Gut Microbiota-Mediated Inflammation and Gut Permeability in Patients with Obesity and Colorectal Cancer.

Obesity is considered an important factor that increases the risk of colorectal cancer (CRC). So far, the association of gut microbiota with both obesity and cancer has been described independently. Nevertheless, a specific obesity-related microbial profile linked to CRC development has not been identified. The aim of this study was to determine the gut microbiota composition in fecal samples from CRC patients with (OB-CRC) and without obesity (L-CRC) compared to the microbiota profile present in non-obese healthy controls (L-HC), in order to unravel the possible relationship between gut microbiota and microbial-derived metabolite trimethylamine N-oxide (TMAO), the inflammatory status, and the intestinal permeability in the context of obesity-associated CRC. The presence of obesity does not induce significant changes in the diversity and richness of intestinal bacteria of CRC patients. Nevertheless, OB-CRC patients display a specific gut microbiota profile characterized by a reduction in butyrate-producing bacteria and an overabundance of opportunistic pathogens, which in turn could be responsible, at least in part, for the higher levels of proinflammatory cytokine IL-1ß, the deleterious bacterial metabolite TMAO, and gut permeability found in these patients. These results suggest a possible role of obesity-related gut microbiota in the development of CRC, which could give new clues for the design of new diagnostic tools for CRC prevention.

Influence of the microbiome on radiotherapy-induced oral mucositis and its management: A comprehensive review.

Radiation-induced mucositis is the most common, debilitating and painful acute toxicity associated with active treatment in head and neck cancer area, severely affecting more than 65% of patients. Oral microbiota significantly changes during cancer therapy and appears to be involved on its pathophysiology. This review aims to present a comprehensive update of new etiopathogenic factors and treatments that may decrease the incidence of mucositis, mainly modifications of dietary interventions to modify microbiome. Despite advances in recent years, its management is mainly symptomatic opioid-based with variable results on different substances analyzed for its prevention. Immunonutrition seems to play a significant role, particularly the supplementation of compounds such as fatty acids, polyphenols or selected probiotics have shown to promote commensal bacteria diversity and reduced incidence of ulcerative mucositis. Modification of the microbiome is a promising preventive treatment for mucositis although its evidence is still scarce. Large studies are needed to demonstrate the efficacy of interventions on microbiome and its clinical impact on radiation-induced mucositis.

Relationship of Zonulin with Serum PCSK9 Levels after a High Fat Load in a Population of Obese Subjects.

Despite the fact that circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) remain unchanged after fat load in healthy lean individuals, PCSK9 has been suggested to have a role in postprandial lipemia regulation in obese individuals. On the other hand, intestinal permeability and endotoxemia have been observed to increase more in obese individuals than in non-obese individuals after a lipid load. This study aimed to analyze the relationship between PCSK9, intestinal permeability, and endotoxemia after a high fat load in obese individuals. We included 39 individuals with morbid obesity. Serum PCSK9 levels, intestinal permeability marker (zonulin), endotoxemia markers (LPS and LBP), and lipid parameters were measured before and after 3 h of fat load. A significant rise in triglycerides, apolipoprotein A1, zonulin, LPS, and LBP, and a significant decline in PCSK9, were observed after a lipid load. Linear regression analysis showed that low-density lipoprotein cholesterol (LDL-C) was independently related to PCSK9 at baseline, whereas both zonulin and LDL-C were independently related to PCSK9 levels after fat load. A relationship between zonulin and PCSK9 levels after fat load in individuals with morbid obesity may exist.

Adiposity is Associated with Decreased Serum 17-Hydroxyprogesterone Levels in Non-Diabetic Obese Men Aged 18-49: A Cross-Sectional Study.

Obesity is associated with decreased circulating testosterone levels, the main male sex hormone. However, there are a number of different male sex hormones whose dynamics remain poorly understood regarding this pathology. In this regard, 17 hydroxyprogesterone (17-OH progesterone), as an important precursor of testosterone synthetized in testes and adrenal glands, could play an essential role in testosterone deficiency in male obesity. Moreover, similarly to testosterone, 17-OH progesterone could be closely associated with visceral fat distribution and metabolic dysfunction. Thus, the aim of this study was to assess serum 17-OH progesterone levels in non-diabetic obese young men and to evaluate their relationship with clinical, analytical, and anthropometric parameters. We conducted a cross-sectional study including 266 non-diabetic men with obesity (BMI ≥ 30 kg/m2) aged 18-49 years; 17-OH progesterone and total testosterone (TT) were determined by high-performance liquid chromatography mass spectrometry. 17-OH progesterone levels were significantly lower in tertile 3 of body fat percentage in comparison with tertile 1 (0.74 ng/mL vs. 0.94 ng/mL, p < 0.01; Bonferroni correction) and in comparison with tertile 2 (0.74 ng/mL vs. 0.89 ng/mL, p = 0.02; Bonferroni correction). 17-OH progesterone levels correlated negatively with weight, BMI, waist circumference, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and visceral fat, and positively with TT, free testosterone (FT), luteinizing hormone, and fat-free mass percentage. Multivariate linear-regression analysis showed that body fat percentage and HOMA-IR were inversely associated with 17-OH progesterone levels, while FT and ACTH were positively linked to circulating 17-OH progesterone levels. In conclusion, in a population of non-diabetic obese young men, 17-OH progesterone levels were inversely associated with adiposity. Body fat percentage and insulin resistance were negatively related to 17-OH progesterone levels, whereas FT and ACTH levels were positively associated with 17-OH progesterone levels.