Obesity is a global health concern with rising prevalence and is associated with various metabolic diseases, including type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), and cardiovascular diseases. Current treatments for obesity, such as bariatric surgery and weight-loss drugs, have limitations and potential health risks. Fecal microbiota transplantation (FMT) is being explored as an innovative method for restoring gut microbiota diversity and balance, potentially impacting weight management and related metabolic conditions. This article examines the research on FMT and its effects on weight loss, blood glucose management, and associated metabolic diseases.
Understanding Obesity and Its Challenges
Obesity, characterized by excessive triglyceride accumulation, is more than just weight gain; it significantly impacts quality of life and poses serious health risks. The World Health Organization Statistics indicate a global rise in obesity, with nearly 2.1 billion adults overweight and over 700 million obese by 2017. Obesity is associated with metabolic diseases, such as type 2 diabetes, heart disease, and NAFLD, making effective treatments crucial.
Limitations of Current Weight-Loss Methods
While bariatric surgery can effectively reduce weight and metabolic diseases, it is invasive and carries a high rate of illness and death. It also alters the secretion of ghrelin, bile acids, and gut hormones, affecting the central prefrontal cortex and dopaminergic signaling pathways, potentially increasing sensitivity to other rewards like alcohol. Weight-loss drugs, primarily appetite suppressants, can cause adverse reactions like pain, insomnia, anxiety, and gastrointestinal issues, with a high relapse rate after withdrawal.
Fecal Microbiota Transplantation (FMT): An Overview
FMT involves transplanting fecal microbiota from a healthy donor to a recipient to restore gut microbiota diversity and balance. The process typically involves strict donor screening, intestinal preparation using antibiotics or laxatives, and transplantation via oral coprofecal capsules, upper or lower gastrointestinal tract routes. Colonoscopy is a common approach, and FMT can be repeated in initial non-responders.
FMT in Treating Various Conditions
FMT was first successfully used in children with Clostridioides difficile infection (CDI) in 2010. The Food and Drug Administration included FMT in its treatment guidelines for recurrent CDI in 2013. FMT is also being explored for treating metabolic diseases, allergic diseases, autism spectrum disorders, and other extra-intestinal diseases.
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FMT and Metabolic Diseases: Exploring the Connection
Microbiome dysbiosis has been linked to gut flora control, contributing to type 2 diabetes, NAFLD, and obesity. Researchers have been exploring the potential use of FMT in treating metabolic conditions like obesity. A meta-analysis examined how FMT affects weight and glycemic management in individuals with NAFLD, T2DM, and related metabolic disorders to enhance clinical therapy.
Meta-Analysis of FMT's Impact on Weight and Blood Glucose
The meta-analysis included studies published up to October 2022, focusing on FMT's effects on weight and glycemic management in obesity and related metabolic conditions. The analysis excluded studies with repeated publications, incomplete information, or those impossible to extract data from, as well as case reports, reviews, and systematic reviews.
Key Findings
Pooled outcomes from the meta-analysis revealed that weight levels, BMI levels, HOMA-IR, and HbA1c were significantly lower after FMT treatment compared to before treatment. Specifically, the weighted mean difference (WMD) for weight was -4.77 (95%CI: -7.40~-2.14), for BMI was -1.59 (95%CI: -2.21~-0.97), for HOMA-IR was -0.79 (95%CI: -1.57~-0.00), and for HbA1c was -0.65 (95%CI: -0.75~-0.55). However, FMT treatment may not significantly affect glucose and insulin levels in obese patients at fasting and related metabolic diseases. Subgroup analysis indicated that FMT significantly reduced fasting blood glucose in people with diabetes.
Study Characteristics
The meta-analysis included six publications with a total of 130 patients (92 males and 38 females). Three trials included patients from the United States, and three included participants from China. The average age range was 42.5 to 57.3 years, and average fasting blood glucose concentrations ranged from 5.19 to 8.5.
Analysis of Weight and BMI
Three studies involving 67 patients examined the weight of individuals with obesity and metabolic disorders. A fixed effects model was employed due to minimal heterogeneity (I2 = 7.1%, p = 0.341). Four investigations (105 patients) examined the BMI of obese individuals and associated metabolic illnesses, also using a fixed effects model due to low heterogeneity (I2 = 38.5%, p = 0.181).
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Fasting Blood Sugar Levels
Three studies (114 patients) looked at fasting blood sugar levels in people with obesity and related metabolic diseases. Sensitivity analysis revealed that the study by Ding et al. significantly impacted the outcomes due to the inclusion of diabetic populations, while other studies included normal glycemic populations. After excluding Ding et al.'s study, heterogeneity was significantly reduced (I2 = 0.0%, p = 0.662), and a fixed effects model was used.
Insulin Resistance
Two research studies (91 patients) examined how fasting insulin affected obesity and other metabolic illnesses. A fixed effect model was utilized due to no discernible heterogeneity (I2 = 0.0%, p = 0.321). The HOMA-IR in obesity and associated metabolic disorders was observed in two investigations (59 patients), and a fixed effects model was employed due to minimal heterogeneity (I2 = 0.0%, p = 0.453). Two studies (28 patients) reported the HbA1c in obesity and related metabolic diseases after FMT, and a fixed effects model was used due to minimal heterogeneity (I2 = 0.0%, p = 0.417).
Sensitivity Analysis
Sensitivity analysis revealed that the study by Ding et al. significantly impacted the analysis of fasting blood glucose. However, other studies showed stability and reliability in their outcomes.
Recent Studies and Findings
FMT and Weight Loss: A Randomized Clinical Trial
A randomized clinical trial involving 41 patients treated at two bariatric surgery centers in Finland found no significant differences in weight loss between patients receiving FMT from a lean donor versus their own fecal microbiota six months before obesity surgery. This double-blinded, placebo-controlled, multicenter trial was conducted from 2018 to 2021 with an 18-month follow-up.
Study Design
Patients eligible for bariatric surgery were recruited and randomized to receive either FMT from a lean donor or an autologous placebo via gastroscopy into the duodenum. Six months after FMT, most patients underwent LRYGB (Roux-en-Y gastric bypass) or LSG (laparoscopic sleeve gastrectomy).
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Key Results
The percentage of total weight loss at 6 months was 4.8% in the FMT group and 4.6% in the placebo group, with no significant difference between the groups. FMT did not affect presurgical and postsurgical weight loss. The study concluded that FMT alone is not sufficient to decrease body weight in humans.
Impact on Body Composition and Blood Chemistry
The reduction in mean BMI from baseline to the end of follow-up was significant in both groups, but no significant differences were observed between the groups. Similarly, the percentage of excess BMI loss was comparable between the groups. While fat percentage and visceral fat content increased marginally in both groups in the short term, they decreased postoperatively. Fasting glucose levels decreased in both groups, and uric acid levels decreased in the FMT group.
Safety and Tolerability
No complications related to the FMT procedures were reported. The patients were not under deep sedation, the transplant was infused deep into the duodenum, and the patients were asked to return to an upright position after the procedure to prevent reflux of the fecal transplant.
Emerging Research and Future Directions
The Role of Gut Microbiome in Obesity
Researchers are increasingly focused on understanding the role of the gut microbiome in metabolically healthy people with obesity. Animal models have shown that obese mice can be made lean and lean mice obese by changing their gut microbiota. Previous human trials of FMT transplant have shown improvement in insulin resistance in the liver in patients with metabolic syndrome.
Donor and Recipient Factors
Factors affecting FMT outcomes in subjects with obesity are being investigated. Donor factors, recipient factors, and the frequency of FMT are likely to affect treatment outcomes. Studies comparing mixed-donor nonintensive FMT and single-donor intensive FMT have shown durable increases in donor-derived species in intensive FMT.
Potential Risks and Considerations
While FMT is considered safe overall, the long-term effects are still unknown. Possible short-term side effects include abdominal pain, bloating, gas, constipation, diarrhea, bloody stools, nausea, fever, and worsening GI disorder symptoms. Long-term adverse effects may include obesity, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). There are also concerns about the risk of drug resistance and other microbiota-related conditions, such as diabetes.
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