Glutamine enhances sucrose taste through a gut microbiota-gut-brain axis in Drosophila.

AIMS: Amino acids (AAs) are known to play important roles in various physiological functions. However, their effect on sweet taste perception remains largely unknown. MAIN METHODS: We used Drosophila to evaluate the effect of each AA on sucrose taste perception. Individual AA was supplemented into diets and male flies were fed on these diets for 6 days. The proboscis extension response (PER) assay was applied to assess the sucrose taste sensitivity of treated flies. We further utilized the RNA-seq and germ-free (GF) flies to reveal the underlying mechanisms of sucrose taste sensitization induced by glutamine (Gln). KEY FINDINGS: We found that supplementation of Gln into diets significantly enhances sucrose taste sensitivity. This sucrose taste sensitization is dependent on gut microbiota and requires a specific gut bacterium Acetobacter tropicalis (A. tropicalis). We further found that CNMamide (CNMa) in the gut and CNMa receptor (CNMaR) in dopaminergic neurons are required for increased sucrose taste sensitivity by Gln diet. Finally, we demonstrated that a gut microbiota-gut-brain axis is required for Gln-induced sucrose taste sensitization. SIGNIFICANCE: These findings can advance understanding of the complex interplay between host physiology, dietary factors, and gut microbiota.

Nutritional geometry framework of sucrose taste in Drosophila.

Dietary protein (P) and carbohydrate (C) have a major impact on the sweet taste sensation. However, it remains unclear whether the balance of P and C influences the sweet taste sensitivity. Here, we use the nutritional geometry framework (NGF) to address the interaction of protein and carbohydrates on sweet taste using Drosophila as a model. Our results reveal that high-protein, low-carbohydrate (HPLC) diets sensitize to sweet taste and low-protein, high-carbohydrate (LPHC) diets desensitize sweet taste in both male and female flies. We further investigate the underlying mechanisms of the effects of two diets on sweet taste using RNA sequencing. When compared to the LPHC diet, the mRNA expression of genes involved in the metabolism of glycine, serine, and threonine is significantly upregulated in the HPLC diet group, suggesting these amino acids may mediate sweet taste perception. We further find that sweet sensitization occurs in flies fed with the LPHC diet supplemented with serine and threonine. Our study demonstrates that sucrose taste sensitivity is affected by the balance of dietary protein and carbohydrates possibly through changes in serine and threonine.

Vitamin D and nifedipine in the treatment of Chinese patients with grades I-II essential hypertension: a randomized placebo-controlled trial.

OBJECTIVES: Low vitamin D status has been shown to be associated with hypertension. We planned to research the effect of vitamin D and nifedipine in the treatment of patients with essential hypertension. METHODS: Patients with grades I-II essential hypertension were enrolled in this single-center, double-blind, placebo-controlled trial in Beijing. All patients received a conventional antihypertensive drug (nifedipine, 30 mg/d). One hundred and twenty-six patients were randomly assigned to receive vitamin D (n=63, 2000 IU/d) or a placebo (n=63) as an add-on to nifedipine, by the method of permutated block randomization. Ambulatory blood pressure monitoring was performed at baseline (month 0), at month 3 and at month 6. RESULTS: In vitamin D supplementation group, there was a significant increase in mean 25-hydroxyvitamin D levels from baseline (19.4 ± 11.6 ng/ml) to 6 months (34.1 ± 12.2 ng/ml; p<0.001). At 6 months, the primary end points, a difference in the fall of 24-h mean blood pressure, between the groups was -6.2 mmHg (95% CI -11.2; -1.1) for systolic blood pressure (p<0.001) and -4.2 mmHg (95% CI -8.8; -0.3) for diastolic blood pressure (p<0.001) under intention to treat analysis. In patients with vitamin D <30 ng/ml at baseline (n=113), 24-h mean blood pressure decreased by 7.1/5.7 mmHg (p<0.001). Safety and tolerability were similar among the two groups. CONCLUSIONS: Vitamin D supplementation can reduce blood pressure in patients with hypertension, it can be an adjuvant therapy for patients with grades I-II essential hypertension. CLINICAL TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry, it is available in Website: http://www.chictr.org/cn/; REGISTRATION NUMBER: ChiCTR-ONC-13003840.

[Effects of traditional Chinese medicine on CD4 + T cell counts and HIV viral loads during structured treatment interruption in highly active antiretroviral therapy].

OBJECTIVE: To explore the impacts of traditional Chinese medicine (TCM) on CD4 + T cell counts and human immunodeficiency virus (HIV) viral loads during the course of structured treatment interruption (STI) in highly active antiretroviral therapy (HAART). METHODS: Nineteen HIV/ADIS patients were treated for 14 months as follows: initiated with zidovudine/lamivudine + efavirdine for 6 months, then discontinued the therapy and treated with TCM instead for 2 months. HAART was then reinitiated for another 3 months, and then discontinued and replaced with TCM for another 3 months. The changes of CD4 + T cell counts and HIV viral loads were measured. RESULTS: During the first STI of HAART, 43.8% of patients had no viral rebounds one month later, and 62.6% had stable or increased immune functions; 18.8% had no viral rebounds two months later, and 43.8% had stable or increased immune functions. Changes of viral loads were not significantly different between these two months (P = 0.097), while CD4 + T cell counts significantly decreased two months later compared with one month later (P = 0.043). During the second STI of HAART, 33.3% of patients had no viral rebounds one month later, and 64.3% had stable or increased immune functions; 13.3% had no viral rebounds 3 months later and 46.6% had stable or increased immune functions. Changes of viral loads had significant difference (P = 0. 017), while CD4 + T cell counts at month 12 elevated significantly compared with the baseline (P = 0.014). CONCLUSIONS: TCM can suppress the viral rebounds during STI-HAART, maintain immune functions. However, this effect may decrease along with the prolongation of STI-HAART.