The human microbiome refers to the trillions of microorganisms that live in and on our bodies. While microbes are present throughout the body, the gut contains the highest concentration, with around 38 trillion bacteria, fungi, viruses and other microbes residing in the colon. This “gut microbiome” plays a critical role in human health and disease, including metabolism.
What is Metabolism?
Metabolism refers to all of the biochemical reactions that occur within the body to sustain life. This includes breaking down food into energy, regulating blood sugar levels, metabolizing fats, and much more. Key measures of metabolic health include:
- Energy balance and body fat percentage
- Blood glucose control and insulin sensitivity
- Blood lipid levels like cholesterol and triglycerides
Poor metabolic health is extremely common, with around 75% of American adults being overweight or obese. Rates of diabetes, fatty liver disease and heart disease are also very high. Optimizing metabolism is critical for reducing risk of chronic diseases.
How the Gut Microbiome Influences Metabolism
The gut microbiome can influence metabolism in several key ways:
Regulating Appetite and Energy Balance
TThe composition and diversity of the gut microbiome plays an instrumental role in appetite regulation and overall energy balance. The microbes communicate with appetite-regulating hormones, ultimately influencing how hungry we feel and how much we eat.
Specifically, the gut microbes ferment dietary fiber to produce short-chain fatty acids like butyrate, propionate and acetate. These short-chain fatty acids can bind to receptors in the colon, stimulating the release of key satiety hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).
GLP-1 activates areas of the brain that control food intake, suppressing appetite. It also slows gastric emptying, prolonging feelings of fullness after eating. PYY acts on receptors in the gut and brain to increase satiety. Studies show that higher fiber intakes boost GLP-1 and PYY levels, enhancing post-meal satiety.
For example, in one trial, people felt more satiated and less hungry after eating a high fiber bean burger compared to an animal-based cheeseburger with the same calories. The bean burger meal stimulated much greater release of GLP-1 and PYY.
By increasing satiety hormones, the gut microbiome andfiber help prevent overeating. This regulates energy balance and reduces calorie intake, which can prevent weight gain and obesity. Population studies have found fiber intake is inversely associated with body mass index, with vegans having the lowest BMIs and highest fiber intakes.
Clinical trials also demonstrate increased satiety and weight loss with higher fiber intakes. Optimizing the gut microbiome with prebiotics and a diverse array of plant foods is a powerful tool for controlling appetite, achieving sustainable weight loss and maintaining healthy body weight over the long-term.
Influencing Fat Storage and Burning
The gut microbiome and its byproducts play an important role in determining whether our bodies are primarily storing fat or burning it for energy.
Short-chain fatty acids appear to stimulate breakdown of fat by activating brown adipose tissue. Brown fat is a special type of metabolically active fat that generates heat by burning calories. This allows short-chain fatty acids to increase energy expenditure.
Animal studies also indicate short-chain fatty acids may block uptake of fatty acids into adipocytes (fat cells) and muscle cells. This inhibits fat accumulation in these tissues. Fatty acids that cannot be stored end up circulating in the bloodstream and get metabolized for energy instead.
Additionally, short-chain fatty acids strengthen the intestinal barrier by improving tight junctions between gut epithelial cells. When gut permeability is increased, inflammatory compounds like lipopolysaccharide (LPS) can leak out into circulation. This drives inflammation and can lead to insulin resistance, which promotes fat storage. By enhancing the gut barrier, short-chain fatty acids protect against inflammation and insulin resistance.
Clinical studies in humans show people who consume more fiber lose significantly more body fat compared to low fiber intakes, even when both groups eat the same number of calories. For example, in one trial individuals lost more fat mass over two weeks on a high fiber, plant-based diet versus a low fiber, animal-based ketogenic diet while eating ad libitum.
In summary, by stimulating brown fat, blocking fat uptake into cells, reducing inflammation and insulin resistance, and enhancing satiety, the microbiome and its short-chain fatty acid products facilitate a metabolic shift from fat storage to fat burning. This has major implications for obesity, metabolic syndrome and related chronic diseases.
Improving Blood Sugar Control
The gut microbiome plays a central role in glucose metabolism and insulin sensitivity. Optimizing the composition and function of the gut microbes can be a powerful tool for improving blood sugar regulation.
Short-chain fatty acids like butyrate improve insulin sensitivity by increasing glucose uptake in muscle and fat cells. They activate glucose transporters, like GLUT4, that allow glucose to move from the bloodstream into tissues where it can be used for energy.
Short-chain fatty acids also stimulate the release of insulin from pancreatic beta cells. They do this by binding to receptors that trigger secretion of the incretin hormone GLP-1. GLP-1 goes to the pancreas and stimulates insulin secretion in a glucose-dependent manner.
Studies indicate short-chain fatty acids reduce glucose production in the liver as well. This prevents excessive release of glucose into the bloodstream, which helps control blood sugar spikes after meals.
Clinical trials in diabetics have found that increasing fiber intakes alters the gut microbiome in ways that increase short-chain fatty acid production. This is accompanied by elevations in GLP-1 and significant improvements in glucose control and insulin sensitivity within weeks.
For example, one study found that a high fiber, prebiotic diet lowered hemoglobin A1c substantially more than a standard diabetic diet over 12 weeks. Transplanting the microbiome from the high fiber group into mice replicated the beneficial effects.
Population studies also show inverse associations between dietary fiber intake and type 2 diabetes risk. Each 10 gram increase in daily fiber is linked to a nearly 10% reduction in diabetes risk.
In summary, by enhancing insulin sensitivity, suppressing glucose release from the liver, stimulating insulin secretion and slowing gastric emptying, the microbiome-derived short-chain fatty acids play a pivotal role in optimizing glycemic control and preventing diabetes.
Optimizing Blood Lipid Levels
The gut microbiome influences several aspects of lipid metabolism and can help optimize blood cholesterol and triglyceride levels when nourished with adequate fiber.
One of the primary mechanisms fiber improves cholesterol levels is by binding to bile acids in the intestines. Bile acids are made from cholesterol by the liver to help absorb dietary fats. When fiber binds bile acids, it increases their excretion in feces.
To replace the lost bile acids, the liver has to pull LDL cholesterol out of circulation to synthesize more. This lowers serum LDL cholesterol concentrations. Soluble fibers like beta-glucan from oats and pectin from fruit are particularly effective at this.
In addition, short-chain fatty acids inhibit cholesterol synthesis by the liver. They suppress gene expression of key enzymes involved in endogenous cholesterol production. This provides a one-two punch – increasing bile acid excretion while simultaneously reducing cholesterol synthesis.
Just 5 grams per day of soluble fiber consumption has been shown in meta-analyses to significantly reduce LDL cholesterol. This degree of reduction is estimated to lower heart disease risk by 10%.
The gut microbiome also plays a role in regulating levels of triglycerides – the major form of fat in the blood after meals. Clinical studies indicate the composition of the gut microbiome is one of the strongest predictors of postprandial triglyceride response, even stronger than age, BMI or genetics.
Overall, optimizing the gut microbiome with prebiotics like fiber is a powerful tool for improving cholesterol particle profiles and triglyceride levels. This has major implications for reducing cardiovascular disease, which is the leading cause of death worldwide.
Proof it Works in Humans
While these mechanisms are supported by a wealth of research, do higher fiber intakes actually improve metabolic health in humans? The answer is a resounding yes. Large systematic reviews and meta-analyses consistently show that people who eat more fiber have:
- Lower body weight
- Reduced risk of type 2 diabetes
- Less heart attacks and cardiovascular death
- Decreased risk of stroke
- Lower rates of colorectal, breast and esophageal cancers
In one major analysis of over 120 million person-years of data, each 10 gram increase in fiber intake was associated with a 10% decrease in heart disease and stroke risk. Notably, higher fiber intakes are linked to living significantly longer lives.
Conclusion – benefits for metabolic health
Optimizing the gut microbiome by consuming a diverse array of high-fiber plant foods provides immense benefits for metabolic health. By nourishing our gut bacteria, fiber enhances satiety hormones, improves fat burning, increases insulin sensitivity, lowers cholesterol and much more. While more research is still needed, studies clearly demonstrate that higher intakes of fiber improve several key markers of metabolism and reduce risk of obesity, diabetes, fatty liver disease and cardiovascular disease.
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