The Gut–Brain Axis and Its Role in Controlling Eating Behavior in Intestinal Inflammation

Malnutrition represents a major problem in the clinical management of the inflammatory bowel disease (IBD). Presently, our understanding of the cross-link between eating behavior and intestinal inflammation is still in its infancy. Crohn’s disease patients with active disease exhibit strong hedonic desires for food and emotional eating patterns possibly to ameliorate feelings of low mood, anxiety, and depression. Impulsivity traits seen in IBD patients may predispose them to palatable food intake as an immediate reward rather than concerns for future health. The upregulation of enteroendocrine cells (EEC) peptide response to food intake has been described in ileal inflammation, which may lead to alterations in gut–brain signaling with implications for appetite and eating behavior. In summary, a complex interplay of gut peptides, psychological, cognitive factors, disease-related symptoms, and inflammatory burden may ultimately govern eating behavior in intestinal inflammation.     

Microbiota’s Role in Diet-Driven Alterations in Food Intake: Satiety,Energy Balance,and Reward

The gut microbiota plays a key role in modulating host physiology and behavior, particularly feeding behavior and energy homeostasis. There is accumulating evidence demonstrating a role for gut microbiota in the etiology of obesity. In human and rodent studies, obesity and high-energy feeding are most consistently found to be associated with decreased bacterial diversity, changes in main phyla relative abundances and increased presence of pro-inflammatory products. Diet-associated alterations in microbiome composition are linked with weight gain, adiposity, and changes in ingestive behavior. There are multiple pathways through which the microbiome influences food intake. This review discusses these pathways, including peripheral mechanisms such as the regulation of gut satiety peptide release and alterations in leptin and cholecystokinin signaling along the vagus nerve, as well as central mechanisms, such as the modulation of hypothalamic neuroinflammation and alterations in reward signaling. Most research currently focuses on determining the role of the microbiome in the development of obesity and using microbiome manipulation to prevent diet-induced increase in food intake. More studies are necessary to determine whether microbiome manipulation after prolonged energy-dense diet exposure and obesity can reduce intake and promote meaningful weight loss.     

Development of the Hedonic Overeating–Questionnaire (HEDO–Q)

Addictive-like eating is prevalent, but a clear conceptualization and operationalization outside of an addiction framework is lacking. By adopting a biopsychological framework of food reward, this study sought to develop and evaluate a brief self-report questionnaire for the trait assessment of hedonic overeating and dyscontrol. Items in the Hedonic Overeating–Questionnaire (HEDO–Q) were constructed following a rational approach and psychometrically evaluated in a large random sample from the German population (N = 2531). A confirmatory factor analysis supported the unidimensional nature of the six-item HEDO–Q with the three postulated components of wanting, liking, and dyscontrol. Psychometric properties were favorable with good corrected item-total correlations, acceptable item difficulty and homogeneity, and high internal consistency. Population norms were provided. The HEDO–Q revealed strict measurement invariance for sex and partial invariance for age and weight status. Discriminant validity was demonstrated in distinguishing participants with versus without eating disturbances or obesity. Associations with the established measures of eating disorder and general psychopathology supported the convergent and divergent validity of the HEDO–Q. This first evaluation indicates good psychometric properties of the HEDO–Q in the general population. Future validation work is warranted on the HEDO–Q’s stability, sensitivity to change, and predictive and construct validity.     

The Microbiota–Gut–Brain Axis in Depression: The Potential Pathophysiological Mechanisms and Microbiota Combined Antidepression Effect

Depression is a kind of worldwide mental illness with the highest morbidity and disability rate, which is often accompanied by gastrointestinal symptoms. Experiments have demonstrated that the disorder of the intestinal microbial system structure plays a crucial role in depression. The gut–brain axis manifests a potential linkage between the digestion system and the central nervous system (CNS). Nowadays, it has become an emerging trend to treat diseases by targeting intestinal microorganisms (e.g., probiotics) and combining the gut–brain axis mechanism. Combined with the research, we found that the incidence of depression is closely linked to the gut microbiota. Moreover, the transformation of the gut microbiota system structure is considered to have both positive and negative regulatory effects on the development of depression. This article reviewed the mechanism of bidirectional interaction in the gut–brain axis and existing symptom-relieving measures and antidepression treatments related to the gut microbiome.     

The cannabinoid system: a role in both the homeostatic and hedonic control of eating?

Knowledge of the cannabinoid system and its components has expanded greatly over the past decade. There is increasing evidence for its role in the regulation of food intake and appetite. Cannabinoid system activity in the hypothalamus is thought to contribute to the homeostatic regulation of energy balance, under the control of the hormone leptin. A second component of cannabinoid-mediated food intake appears to involve reward pathways and the hedonic aspect of eating. With the cannabinoid system contributing to both regulatory pathways, it presents an attractive therapeutic target for the treatment of both obesity and eating disorders.     

Is sham feeding an animal model of bulimia?

Studies of sham-feeding animals are useful in dissociating the hedonic, orosensory effects of food in the mouth from the satiating and nutritive effects of food in the gut, an operational state highly analogous to binge eating with vomiting. Alteration of hedonic and postingestive responses to food may occur physiologically or may be conditioned; binge-like behavior can result when regulatory processes are sufficiently distorted by biological or environmental changes. An important role for satiety-inducing neuropeptides and central dopamine activity during binging is inferred from the model.     

The Immunopathogenesis of Alzheimer’s Disease Is Related to the Composition of Gut Microbiota

The microbiota–gut–brain axis plays an important role in the development of neurodegenerative diseases. Commensal and pathogenic enteric bacteria can influence brain and immune system function by the production of lipopolysaccharides and amyloid. Dysbiosis of the intestinal microbiome induces local and consecutively systemic immune-mediated inflammation. Proinflammatory cytokines then trigger neuroinflammation and finally neurodegeneration. Immune-mediated oxidative stress can lead to a deficiency of vitamins and essential micronutrients. Furthermore, the wrong composition of gut microbiota might impair the intake and metabolization of nutrients. In patients with Alzheimer’s disease (AD) significant alterations of the gut microbiota have been demonstrated. Standard Western diet, infections, decreased physical activity and chronic stress impact the composition and diversity of gut microbiota. A higher abundancy of “pro-inflammatory” gut microbiota goes along with enhanced systemic inflammation and neuroinflammatory processes. Thus, AD beginning in the gut is closely related to the imbalance of gut microbiota. Modulation of gut microbiota by Mediterranean diet, probiotics and curcumin can slow down cognitive decline and alter the gut microbiome significantly. A multi-domain intervention approach addressing underlying causes of AD (inflammation, infections, metabolic alterations like insulin resistance and nutrient deficiency, stress) appears very promising to reduce or even reverse cognitive decline by exerting positive effects on the gut microbiota.     

Obesity Modulates the Gut Microbiome in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive, molecularly heterogeneous subtype of breast cancer. Obesity is associated with increased incidence and worse prognosis in TNBC through various potential mechanisms. Recent evidence suggests that the gut microbiome plays a central role in the progression of cancer, and that imbalances or dysbiosis in the population of commensal microbiota can lead to inflammation and contribute to tumor progression. Obesity is characterized by low-grade inflammation, and gut dysbiosis is associated with obesity, chronic inflammation, and failure of cancer immunotherapy. However, the debate on what constitutes a “healthy” gut microbiome is ongoing, and the connection among the gut microbiome, obesity, and TNBC has not yet been addressed. This study aims to characterize the role of obesity in modulating the gut microbiome in a syngeneic mouse model of TNBC. 16S rRNA sequencing and metagenomic analyses were performed to analyze and annotate genus and taxonomic profiles. Our results suggest that obesity decreases alpha diversity in the gut microbiome. Metagenomic analysis revealed that obesity was the only significant factor explaining the similarity of the bacterial communities according to their taxonomic profiles. In contrast to the analysis of taxonomic profiles, the analysis of variation of functional profiles suggested that obesity status, tumor presence, and the obesity–tumor interaction were significant in explaining the variation of profiles, with obesity having the strongest correlation. The presence of tumor modified the profiles to a greater extent in obese than in lean animals. Further research is warranted to understand the impact of the gut microbiome on TNBC progression and immunotherapy.     

A Review on the Role of Food-Derived Bioactive Molecules and the Microbiota–Gut–Brain Axis in Satiety Regulation

Obesity is a chronic disease resulting from an imbalance between energy intake and expenditure. The growing relevance of this metabolic disease lies in its association with other comorbidities. Obesity is a multifaceted disease where intestinal hormones such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), produced by enteroendocrine cells (EECs), have a pivotal role as signaling systems. Receptors for these hormones have been identified in the gut and different brain regions, highlighting the interconnection between gut and brain in satiation mechanisms. The intestinal microbiota (IM), directly interacting with EECs, can be modulated by the diet by providing specific nutrients that induce environmental changes in the gut ecosystem. Therefore, macronutrients may trigger the microbiota–gut–brain axis (MGBA) through mechanisms including specific nutrient-sensing receptors in EECs, inducing the secretion of specific hormones that lead to decreased appetite or increased energy expenditure. Designing drugs/functional foods based in bioactive compounds exploiting these nutrient-sensing mechanisms may offer an alternative treatment for obesity and/or associated metabolic diseases. Organ-on-a-chip technology represents a suitable approach to model multi-organ communication that can provide a robust platform for studying the potential of these compounds as modulators of the MGBA.     

The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies

Infectious diseases and infections remain a leading cause of death in low-income countries and a major risk to vulnerable groups, such as infants and the elderly. The immune system plays a crucial role in the susceptibility, persistence, and clearance of these infections. With 70–80% of immune cells being present in the gut, there is an intricate interplay between the intestinal microbiota, the intestinal epithelial layer, and the local mucosal immune system. In addition to the local mucosal immune responses in the gut, it is increasingly recognized that the gut microbiome also affects systemic immunity. Clinicians are more and more using the increased knowledge about these complex interactions between the immune system, the gut microbiome, and human pathogens. The now well-recognized impact of nutrition on the composition of the gut microbiota and the immune system elucidates the role nutrition can play in improving health. This review describes the mechanisms involved in maintaining the intricate balance between the microbiota, gut health, the local immune response, and systemic immunity, linking this to infectious diseases throughout life, and highlights the impact of nutrition in infectious disease prevention and treatment.     

Analysis of the Correlation between Meal Frequency and Obesity among Chinese Adults Aged 18–59 Years in 2015

This study aimed to investigate the relationship between meal frequency and obesity in Chinese adults aged 18 to 59 years. The data came from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance (CACDNS 2015) and provincial dietary environment data from the 2015 National Statistical Yearbook. A total of 34,206 adults aged 18 to 59 who took part in the diet survey were selected as the study participants. A two-level multivariate logistic regression model was used to adjust for the socioeconomic and nutritional status of individuals. For parameter estimation, a numerical integral approach was used to analyze the relationship between meal frequency (including meals at home, the workplace or school dining halls, and eating away from home) and obesity. A two-level “provincial–individual” logistic multivariate regression analysis was performed with obesity as the dependent variable. The two-level multivariate analysis of variance model fitting results showed that after adjusting for the effects of gender, age, occupation, education, marital status, family per capita annual income, provincial gross domestic product (GDP), restaurant industry turnover, consumer price index of EAFH food, and energy intake, the frequency of eating at home was not associated with obesity (all p > 0.05); the frequency of eating at dining halls ≥1 to <2 times per day (OR = 0.784, p = 0.0122) showed a negative association with obesity; the frequency of eating away from home < 1 times per day and ≥1 to <2 times per day were positively correlated with obesity (<1 time per day: OR = 1.123, p = 0.0419; ≥1 to <2 times per day: OR = 1.249, p = 0.0022). The results of the two-level random-intercept logistic multivariate mixed-effects prediction model for obesity in adults aged 18 to 59 years showed that no statistical association was noticed between the frequency of eating at home and obesity in adults aged 18 to 59 years. However, adults who ate out < 1 time and ≥1 to <2 times a day showed higher risks of obesity than those who did not eat out, with OR = 1.131 (95% CI 1.012–1.264) and OR = 1.258 (95% CI 1.099–1.440), while adults who ate at school and workplace dining halls ≥1 to <2 times a day may have a reduced risk of obesity, with OR = 0.790 (95% CI 0.656–0.951). This result could not be found based on the definition of eating out in previous studies. Therefore, it is recommended to exclude nonprofit collective canteens such as school and workplace dining halls from the definition of eating away from home, and to redefine eating out in terms of health effects. At the same time, it is also recommended to strengthen collective nutritional interventions around canteens, improve the nutritious meal system in school and workplace canteens, and create healthy canteens.     

肠道菌群与子宫内膜癌

肠道菌群可完成宿主生理所需的多种功能，如保护宿主免受病原体入侵，调节代谢、发育，维持免疫和神经系统的稳态。尽管肠道菌群受年龄、生活习惯、生理活动、激素水平、抗生素及放射治疗等因素的影响，但其在健康成人体内仍保持稳态。近年来，许多研究报道肠道菌群组成改变与恶性肿瘤和其他疾病的发生发展有关，如炎性肠病、高血压、多囊卵巢综合征（PCOS）、肥胖、糖尿病、结直肠癌、乳腺癌等。有文献报道子宫内膜癌发生与PCOS、肥胖、胰岛素抵抗、高血压、高雌激素水平和年龄等因素有关；肠道菌群稳态的破坏会促进肥胖、高血压、PCOS及高雌激素水平的发生，提示肠道菌群与子宫内膜癌之间可能存在某种关联。本文总结近年来关于肠道菌群与子宫内膜癌风险因素的关联以及可能的肿瘤发生机制的研究进展，为日后继续研究子宫内膜癌的新型诊断、预后和治疗策略提供参考。     

Palatability: response to nutritional need or need-free stimulation of appetite?

The traditional view of palatability was that it reflected some underlying nutritional deficit and was part of a homeostatically driven motivational system. However, this idea does not fit with the common observation that palatability can lead to short-term overconsumption. Here, we attempt to re-evaluate the basis of palatability, first by reviewing the role of salt-need both in the expression of liking for salty tastes, and paradoxically, in dissociating need from palatability, and second by examining the role of palatability in short-term control of appetite. Despite the clarity of this system in animals, however, most salt (NaCl) intake in man occurs in a need-free state. Similar conclusions can be drawn in relation to the palatability of food in general. Importantly, the neural systems underlying the hedonic system relating to palatability and homeostatic controls of eating are separate, involving distinct brain structures and neurochemicals. If palatability was a component of homeostatic control, reducing need-state should reduce palatability. However, this is not so, and if anything palatability exerts a stronger stimulatory effect on eating when sated, and over-consumption induced by palatability may contribute to obesity. Differential responsivity to palatability may be a component of the obese phenotype, perhaps through sensitisation of the neural structures related to hedonic aspects of eating. Together, these disparate data clearly indicate that palatability is not a simple reflection of need state, but acts to promote intake through a distinct hedonic system, which has inputs from a variety of other systems, including those regulating need. This conclusion leads to the possibility of novel therapies for obesity based on modulation of hedonic rather than homeostatic controls. Potential developments are discussed.     

High-Salt Diet Induces Depletion of Lactic Acid-Producing Bacteria in Murine Gut

Dietary habits are amongst the main factors that influence the gut microbiome. Accumulating evidence points to the impact of a high-salt diet (HSD) on the composition and function of the intestinal microbiota, immune system and disease. In the present study, we thus investigated the effects of different NaCl content in the food (0.03%/sodium deficient, 0.5%/control, 4% and 10% NaCl) on the gut microbiome composition in mice. The bacterial composition was profiled using the 16S ribosomal RNA (rRNA) gene amplicon sequencing. Our results revealed that HSD led to distinct gut microbiome compositions compared to sodium-deficient or control diets. We also observed significant reduction in relative abundances of bacteria associated with immuno-competent short-chain fatty acid (SCFA) production (Bifidobacterium, Faecalibaculum, Blautia and Lactobacillus) in HSD-fed mice along with significant enrichment of Clostridia, Alistipes and Akkermansia depending on the sodium content in food. Furthermore, the predictive functional profiling of microbial communities indicated that the gut microbiota found in each category presents differences in metabolic pathways related to carbohydrate, lipid and amino acid metabolism. The presented data show that HSD cause disturbances in the ecological balance of the gastrointestinal microflora primarily through depletion of lactic acid-producing bacteria in a dose-dependent manner. These findings may have important implications for salt-sensitive inflammatory diseases.     

Infants’ First Solid Foods: Impact on Gut Microbiota Development in Two Intercontinental Cohorts

The introduction of solid foods is an important dietary event during infancy that causes profound shifts in the gut microbial composition towards a more adult-like state. Infant gut bacterial dynamics, especially in relation to nutritional intake remain understudied. Over 2 weeks surrounding the time of solid food introduction, the day-to-day dynamics in the gut microbiomes of 24 healthy, full-term infants from the Baby, Food & Mi and LucKi-Gut cohort studies were investigated in relation to their dietary intake. Microbial richness (observed species) and diversity (Shannon index) increased over time and were positively associated with dietary diversity. Microbial community structure (Bray–Curtis dissimilarity) was determined predominantly by individual and age (days). The extent of change in community structure in the introductory period was negatively associated with daily dietary diversity. High daily dietary diversity stabilized the gut microbiome. Bifidobacterial taxa were positively associated, while taxa of the genus Veillonella, that may be the same species, were negatively associated with dietary diversity in both cohorts. This study furthers our understanding of the impact of solid food introduction on gut microbiome development in early life. Dietary diversity seems to have the greatest impact on the gut microbiome as solids are introduced.     

The Role of the Gut Microbiome,Immunity, and Neuroinflammation in the Pathophysiology of Eating Disorders

There is a growing recognition that both the gut microbiome and the immune system are involved in a number of psychiatric illnesses, including eating disorders. This should come as no surprise, given the important roles of diet composition, eating patterns, and daily caloric intake in modulating both biological systems. Here, we review the evidence that alterations in the gut microbiome and immune system may serve not only to maintain and exacerbate dysregulated eating behavior, characterized by caloric restriction in anorexia nervosa and binge eating in bulimia nervosa and binge eating disorder, but may also serve as biomarkers of increased risk for developing an eating disorder. We focus on studies examining gut dysbiosis, peripheral inflammation, and neuroinflammation in each of these eating disorders, and explore the available data from preclinical rodent models of anorexia and binge-like eating that may be useful in providing a better understanding of the biological mechanisms underlying eating disorders. Such knowledge is critical to developing novel, highly effective treatments for these often intractable and unremitting eating disorders.     

Eating motives and the controversy over dieting: eating less than needed versus less than wanted

Anti-dieting sentiment has grown in recent years. Critics of restrained eating suggest that it evokes counter-regulatory responses that render it ineffective or even iatrogenic. However, restrained eaters are not in negative energy balance and overweight individuals show reduced eating problems when losing weight by dieting. A distinction is often drawn between physiological and psychological hunger, and neuroscience research has shown that there is a neurophysiological reality underlying this distinction. The brain has a homeostatic system (activated by energy deficits) and a hedonic system (activated by the presence of palatable food). The omnipresence of highly palatable food in the environment may chronically activate the hedonic appetite system, producing a need to actively restrain eating not just to lose weight but to avoid gaining it. Just as restricting energy intake below homeostatic needs produces physiological deprivation, restricting intake of palatable foods may produce "perceived deprivation" despite a state of energy balance. In summary, the motivation to eat more than one needs appears to be every bit as real, and perhaps every bit as powerful, as the motivation to eat when energy deprived.     

Obesity: Genes,brain, gut,and environment

Obesity, which is assuming alarming proportions, has been attributed to genetic factors, hypothalamic dysfunction, and intestinal gut bacteria and an increase in the consumption of energy-dense food. Obesity predisposes to the development of type 2 diabetes mellitus, hypertension, coronary heart disease, and certain forms of cancer. Recent studies have shown that the intestinal bacteria in obese humans and mice differ from those in lean that could trigger a low-grade systemic inflammation. Consumption of a calorie-dense diet that initiates and perpetuates obesity could be due to failure of homeostatic mechanisms that regulate appetite, food consumption, and energy balance. Hypothalamic factors that regulate energy needs of the body, control appetite and satiety, and gut bacteria that participate in food digestion play a critical role in the onset of obesity. Incretins, cholecystokinin, brain-derived neurotrophic factor, leptin, long-chain fatty acid coenzyme A, endocannabinoids and vagal neurotransmitter acetylcholine play a role in the regulation of energy intake, glucose homeostasis, insulin secretion, and pathobiology of obesity and type 2 diabetes mellitus. Thus, there is a cross-talk among the gut, liver, pancreas, adipose tissue, and hypothalamus. Based on these evidences, it is clear that management of obesity needs a multifactorial approach.     

Full4Health: Understanding food–gut–brain mechanisms across the lifespan in the regulation of hunger and satiety for health

Global levels of overweight and obesity continue to rise and successful interventions to combat this epidemic are limited in number and suitability. When energy intake exceeds that expended, the excess energy accumulates as body fat. Although energy balance is regulated by hypothalamic mechanisms, these can be overridden by the activation of hedonic brain systems. This apparent hierarchy is exacerbated by the widespread availability of inexpensive, palatable and energy‐dense food in the current obesogenic environment, giving rise to energy overconsumption and thereby contributing to the increase in overweight and obesity. The European Commission recognised a need for further research to enhance understanding of the relatively poorly understood mechanisms underpinning hunger and satiety, with a view to providing an evidence base from which novel strategies could be developed to tackle the escalating crisis. Full4Health (Understanding food–gut–brain mechanisms across the lifespan in the regulation of hunger and satiety for health) is a project funded under Framework Programme 7 (FP7), conceived to fulfil this aim. This article describes selected recent research from Full4Health and discusses how new mechanistic findings related to physiological responses to food might be adapted and harnessed to provide alternative ways to address the global problems related to positive energy balance.     

Gut Microbiome Prolongs an Inhibitory Effect of Korean Red Ginseng on High-Fat-Diet-Induced Mouse Obesity

Although the anti-obesity effect of Korean red ginseng (Panax ginseng Meyer) has been revealed, its underlying mechanisms are not clearly understood. Here, we demonstrate an involvement of gut microbiome in the inhibitory effect of Korean red ginseng on high-fat-diet (HFD)-induced mouse obesity, and further provides information on the effects of saponin-containing red ginseng extract (SGE) and saponin-depleted red ginseng extract (GE). Mice were fed with either SGE or GE every third day for one month, and their food intakes, fat weights, plasma glucose, and insulin and leptin levels were measured. Immunofluorescence assays were conducted to measure pancreatic islet size. Stools from the mice were subjected to metagenomic analysis. Both SGE and GE attenuated HFD-induced gain of body weight, reducing HFD-induced increase of food intakes and fat weights. They also reduced HFD-increased plasma glucose, insulin, and leptin levels, decreased both fasting and postprandial glucose concentrations, and improved both insulin resistance and glucose intolerance. Immunofluorescence assays revealed that they blocked HFD-induced increase of pancreatic islet size. Our pyrosequencing of the 16S rRNA gene V3 region from stools revealed that both SGE and GE modulated HFD-altered composition of gut microbiota. Therefore, we conclude that Korean red ginseng inhibits HFD-induced obesity and diabetes by altering gut microbiome.