Transfer with microbiota from lean donors prevents excessive weight gain and restores gut-brain vagal signaling in obese rats maintained on a high fat diet.

Background: The collection of microorganisms, mainly bacteria, which live in the gastrointestinal (GI) tract are collectible known as the gut microbiota. GI bacteria play an active role in regulation of the host's immune system and metabolism, as well as certain pathophysiological processes. Diet is the main factor modulating GI microbiota composition and recent studies have shown that high fat (HF) diets induce detrimental changes, known as dysbiosis, in the GI bacterial makeup. HF diet induced microbiota dysbiosis has been associated with structural and functional changes in gut-brain vagally mediated signaling system, associated with overeating and obesity. Although HF-driven changes in microbiota composition are sufficient to alter vagal signaling, it is unknown if restoring normal microbiota in obesity can improve gut-brain signaling and metabolic outcomes. In this study, we evaluated the effect of lean gut microbiota transfer in obese, vagally compromised, rats on gut-brain communication, food intake, and body weight. Male Sprague-Dawley rats were maintained on regular chow, or 45% HF diet for nine weeks followed by three weeks of microbiota depletion using an antibiotic cocktail. The animals were then divided into four groups (n=10 each): LF - control group on regular chow, LF-LF - chow fed animals that received antibiotics and microbiota from chow fed animals, HF-LF - HF fed animals that received microbiota from chow fed animals, and HF-HF - HF fed animals that received microbiota from HF fed animals. Animals were gavaged with donor microbiota for three consecutive days on week one and once a week thereafter for three more weeks. HF-LF animals received inulin as a prebiotic to aid the establishment of the lean microbiome. Results: We found that transferring a LF microbiota to HF fed animals (HF-LF) reduced caloric intake during the light phase when compared with HF-HF rats and prevented additional excessive weight gain. We did not observe significant changes in the density of vagal afferents terminating in the brainstem among the groups, however, HF-LF animals displayed an increase in postprandial activation of both primary sensory neurons innervating the GI tract and brainstem secondary neurons. Conclusions: We concluded from these data that normalizing microbiota composition in obese rats improves gut-brain communication and restores normal feeding patterns which was associated with a reduction in weight gain.

The gut-brain axis mediates bacterial driven modulation of reward signaling.

OBJECTIVE: Our goal is to investigate if microbiota composition modulates reward signaling and assess the role of the vagus in mediating microbiota to brain communication. METHODS: Male germ-free Fisher rats were colonized with gastrointestinal contents from chow (low fat (LF) ConvLF) or HF (ConvHF) fed rats. RESULTS: Following colonization, ConvHF rats consumed significantly more food than ConvLF animals. ConvHF rats displayed lower feeding-induced extracellular DOPAC levels (a metabolite of dopamine) in the Nucleus Accumbens (NAc) as well as reduced motivation for HF foods compared to ConvLF rats. Dopamine receptor 2 (DDR2) expression levels in the NAc were also significantly lower in ConvHF animals. Similar deficits were observed in conventionally raised HF fed rats, showing that diet-driven alteration in reward can be initiated via microbiota. Selective gut to brain deafferentation restored DOPAC levels, DRD2 expression, and motivational drive in ConvHF rats. CONCLUSIONS: We concluded from these data that a HF-type microbiota is sufficient to alter appetitive feeding behavior and that bacteria to reward communication is mediated by the vagus nerve.

Effect of nutrient composition in a mixed meal on the postprandial glycemic response in healthy people: a preliminary study.

BACKGROUND/OBJECTIVES: The glycemic index (GI) is a measure of the postprandial glucose response (PPGR) to food items, and glycemic load (GL) is a measure of the PPGR to the diet. For those who need to maintain a healthy diet, it is beneficial to regulate appropriate levels of blood glucose. In reality, what influences the meal GI or GL depends on the macronutrient composition and the physical chemistry reactions in vivo. Thus, we investigated whether different macronutrients in a meal significantly affect the PPGR and the validity of calculated GI and GL values for mixed meals. SUBJECTS/METHODS: 12 healthy subjects (6 male, 6 female) were recruited at a campus setting, and subjects consumed a total of 6 test meals one by one, each morning between 8:00 and 8:30 am after 12 h of fasting. PPGR was measured after each consumed meal and serial finger pricks were performed at indicated times. Test meals included 1) 68 g oral glucose, 2) 210 g rice, 3) rice plus 170 g egg white (RE), 4) rice plus 200 g bean sprouts (RS), 5) rice plus 10 g oil (RO), and 6) rice plus, egg white, bean sprouts, and oil (RESO). The incremental area under the curve (iAUC) was calculated to assess the PPGR. Mixed meal GI and GL values were calculated based on the nutrients the subjects consumed in each of the test meals. RESULTS: The iAUC for all meals containing two macronutrients (RS, RO, or RE) were not significantly different from the rice iAUC, whereas, the RESO iAUC (2,237.5 ± 264.9) was significantly lower (P < 0.05). The RESO meal's calculated GI and GL values were different from the actual GI and GL values measured from the study subjects (P < 0.05). CONCLUSIONS: The mixed meal containing three macronutrients (RESO) decreased the PPGR in healthy individuals, leading to significantly lower actual GI and GL values than those derived by nutrient-based calculations. Thus, consuming various macronutrient containing meals is beneficial in regulating PPGR.

Diet, gut microbiota composition and feeding behavior.

Advances in sequencing technologies have allowed for a more complete analysis of the microbiota composition and identification of differences among individuals and/or physiologies. Changes in microbiota composition and associated inflammation have been linked to both metabolic and behavioral disorders, and abnormality in microbiota composition, or dysbiosis, may play a causal role in the etiology and maintenance of these pathologies. There is accumulating evidence showing that the gut microbiota can communicate to the central nervous system to alter host behavior. Supplementation with L. rhamnosus in mice notably causes a decrease in anxiety. Interestingly, these effects are abolished by vagotomy, identifying the vagus nerve as a potential communication route for microbiota-originating signals. Chronic high fat feeding notably leads to remodeling of the vagal afferent pathway and is associated with an increase in energy intake; these effects appear to be mediated by microbiota-induced inflammation. Therefore, preventing bacterial-driven inflammation, via dietary manipulation for example, may have potential therapeutic effects for both metabolic and behavioral disorders.