Efeitos da intervenção com uma formulação probiótica de Limosilactobacillus fermentum sobre a microbiota intestinal e parâmetros cardiometabólicos em ratos

• Ano de defesa: 2021
• Autor(a) principal: Ferreira, Georgianna de Araújo Henriques
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal da Paraíba; Brasil; Ciências Fisiológicas; Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas; UFPB
• Palavras-chave em Português: Dislipidemia; Probióticos; Microbiota intestinal; Hiperatividade simpática; Dyslipidemia; Probiotics; Intestinal microbiota; Sympathetic hyperactivity; Arterial hypertension; CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA
• Link de acesso: https://repositorio.ufpb.br/jspui/handle/123456789/29595

Systemic Arterial Hypertension is a chronic, non-communicable disease of multifactorial etiology. The sedentary lifestyle associated with a food context rich in saturated fatty acids (SFA) and sugars culminates in dyslipidemia, which can favor the development of SAH. In turn, SAH developed in a dyslipidemic setting is associated with qualitative and quantitative changes in the intestinal microbiome, characterizing intestinal dysbiosis. Systemic alterations appear together with intestinal dysbiosis, such as increased oxidative stress, inflammation and sympathetic hyperactivity, reflecting higher levels of blood pressure (BP). The intestinal microbiome can be recovered from the inoculation of bacteria with probiotic potential and this intestinal modulation can affect BP control organs, as in previous experimental studies probiotics attenuated the autonomic dysfunction and in clinical studies they reduced risk factors for cardiovascular diseases. Limosiactobacillus fermentum strains showed good probiotic characteristics (aggregation, antagonism, adhesion, among others) and exerted a lipid-lowering role in rats, however, their role in cardiovascular and metabolic disorders has not been studied. Therefore, the present study investigated the effects of administering a probiotic formulation of L. fermentum (strains 139, 263 and 296) on cardiorespiratory and metabolic parameters and changes in the intestinal microbiota of rats at 90 days fed a diet rich in AGS . Wistar rats (n=18) adults aged 90 days were fed either a control diet (CTL) or a diet rich in AGS (high-fat diet, HFD). The animals were divided into 3 groups: control group (CTL: n=6); group diet rich in AGS + probiotic formulation of L. fermentum 139, 263 and 296 (HFD-LF: n=6); High AGS diet group (HFD: n=6). The administration of L. fermentum strains (109 CFU/mL of each strain) was performed daily via gavage from the 90th to the 120th day of life. On the 120th day of life, feces were collected for analysis of fecal microbiota, blood samples were quantified total cholesterol (TC), high-density lipoprotein (HDL-cholesterol), low-density lipoprotein (LDL-cholesterol), triglycerides ( TG) and the insulin tolerance test (TII) was performed. Cardiovascular parameters were obtained from the recording of BP and heart rate (HR) at baseline levels and after administration of hexamethonium (a sympathetic nervous system ganglion blocker; dosage of 25mg/kg) to assess the contribution of sympathetic tone. The variability of HR and BP was evaluated under baseline conditions. The HFD-LF group had lower serum levels of TG, TC and LDL-cholesterol, higher plasma concentration of HDL-cholesterol and smaller area under the TII curve after receiving the treatment with the probiotic formulation of L. fermentum for 4 weeks, when compared to the HFD group (p<0.05). The BP levels were lower in the HFDLF group compared to the HFD group (p<0.05), but with no change in HR (p>0.05). In the spectral analysis, the probiotic formulation with L. fermentum prevented an increase in the LF oscillations of the systolic blood pressure (SBP) and the LH/HF ratio of the cardiac interval of the HFD-LF group (p<0.05) compared to the HFD group. However, the treatment did not interfere with HF oscillations and spontaneous baroreflex sensitivity compared to the HFD group (p>0.05). After administration of hexamethonium, the increase in vasomotor tone was prevented in animals from the HFD-LF group compared to the HFD group (p<0.05). Considering the composition of the intestinal microbiota, low richness and low diversity were found in the HFD-LF group in relation to the CTL. In the HFD group, the AGS-rich diet increased the relative abundance of bacteria that impair intestinal integrity, such as the Enterobacteriales and Campylobacterales orders, the Clostridiaceae, Peptostreptococcaceae families and showed a positive correlation with the Ruminococcus torques and Ruminococcus gnavus species, which also impair intestinal barrier function. In addition, the AGS-rich diet reduced the relative abundance of bacteria that favor intestinal integrity, such as the Lachnospiraceae families, other Ruminococcaceae species, Erysipelotrichaceae, and the orders Mollicutes RF39, Gastranaerophilales from the HFD group compared to the CTL group. After the administration of L. fermentum, a lower abundance of bacteria that affect the intestinal microbiome Campylobacterales, Helicobacteraceae and a negative correlation with Ruminococcus gnavus and Ruminococcus torques was found. A positive correlation was found with bacteria that strengthen the intestinal barrier, such as Ruminococcaceae_UCG-004. Treatment with L. fermentum probiotic formulation improved the composition of the intestinal microbiota, attenuated disorders in the lipid profile, prevented insulin resistance and sympathetic hyperactivity in rats fed a diet rich in AGS.