Effect Of Fecal Microbiota Transplantation On Glucose And Lipid Metabolism In Mice

Backgrounds The gut microbiota plays an important role in human physiology and health,and has become one of the research hotspots in recent years.Dysregulation of the gut microbiota is a common feature of obesity and metabolic diseases,studies including humans and mice have confirmed that the gut microbiota of obese and diabetic patients has reduced diversity and reduced gene abundance,but the mechanism and the causal relationship have not yet been clarified.As a new method of disease prevention and treatment,fecal microbiota transplantation,its achievements in the treatment of Clostridium difficile infection have given the medical community more expectations for its application value.However,the research data of fecal microbiota transplantation in metabolic diseases,such as diabetes,is still very limited.Purpose In this study,db/db mice with type 2 diabetes and normal C57BL/6J mice were treated with fecal microbiota suspension from normal C57BL/6J mice and non-interfered db/db mice,by gavage respectively.To observe the effects of fecal microbiota transplantation on glucose and lipid metabolism and islet morphology,as well as the changes of fecal microbiota after intervention,so as to provide partial experimental basis for exploring the application of fecal microbiota transplantation in the treatment of type 2 diabetes.Methods16 male db/db mice aged 6-7 weeks were randomly divided into diabetic control group(group DC)and diabetic fecal microbiota transplantation group(group DF),16 male C57BL/6J mice aged 6-7 weeks were randomized divided into normal control group(group NC)and normal fecal microbiota transplantation group(group NF),each group has 8mice.The mice in the DF group received the fecal microbiota suspension from the mice in the NC group by gavage,and the mice in the NF group were gavaged with faecal bacteria suspension from the DC group.The mice in the DC group and the NC group were given the same amount of normal saline by gavage.The intervention lasted for 12 weeks,once a day,200ul/mouse.In this period,the physiological,biochemical and glucose metabolism indexes were monitored continuously in each group.Feeding until 24 weeks,the intervention is over.Serum samples were taken to analyze the glycolipid and inflammatory indexes.The tissues of pancreas and liver were taken for histochemical staining to observe the morphological structure of the tissues.The number of pancreatic islets and the distribution of β-cells were observed by immunofluorescence staining.Fecal samples were used to analyze the composition of the microflora by 16 S amplicon sequencing.Results1.Mice in DF group had reduced food intake and body weight.2.Compared with DC group,FMT significantly reduced fasting blood glucose and improved insulin sensitivity in DF group.3.In the DF group,the islet area and the proportion of β cells was increased,the number of islets was increased to some extent.4.The serum TC and TG levels of DF group were significantly decreased.5.FMT decreased serum TNF-α and IL-1β level in DF group,but the difference was not statistically significant.6.FMT altered intestinal microbiota structure of DF group mice,increased the abundance of butyric acid-producing bacteria such as Clostridium at the species genus levelConclusions FMT from normal donors altered intestinal microbiota structure,improved glucose and lipid metabolism,increased islet area and β-cell ratio in diabetic mice.