J. Alcock et al Prospects& Overviews■■■■ of their lean twins [77], consistent with the hypothesis that Cravings should be associated with lower lower diversity may affect eating behavior and satiety. parasympathetic (vagal)tone, and blocking the vagus nerve should reduce food cravings Probiotics are associated with weight loss If microbial control is mediated through the vagus nerve, then microbial signals should interfere to some extent with the The addition of probiotics (i.e. purportedly beneficial ingest- physiological regulation coordinated by the vagus nerve. ible microbes)to the diet tends to decrease food intake Vagal tone can be easily measured through respiratory sinus 0> consistent with the hypothesis that greater gut diversity may arrhythmia [87 the extent to which the heart rate changes in limit microbial control over eating behavior. Some Lactoba. response to inspiration and exhalation. We predict that people cillus probiotics have been reported to reduce fat mass and experiencing cravings should have lower vagal tone. Further- improve insulin sensitivity and glucose tolerance, although more, it is possible to block or sever the vagus, which we these effects are not universally reported for all Lactobacillus predict would subdue microbial signaling via the vagus nerve, species [78, 79 a recent study demonstrated that the and thereby alter food preferences. This would be consistent probiotic VSL#3 caused mice to decrease food intake [67]. with studies showing that blocking the vagus nerve can lead Similarly, the probiotic Bifidobacterium breve inhibited weight to weight loss 149, 501 gain in mice given a high fat diet in a dose-dependent manner[80]. Several studies suggest a role for probiotics in weight loss in humans. In one trial, a probiotic yogurt Microbial diversity should affect food choices produced weight loss that was not due to change in energy and satiet intake or exercise [81. Similarly, yogurt was the food most associated with reduced weight gain in a study that monitored Certain features of microbial ecology, such as population size he diet and health of 120, 000 nurses for over 12-20 years [82]. would be expected to influence a microbe s capacity to Further, a randomized, placebo-controlled trial found that manipulate the host. Microbial communities with low alpha probiotic treatment in pregnancy, using L rhamnosus GG and (intrasample) diversity might be more prone to overgrowth by Bifidobacterium lactis along with dietary counseling, reduced one or more species, giving those organisms increased ability abdominal fat at 6 months post-partum [83]. Together these to manufacture behavior-altering neurochemicals and hor results demonstrate that probiotics can lead to weight loss and mones. by comparison, in microbial communities with high regulate energy balance alpha diversity any single microbial species will tend to occur at lower abundance. Highly diverse gut microbiotas tend to be more resistant to invasion by pathogenic species than Predictions and experiments less diverse microbiotas [88]. In addition, a phylogenetically diverse community will likely contain competing groups Changing the microbiota composition will whose influences may counteract each other. Furthermore, change eating behavior in a diverse microbial environment, microbes will likely expend resources on competing and cooperating(e.g. via Prebiotics (i.e. non-digestible compounds that stimulate cross-feeding), rather than on manipulating their host. growth of beneficial microbes), probiotics, antibiotics, fecal Supporting the hypothesis that a more diverse microbiota transplant, and diet changes are potential strategies to alter causes fewer cravings, gastric bypass surgery has a twofold he microbiota. In addition to the proposal that microbiota effect: increasing alpha diversity in the gut microbiota as well transplantation should result in adoptive transfer of food as reducing preference for high fat, high carbohydrate preferences [84], we further predict that inoculation of an foods [89-91]. Food preferences of germfree mice inoculated experimental animal with a microbe that has a specialized with low versus high diversity microbial communities could nutrient requirement, such as seaweed [15, 85, would lead to provide a test of this prediction. Similarly, probiotics that preference for that novel food. increase microbiota diversity in humans are predicted to reduce cravings more than control treatments that do not increase diversity. A consistent diet will select for microbial specialists and lead to preference for those foods Excess energy delivery to the gut may reduce microbial diversity Raising an experimental animal on a simple diet with few types of foods, should select for microbes that specialize on Besides affecting cravings for specific nutrients, conflict those foods. Our hypothesis as to the microbial origin of food between host and microbiota is expected to impact satiety and preferences predicts that these microbes will influence their overall calorie consumption because optimal energy intake is host to choose the foods upon which they specialize. An likely to differ between the host and members of the gut alternative hypothesis, that food cravings result from nutrient microbiota. Excess energy delivered to the gut, beyond what is shortages [86], predicts the opposite: preference for novel optimal for the host, might provide energy substrates fo foods rich in micronutrients that had been lacking in the microbial growth, permitting certain species to bloom previous simple diet. potentially overwhelming inhibition by competitor organisms 944 Bioessays 36: 940-949, C 2014 The Authors Bioessays published by WLEY Perodicals, Inc.of their lean twins [77], consistent with the hypothesis that lower diversity may affect eating behavior and satiety. Probiotics are associated with weight loss The addition of probiotics (i.e. purportedly beneficial ingest￾ible microbes) to the diet tends to decrease food intake, consistent with the hypothesis that greater gut diversity may limit microbial control over eating behavior. Some Lactoba￾cillus probiotics have been reported to reduce fat mass and improve insulin sensitivity and glucose tolerance, although these effects are not universally reported for all Lactobacillus species [78, 79]. A recent study demonstrated that the probiotic VSL#3 caused mice to decrease food intake [67]. Similarly, the probiotic Bifidobacterium breve inhibited weight gain in mice given a high fat diet in a dose-dependent manner [80]. Several studies suggest a role for probiotics in weight loss in humans. In one trial, a probiotic yogurt produced weight loss that was not due to change in energy intake or exercise [81]. Similarly, yogurt was the food most associated with reduced weight gain in a study that monitored the diet and health of 120,000 nurses for over 12–20 years [82]. Further, a randomized, placebo-controlled trial found that probiotic treatment in pregnancy, using L. rhamnosus GG and Bifidobacterium lactis along with dietary counseling, reduced abdominal fat at 6 months post-partum [83]. Together these results demonstrate that probiotics can lead to weight loss and regulate energy balance. Predictions and experiments Changing the microbiota composition will change eating behavior Prebiotics (i.e. non-digestible compounds that stimulate growth of beneficial microbes), probiotics, antibiotics, fecal transplant, and diet changes are potential strategies to alter the microbiota. In addition to the proposal that microbiota transplantation should result in adoptive transfer of food preferences [84], we further predict that inoculation of an experimental animal with a microbe that has a specialized nutrient requirement, such as seaweed [15, 85], would lead to preference for that novel food. A consistent diet will select for microbial specialists and lead to preference for those foods Raising an experimental animal on a simple diet with few types of foods, should select for microbes that specialize on those foods. Our hypothesis as to the microbial origin of food preferences predicts that these microbes will influence their host to choose the foods upon which they specialize. An alternative hypothesis, that food cravings result from nutrient shortages [86], predicts the opposite: preference for novel foods rich in micronutrients that had been lacking in the previous simple diet. Cravings should be associated with lower parasympathetic (vagal) tone, and blocking the vagus nerve should reduce food cravings If microbial control is mediated through the vagus nerve, then microbial signals should interfere to some extent with the physiological regulation coordinated by the vagus nerve. Vagal tone can be easily measured through respiratory sinus arrhythmia [87], the extent to which the heart rate changes in response to inspiration and exhalation. We predict that people experiencing cravings should have lower vagal tone. Further￾more, it is possible to block or sever the vagus, which we predict would subdue microbial signaling via the vagus nerve, and thereby alter food preferences. This would be consistent with studies showing that blocking the vagus nerve can lead to weight loss [49, 50]. Microbial diversity should affect food choices and satiety Certain features of microbial ecology, such as population size, would be expected to influence a microbe’s capacity to manipulate the host. Microbial communities with low alpha (intrasample) diversity might be more prone to overgrowth by one or more species, giving those organisms increased ability to manufacture behavior-altering neurochemicals and hor￾mones. By comparison, in microbial communities with high alpha diversity any single microbial species will tend to occur at lower abundance. Highly diverse gut microbiotas tend to be more resistant to invasion by pathogenic species than less diverse microbiotas [88]. In addition, a phylogenetically diverse community will likely contain competing groups whose influences may counteract each other. Furthermore, in a diverse microbial environment, microbes will likely expend resources on competing and cooperating (e.g. via cross-feeding), rather than on manipulating their host. Supporting the hypothesis that a more diverse microbiota causes fewer cravings, gastric bypass surgery has a twofold effect: increasing alpha diversity in the gut microbiota as well as reducing preference for high fat, high carbohydrate foods [89–91]. Food preferences of germfree mice inoculated with low versus high diversity microbial communities could provide a test of this prediction. Similarly, probiotics that increase microbiota diversity in humans are predicted to reduce cravings more than control treatments that do not increase diversity. Excess energy delivery to the gut may reduce microbial diversity Besides affecting cravings for specific nutrients, conflict between host and microbiota is expected to impact satiety and overall calorie consumption because optimal energy intake is likely to differ between the host and members of the gut microbiota. Excess energy delivered to the gut, beyond what is optimal for the host, might provide energy substrates for microbial growth, permitting certain species to bloom, potentially overwhelming inhibition by competitor organisms J. Alcock et al. Prospects & Overviews .... 944 Bioessays 36: 940–949,
2014 The Authors. Bioessays published by WILEY Periodicals, Inc. Review essays