The Microbiota and the Gut–Brain Axis in Controlling Food Intake and Energy Homeostasis

Abstract

Obesity currently represents a major societal and health challenge worldwide. Its prevalence has reached epidemic proportions and trends continue to rise, reflecting the need for more effective preventive measures. Hypothalamic circuits that control energy homeostasis in response to food intake are interesting targets for body-weight management, for example, through interventions that reinforce the gut-to-brain nutrient signalling, whose malfunction contributes to obesity. Gut microbiota–diet interactions might interfere in nutrient sensing and signalling from the gut to the brain, where the information is processed to control energy homeostasis. This gut microbiota–brain crosstalk is mediated by metabolites, mainly short chain fatty acids, secondary bile acids or amino acids-derived metabolites and subcellular bacterial components. These activate gut–endocrine and/or neural-mediated pathways or pass to systemic circulation and then reach the brain. Feeding time and dietary composition are the main drivers of the gut microbiota structure and function. Therefore, aberrant feeding patterns or unhealthy diets might alter gut microbiota–diet interactions and modify nutrient availability and/or microbial ligands transmitting information from the gut to the brain in response to food intake, thus impairing energy homeostasis. Herein, we update the scientific evidence supporting that gut microbiota is a source of novel dietary and non-dietary biological products that may beneficially regulate gut-to-brain communication and, thus, improve metabolic health. Additionally, we evaluate how the feeding time and dietary composition modulate the gut microbiota and, thereby, the intraluminal availability of these biological products with potential effects on energy homeostasis. The review also identifies knowledge gaps and the advances required to clinically apply microbiome-based strategies to improve the gut–brain axis function and, thus, combat obesity.

Hypothalamic Regulation of Obesity

“…Hypothalamic circuits controlling energy balance in response to feeding are also mediated by the gut-to-brain nutrient signaling, whose disruption leads to obesity. As extensively reported by Romani-Perez et al [13], aberrant feeding patterns or unhealthy diets might alter gut microbiota-diet interactions and modify nutrient-sensing information from the gut to the hypothalamus, impairing energy homeostasis. They identify microbiomebased strategies to improve the gut-brain axis function and hence combat obesity.…”

“…In this Special Issue, we report on the most recent insights into the hypothalamic circuitries and pathways involving neurons [3][4][5][6][7], astrocytes [8,9], and microglia [10,11] in obesity development and associated complications. The emerging contribution of astrocyte-neuron [9] and microglia-neuron cross-talks [12] in the hypothalamus and the contribution of microbiota and the gut-brain axis controlling food intake and energy homeostasis [13] are also presented in this Special Issue (Figure 1).…”

Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia

“…Obesity is associated with altered gut microbial composition in mice and humans, and the trait is transmissible as colonization of germ-free mice with microbiota from obese mice led to a significant increase in body fat compared to colonization with microbiota from lean mice ( Turnbaugh et al, 2006 ), suggesting that gut microbiome is part of the host metabolic system actively regulating energy balance ( Bäckhed et al, 2004 ). It has also been suggested that microbiome plays a crucial role in the communication between the gut and brain (microbiota-gut-brain axis), which is essential for the regulation of energy homeostasis ( Romaní-Pérez et al, 2021 ; van Son et al, 2021 ) as well as the development and functions of the nervous system ( Chen et al, 2021 ; Gwak and Chang, 2021 ). Consequently, altered gut microbiota (dysbiosis) has been implicated in a number of chronic inflammatory diseases, such as diabetes ( Zawada et al, 2020 ; Rodriguez and Delzenne, 2021 ) and neurodegenerative disorders, including AD ( Jiang et al, 2017 ; Chen et al, 2021 ; Leblhuber et al, 2021 ; Romanenko et al, 2021 ).…”

Stringent Response in Mycobacteria: From Biology to Therapeutic Potential

“…Bacteria encounter constantly changing environments that may threaten their survival and existence; hence, it is particularly important to study their survival strategies in different model systems [1][2][3]. These strategies include several sensory mechanisms and signaling pathways that are required to overcome such threats [4][5][6][7][8][9]. These mechanisms help bacteria to sense the environmental cues and generate an appropriate adaptive response.…”