Could Hop-derived Bitter Compounds Improve Glucose Homeostasis by Stimulating the Secretion of GLP-1?

Hops (Humulus lupulus L.) is by far the greatest contributors to the bitter property of beer. Over the past years, a large body of evidence demonstrated the presence of taste receptors in different locations of the oral cavity. In addition to the taste buds of the tongue, cells expressing these receptors have been identified in olfactory bulbs, respiratory and gastrointestinal tract. In the gut, the attention was mainly directed to sweet Taste Receptor (T1R) and bitter Taste Receptor (T2R) receptors. In particular, T2R has shown to modulate secretion of different gut hormones, mainly Glucagon-like Peptide 1 (GLP-1), which are involved in the regulation of glucose homeostasis and the control of gut motility, thereby increasing the sense of satiety. Scientific interest in the activity of bitter taste receptors emerges because of their wide distribution in the human species and the large range of natural substances that interact with them. Beer, whose alcohol content is lower than in other common alcoholic beverages, contains a considerable amount of bitter compounds and current scientific evidence shows a direct effect of beer compounds on glucose homeostasis. The purpose of this paper is to review the available literature data in order to substantiate the novel hypothesis of a possible direct effect of hop-derived bitter compounds on secretion of GLP-1, through the activation of T2R, with consequent improvement of glucose homeostasis

Nutrition, inflammation and liver-spleen axis

Chronic low-grade systemic inflammation represents a mechanism common to many diseases linked to atherosclerosis-related pathways. There is a growing body of evidence indicating that the combination of food quantity and quality along with genetic susceptibility are able to induce the aberrant activation of innate immune signalling, which initially contributes to chronic low-grade inflammation. Liver represents the central player to inflammatory response. Dietary/metabolic factors contribute to the pathogenesis of Non-alcoholic Fatty Liver Disease (NAFLD), the main causes of liver disease in the Western world. Enlargement of the spleen, central organ in regulating the inflammation-related immune response, is commonly seen in patients with of NAFLD, depicting the so called "liver-spleen axis." The aim of this review was to provide an at-a-glance overview of the possible bi-directional mechanisms linking nutrition and inflammation, particularly pinpointing the inflammatory effects stemmed by nutrition on "liver-spleen axis." In particular, the role of unhealthy diet, healthy dietary patterns, such as the Mediterranean diet style, dietary vitamins and micronutrients, such as vitamin D or Magnesium, and Glucagon-Like Peptide-1, a well-known incretin released in response to meal intake, will be discussed. The highly variability of the inflammatory response highlights the role of expert nutritionists in refining methodologies apt to assess nutritional epidemiology and to apply appropriate dietary intervention to counteract diet-induced inflammation mechanisms

Association of Trimethylamine N-Oxide (TMAO) with the Clinical Severity of Hidradenitis Suppurativa (Acne Inversa)

: In this case-control, cross-sectional, observational study, we evaluated circulating trimethylamine n-oxide (TMAO) levels, a gut-derived metabolite associated with inflammation and cardiometabolic risk, in patients with hidradenitis suppurativa (HS), a highly disabling inflammatory skin disease associated with an elevated prevalence of comorbidities, especially cardiovascular and metabolic diseases. In this study, we enrolled 35 naive-treatment patients with HS and 35 controls, matched for sex, age, and body mass index (BMI). HS Sartorius score was 49.0 (33.0-75.0), while according to the Harley system 12 and 23 patients presented grade 1 and grade 2 severity, respectively. HS patients had a lower adherence to the Mediterranean diet (MD) (p = 0.002), lower phase angle (PhA) (p < 0.001), and higher circulating TMAO levels (p < 0.001) than the control group. HS patients with grade 2 rather than grade 1 of Harley grade severity showed a higher BMI (p = 0.007), waist circumference (p = 0.016), total energy intake (p = 0.005), and lower PhA (p < 0.001) and adherence to the MD (p = 0.003). Of interest, patients with Hurley grade 2 of severity exhibited higher circulating TMAO levels (p < 0.001) compared to grade 1. Circulating TMAO levels showed a positive correlation with HS Sartorius score even after adjustment for confounding covariates, including BMI, waist circumference, adherence to the MD, total energy intake, and PhA (r = 0.570, p = 0.001). Using a linear regression model, circulating TMAO levels and PhA were the main predictors of the clinical severity of HS

Trimethylamine-N-oxide (TMAO) as novel potential biomarker of early predictors of metabolic syndrome

There is a mechanistic link between the gut-derived metabolite trimethylamine-N-oxide (TMAO) and obesity-related diseases, suggesting that the TMAO pathway may also be linked to the pathogenesis of obesity. The Visceral Adiposity Index (VAI), a gender-specific indicator of adipose dysfunction, and the Fatty Liver Index (FLI), a predictor of non-alcoholic fatty liver disease (NAFLD), are early predictors of metabolic syndrome (MetS). In this cross-sectional observational study, we investigated TMAO levels in adults stratified according to Body Mass Index (BMI) and the association of TMAO with VAI and FLI. One hundred and thirty-seven adult subjects (59 males; 21⁻56 years) were enrolled. TMAO levels were detected using HPLC/MS analysis. Homeostatic Model Assessment of Insulin Resistance (HoMA-IR), VAI and FLI were included as cardio-metabolic indices. TMAO levels increased along with BMI and were positively associated with VAI and FLI, independently, on common potential covariates. The most sensitive and specific cut-offs for circulating levels of TMAO to predict the presence of NAFLD-FLI and MetS were ≥8.02 µM and ≥8.74 µM, respectively. These findings allow us to hypothesize a role of TMAO as an early biomarker of adipose dysfunction and NAFLD-FLI in all borderline conditions in which overt MetS is not present, and suggest that a specific cut-off of TMAO might help in identifying subjects at high risk of NAFLD

A New Light on Vitamin D in Obesity: A Novel Association with Trimethylamine-N-Oxide (TMAO)

Vitamin D deficiency and obesity are two public health problems extensively exacerbated over the last years. Among the several mechanisms proposed to account for the complex interplay between vitamin D and obesity, one that has gained particular attention is related to the emerging role of obesity-related changes in gut microbiota and gut-derived metabolites, such as Trimethylamine-N-oxide (TMAO). Vitamin D deficiency and high circulating TMAO levels are associated with body weight and the severity of non-alcoholic fatty liver disease (NAFLD). Considering the link of obesity with vitamin D on the one hand and obesity with TMAO on the other hand, and the central role of the liver in both the vitamin D and TMAO metabolism, the aim of this cross-sectional observational study was first, to confirm the possible inverse association between vitamin D and TMAO across different body mass index (BMI) classes and second, to investigate if this association could be influenced by the presence of NAFLD. One hundred and four adult subjects (50 males and 54 females; 35.38 &plusmn; 7.49 years) were enrolled. The fatty liver index (FLI) was used as a proxy for the diagnosis of NAFLD. Vitamin D deficiency was found in 65 participants (62.5%), while 33 subjects (31.7%) had insufficient levels, and the remaining subjects had sufficient levels of vitamin D. Subjects with both vitamin D deficiency and FLI-NAFLD had the highest TMAO levels (p &lt; 0.001). By stratifying the sample population according to the BMI classes, vitamin D levels decreased significantly along with the increase of plasma TMAO concentrations, with the lowest vitamin D levels and highest TMAO, respectively, in class III obesity. Vitamin D levels showed significant opposite associations with circulating levels of TMAO (r = &minus;0.588, p &lt; 0.001), but this association was no longer significant after the adjustment for FLI values. The highest values of TMAO were significantly associated with the severity of obesity (OR 7.92; p &lt; 0.001), deficiency of vitamin D (OR 1.62; p &lt; 0.001), and FLI-NAFLD (OR 3.79; p &lt; 0.001). The most sensitive and specific cut-off for vitamin D to predict the circulating levels of TMAO was &le;19.83 ng/mL (p &lt; 0.001). In conclusion, our study suggests that high TMAO levels are associated with vitamin D deficiency and NAFLD. Further studies are required to investigate if there is a causality link or whether all of them are simply the consequence of obesity

Very low-calorie ketogenic diet (VLCKD) in the management of hidradenitis suppurativa (Acne Inversa): an effective and safe tool for improvement of the clinical severity of disease. Results of a pilot study

Abstract Background Hidradenitis suppurativa (HS), an inflammatory-based dermatological condition often associated with obesity, poses significant challenges in management. The very low-calorie ketogenic diet (VLCKD) has shown efficacy in addressing obesity, related metabolic disorders, and reducing chronic inflammation. However, its effects on HS remain underexplored. In this prospective pilot study, we aimed to investigate the impact of a 28-day active phase of VLCKD on HS in a sample of treatment-naive women with HS and excess weight. Methods Twelve women with HS and overweight or obesity (BMI 27.03 to 50.14 kg/m2), aged 21 to 54 years, meeting inclusion/exclusion criteria and agreeing to adhere to VLCKD, were included. Baseline lifestyle habits were assessed. The Sartorius score was used to evaluate the clinical severity of HS. Anthropometric parameters (waist circumference, weight, height, and body mass index), body composition via bioelectrical impedance analysis, levels of trimethylamine N-oxide (TMAO), oxidized low-density lipoprotein (oxLDL), and derivatives of reactive oxygen metabolites (dROMs) were assessed at baseline and after 28 days of the active phase of VLCKD. Results VLCKD led to general improvements in anthropometric parameters and body composition. Notably, a significant reduction in the Sartorius score was observed after the intervention (Δ%: − 24.37 ± 16.64, p < 0.001). This reduction coincided with significant decreases in TMAO (p < 0.001), dROMs (p = 0.001), and oxLDL (p < 0.001) levels. Changes in the Sartorius score exhibited positive correlations with changes in TMAO (p < 0.001), dROMs (p < 0.001), and oxLDL (p = 0.002). Conclusion The 28-day active phase of VLCKD demonstrated notable improvements in HS severity and associated metabolic markers, highlighting the potential utility of VLCKD in managing HS and its association with metabolic derangements in women with overweight or obesity

Depletion of circulating IgM memory B cells predicts unfavourable outcome in COVID-19

Impaired immune responses have been hypothesised to be a possible trigger of unfavourable outcomes in coronavirus disease 2019 (COVID-19). We aimed to characterise IgM memory B cells in patients with COVID-19 admitted to an internal medicine ward in Northern Italy. Overall, 66 COVID-19 patients (mean age 74 ± 16.6 years; 29 females) were enrolled. Three patients (4.5%; 1 female) had been splenectomised and were excluded from further analyses. Fifty-five patients (87.3%) had IgM memory B cell depletion, and 18 (28.6%) died during hospitalisation (cumulative incidence rate 9.26/100 person-week; 5.8–14.7 95% CI). All patients who died had IgM memory B cell depletion. A superimposed infection was found in 6 patients (9.5%), all of them having IgM memory B cell depletion (cumulative incidence rate 3.08/100 person-week; 1.3–6.8 95% CI). At bivariable analyses, older age, sex, number of comorbidities, and peripheral blood lymphocyte count &lt; 1500/µl were not correlated with IgM memory B cell depletion. A discrete-to-marked reduction of the B-cell compartment was also noticed in autoptic spleen specimens of two COVID-19 patients. We conclude that IgM memory B cells are commonly depleted in COVID-19 patients and this correlates with increased mortality and superimposed infections