inc. 945 Review essays