Improvement of Lipoprotein Profile and Metabolic Endotoxemia by a Lifestyle Intervention That Modifies the Gut Microbiota in Subjects With Metabolic Syndrome

Abstract

BackgroundMetabolic syndrome (MetS) is a serious health problem over the world; thus, the aim of the present work was to develop a lifestyle intervention to decrease the dysbiosis of gut microbiota and reduce the biochemical abnormalities of MetS.Methods and ResultsThe prevalence of MetS was evaluated in 1065 subjects of Mexico City, Mexico, and the gut microbiota in a subsample. Subjects with MetS were selected for a pragmatic study based on a lifestyle intervention with a low‐saturated‐fat diet, reduced‐energy intake, with functional foods and physical activity, and a second group was selected for a randomized control‐placebo study to assess the gut microbiota after the dietary intervention. Prevalence of MetS was 53%, and the higher the body mass index, the higher the gut microbiota dysbiosis. The higher the Homeostatic Model Assessment for Insulin Resistance, the lower the high‐density lipoprotein cholesterol concentration. The pragmatic study revealed that after 15 days on a low‐saturated‐fat diet, there was a 24% reduction in serum triglycerides; and after a 75‐day lifestyle intervention, MetS was reduced by 44.8%, with a reduction in low‐density lipoprotein cholesterol, small low‐density lipoprotein particles, glucose intolerance, lipopolysaccharide, and branched‐chain amino acid. The randomized control‐placebo study showed that after the lifestyle intervention, there was a decrease in the dysbiosis of the gut microbiota associated with a reduction in the Prevotella/ Bacteroides ratio and an increase in the abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii.ConclusionsA lifestyle intervention significantly decreased MetS components, small low‐density lipoprotein particle concentration, gut microbiota dysbiosis, and metabolic endotoxemia, reducing the risk of atherosclerosis.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT03611140.

The Role of the Gut Microbiota in Lipid and Lipoprotein Metabolism

“…Recently, a lifestyle intervention study was performed with a low-saturated-fat and reduced-energy intake diet in 1065 metabolic syndrome patients and healthy subjects [46]. The metabolic syndrome patients had at least three of the following factors: central obesity (waist circumference ≥80 cm in women and ≥90 cm in men), fasting blood glucose ≥ 5.50 mmol/L, triglyceride concentration ≥ 1.65 mmol/L, low levels of HDL cholesterol (<1.00 mmol/L in men and <1.25 mmol/L in women), and systolic and/or diastolic blood pressure ≥ 130/85 mm Hg.…”

“…A short period (15 days) of diet intervention decreased the level of serum triglycerides, while the longer-term (75 days) intervention led to a significant reduction in VLDL, CM, LDL, small HDL particle, and improved glucose tolerance in 44.8% of metabolic syndrome patients. Moreover, the lifestyle intervention ameliorated gut dysbiosis, resulting in a reduction in the P/ B ratio and an increase in the abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii [46].…”

Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects

“…This situation has been accompanied by an increase in metabolic abnormalities, mainly insulin resistance and dyslipidemias that have increased the rate of morbimortality worldwide 2. In order to attend to this problem, several clinical and nutritional strategies have been developed to attenuate some of the altered metabolic conditions 3. There is evidence that strategies that increase the capacity to oxidize fatty acids in the body of obese animals can contribute to improve insulin sensitivity and reduce the hyperlipidemia 4…”

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

“…Observational studies comparing fecal microbiota from healthy subjects to patients with different types of metabolic diseases strongly suggest that the gut microbiota plays a significant role in the etiology and development of obesity and diabetes that is accompanied by a low-grade inflammation known as metabolic endotoxemia. 2,3 Currently, the increase in obesity rates worldwide has been associated with an increase in the intake of energy-dense foods that are not only high in fat but also high in sugar. 4 To combat this trend without compromising our preference for sweet foods, noncaloric sweeteners (NCS) have been developed to reduce caloric intake, and consumption of other natural sweeteners such as brown sugar or honey has been promoted.…”

“…Observational studies comparing fecal microbiota from healthy subjects to patients with different types of metabolic diseases strongly suggest that the gut microbiota plays a significant role in the etiology and development of obesity and diabetes that is accompanied by a low-grade inflammation known as metabolic endotoxemia. 2 , 3 …”