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The development of metabolic endotoxemia is dependent on the type of sweetener and the presence of saturated fat in the diet.

ABSTRACT: Fat and sweeteners contribute to obesity. However, it is unknown whether specific bacteria are selectively modified by different caloric and noncaloric sweeteners with or without a high-fat diet (HFD). Here, we combined extensive host phenotyping and shotgun metagenomics of the gut microbiota to investigate this question. We found that the type of sweetener and its combination with an HFD selectively modified the gut microbiota. Sucralose and steviol glycosides led to the lowest α-diversity of the gut microbiota. Sucralose increased the abundance of B. fragilis in particular, resulting in a decrease in the abundance of occludin and an increase in proinflammatory cytokines, glucose intolerance, fatty acid oxidation and ketone bodies. Sucrose+HFD showed the highest metabolic endotoxemia, weight gain, body fat, total short chain fatty acids (SCFAs), serum TNFα concentration and glucose intolerance. Consumption of sucralose or sucrose resulted in enrichment of the bacterial genes involved in the synthesis of LPS and SCFAs. Notably, brown sugar and honey were associated with the absence of metabolic endotoxemia, increases in bacterial gene diversity and anti-inflammatory markers such as IL-10 and sIgA, the maintenance of glucose tolerance and energy expenditure, similar to the control group, despite the consumption of an HFD. These findings indicate that the type of sweetener and an HFD selectively modify the gut microbiota, bacterial gene enrichment of metabolic pathways involved in LPS and SCFA synthesis, and metabolic endotoxemia associated with different metabolic profiles.

SUBMITTER: Sanchez-Tapia M

PROVIDER: S-EPMC7524302 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSaturated-fat intake and endotoxemia can impair cognition. However, their acute impact on cognitive performance is unknown.ObjectiveThis study assessed the impact of 2 high-fat meals and endotoxemia on attention.MethodsIn this double-blind, randomized crossover trial, 51 women (n = 32 breast cancer survivors, n = 19 noncancer controls; mean ± SD age: 53 ± 8 y) completed the Continuous Performance Test (CPT) and had their blood drawn to assess endotoxemia markers LPS binding protein (LBP), soluble CD14 (sCD14), and the LBP to sCD14 ratio 1 h prior to eating either a high-saturated-fat meal or a high-oleic-sunflower-oil meal. Women again completed the CPT 5 h postmeal. At 1 to 4 wk later, women completed the same protocol but consumed the other meal.ResultsIn adjusted models, women had more difficulty distinguishing target stimuli from distractors after consuming the high-saturated-fat meal than they did after the oleic-sunflower-oil meal (B = 4.44, SE = 1.88, P = 0.02). Women with higher baseline LBP had less consistent response times (B = 0.002, SE = 0.0008, P = 0.04). Those with higher LBP and LBP:sCD14 were less able to sustain their attention throughout the entire CPT, as reflected by their progressively slower (B = 0.002, SE = 0.0006, P = 0.003; and B = 2.43, SE = 0.090, P = 0.008, respectively) and more erratic (B = 0.003, SE = 0.0008, P < 0.0001; and B = 3.29, SE = 1.17, P = 0.006, respectively) response times. Additionally, women with higher baseline LBP or sCD14 were less able to maintain or increase response speeds at higher interstimulus intervals (B = 0.002, SE = 0.0006, P = 0.02; and B = 0.006, SE = 0.003, P = 0.03, respectively), indicating greater difficulty adapting to changing task demands. Significant meal type by LBP and LBP:sCD14 interactions emerged (P < 0.05), such that high LBP and LBP:sCD14 erased between-meal cognitive differences, uniformly impairing performance.ConclusionsThese results suggest that higher LBP, sCD14, and LBP:sCD14 and saturated-fat intake individually and jointly influence attention. Endotoxemia may override the relative cognitive benefit of healthier oil choices.This trial is registered at clinicaltrials.gov as NCT04247763.

Project description:The gut microbiome is involved in metabolic disorders. Osteopontin (OPN), as a key cytokine, contributes to various inflammation-related diseases. The underlying role of OPN in the microbiome remains poorly understood. Here, we investigated whether OPN could modulate metabolic disorders by affecting gut microbiota. In our present study, we found that the expression of OPN was elevated in individuals with obesity compared to that observed in healthy controls. There was a positive correlation between plasma OPN levels and body mass index (BMI) in humans. Moreover, OPN significantly exacerbated lipid accumulation and metabolic disorders in high-fat diet (HFD)-fed mice. Importantly, OPN significantly aggravated HFD-induced gut dysbiosis with a key signature profile. Fecal microbiota transplantation also supported the role of OPN in HFD-induced metabolic disorders in a microbiota-dependent manner. Moreover, the microbiome shift of OPN-deficient mice would be compensated to resemble those of wild-type mice by feeding with either OPN-containing milk or recombinant OPN protein in vivo. Furthermore, metagenomic analysis showed that OPN induced a higher abundance of Dorea and a lower abundance of Lactobacillus, which were positively and negatively correlated with body weight, respectively. Indeed, the abundance of Dorea was significantly decreased after Lactobacillus administration, suggesting that OPN may regulate the intestinal abundance of Dorea by reducing the colonization of Lactobacillus. We further confirmed that OPN decreased the adhesion of Lactobacillus to intestinal epithelial cells through the Notch signaling pathway. This study suggested that OPN could exacerbate HFD-induced metabolic dysfunctions through the OPN-induced alteration of the gut microbiome. Therefore, OPN could be a potential therapeutic target for metabolic syndrome. IMPORTANCE Gut microbiota are involved in metabolic disorders. However, microbiome-based therapeutic interventions are not always effective, which might be due to interference of the host factors. Here, we identified a strong positive correlation between OPN levels and BMI in humans. Next, we confirmed that OPN could aggravate high-fat diet-induced metabolic disorders in mice. Importantly, we found that fecal microbiota transplantation from OPN-deficient mice significantly alleviated metabolic disorders in WT mice. OPN directly induces the remodeling of the gut microbiota both in vitro and in vivo. These findings indicate that OPN could contribute to metabolic disorders by inducing an alteration of gut microbiota. OPN regulated the relative abundance of Lactobacillus by decreasing the adhesion of Lactobacillus to intestinal epithelial cells through the Notch signaling pathway. These data identify OPN as a potential pharmaceutical target for weight control and for the treatment of metabolic disorders.

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The development of metabolic endotoxemia is dependent on the type of sweetener and the presence of saturated fat in the diet.

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