J. Alcock et al Prospects& Overviews■■■■ Figure 1. Like microscopic puppetmasters RECEPTOR ALTERATION REWARD nisms including microbial manipulation of eward pathways, production of toxins alter mood(shown in pink, diffusing from a microbe), changes to receptors including VAGAL taste receptors, and hijacking of neL otrans mission via the vagus nerve(gray), which is CONTROL the main neural axis between the gut and the brain Negative mood n gut[43] Enteric receptors respond to specific bacteria [48] intestinal epithelium when certain nutrients are absent, increased intestinal expression of cannabinoid and opioid raising the possibility that microbes manipulate behaviors receptors in mouse and rat intestines, and had similar through pain signaling. In accord with this hypothesis, effects in human epithelial cell culture [43. These results bacterial virulence proteins have been shown to activate pain suggest that microbes could influence food preferences by receptors [38]. Moreover, pain perception (nociception) altering receptor expression or transduction. Changes in requires the presence of an intestinal microbiota in mice [39 taste receptor expression and activity have been reported and fasting has been shown to increase nociception in rodents after gastric bypass surgery, a procedure that also changes by a vagal nerve mechanism [40] gut microbiota and alters satiety and food preferences (reviewed in [44D Microbes modulate host receptor expression Microbes can influence hosts through neural One route to manipulation of host eating behavior is to alter mechanisms the preferences of hosts through changing receptor expres- sion. One study found that germ-free mice had altered taste Gut microbes may manipulate eating behavior by hijacking eceptors for fat on their tongues and in their intestines their host's nervous system. Evidence shows that microbes compared to mice with a normal microbiome [41]. In another can have dramatic effects on behavior through the micro- experiment, germ free mice preferred more sweets and biome-gut-brain axis [6, 45, 46]. The vagus nerve is a central had greater numbers of sweet taste receptors in the gastro- actor in this communication axis, connecting the 100 million intestinal tract compared to normal mice [42. In addition, neurons of the enteric nervous system in the gut [47] to the L. acidophilus NCFM, administered orally as a probiotic, base of the brain at the medulla. Enteric nerves have receptors 942 Bioessays 36: 940-949, C 2014 The Authors Bioessays published by WLEY Perodicals, Inc.intestinal epithelium when certain nutrients are absent, raising the possibility that microbes manipulate behaviors through pain signaling. In accord with this hypothesis, bacterial virulence proteins have been shown to activate pain receptors [38]. Moreover, pain perception (nociception) requires the presence of an intestinal microbiota in mice [39] and fasting has been shown to increase nociception in rodents by a vagal nerve mechanism [40]. Microbes modulate host receptor expression One route to manipulation of host eating behavior is to alter the preferences of hosts through changing receptor expres￾sion. One study found that germ-free mice had altered taste receptors for fat on their tongues and in their intestines compared to mice with a normal microbiome [41]. In another experiment, germ free mice preferred more sweets and had greater numbers of sweet taste receptors in the gastro￾intestinal tract compared to normal mice [42]. In addition, L. acidophilus NCFM, administered orally as a probiotic, increased intestinal expression of cannabinoid and opioid receptors in mouse and rat intestines, and had similar effects in human epithelial cell culture [43]. These results suggest that microbes could influence food preferences by altering receptor expression or transduction. Changes in taste receptor expression and activity have been reported after gastric bypass surgery, a procedure that also changes gut microbiota and alters satiety and food preferences (reviewed in [44]). Microbes can influence hosts through neural mechanisms Gut microbes may manipulate eating behavior by hijacking their host’s nervous system. Evidence shows that microbes can have dramatic effects on behavior through the micro￾biome-gut-brain axis [6, 45, 46]. The vagus nerve is a central actor in this communication axis, connecting the 100 million neurons of the enteric nervous system in the gut [47] to the base of the brain at the medulla. Enteric nerves have receptors TOXINS REWARD VAGAL CONTROL RECEPTOR ALTERATION Negative mood induced by toxins [38,39] may increase eating [109] Microbes release toxins in absence of nutrients [33-37] Taste receptors altered by microbes, affect eating behavior [41-44] Microbes alter cannabinoid and opioid receptors in gut [43] Vagus nerve interruption leads to weight loss [49,50] Enteric receptors respond to specific bacteria [48] High levels of dopamine and serotonin in gut [58,59] Microbes have genes for human neurotransmitters [8,55-57,60] Figure 1. Like microscopic puppetmasters, microbes may control the eating behavior of hosts through a number of potential mecha￾nisms including microbial manipulation of reward pathways, production of toxins that alter mood (shown in pink, diffusing from a microbe), changes to receptors including taste receptors, and hijacking of neurotrans￾mission via the vagus nerve (gray), which is the main neural axis between the gut and the brain. J. Alcock et al. Prospects & Overviews .... 942 Bioessays 36: 940–949,
2014 The Authors. Bioessays published by WILEY Periodicals, Inc. Review essays