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The human gut microbiome is a complex ecosystem of trillions of microorganisms that play a crucial role in maintaining various aspects of health, including cardiometabolic health. Keep reading to learn about how dysbiosis, metabolic endotoxemia, short-chain fatty acids (SCFAs), and specific microbial species can contribute to cardiometabolic conditions.

How the microbiome influences cardiovascular health

The gut microbiome influences cardiovascular health through multiple pathways, including the modulation of lipid metabolism, regulation of blood pressure, and modulation of inflammatory processes. Beneficial gut bacteria produce metabolites, such as SCFAs, that help regulate lipid profiles and glucose metabolism, thereby playing a protective role against cardiovascular diseases (CVD). (Rahman 2022)

One significant aspect of this influence is the production of trimethylamine N-oxide (TMAO), a compound derived from dietary choline and L-carnitine, which are abundant in red meat and other animal products. In the presence of certain gut bacteria, these nutrients convert into trimethylamine (TMA), which the liver then converts into TMAO. Elevated levels of TMAO have been linked to increased risk of atherosclerosis and other cardiovascular conditions. (Rahman 2022)

Cardiometabolic health is intricately linked with the gut microbiome. 

Dysbiosis and cardiometabolic disease

Dysbiosis, an imbalance in the composition of gut microbiota, is closely linked to the development of cardiometabolic disease. (Rahman 2022) When harmful bacteria outnumber beneficial ones, it disrupts the gut barrier function, leading to increased intestinal permeability. This "leaky gut" allows toxins, such as lipopolysaccharides (LPS), to enter the bloodstream, triggering systemic inflammation—a key factor in the pathogenesis of cardiometabolic disease. (Mohammad 2021)

Metabolic processes, inflammation, and immune function

Gut microbiota play a pivotal role in metabolic processes by influencing energy harvest from the diet, regulating glucose metabolism, and modulating lipid profiles. For example, beneficial bacteria ferment dietary fibers to produce SCFAs like acetate, propionate, and butyrate, which have systemic metabolic effects. These SCFAs positively affect gastrointestinal (GI) integrity, enhance insulin sensitivity, reduce inflammation, and regulate lipid metabolism, thereby contributing to metabolic health. (Tang 2021)

Inflammation and immune function are also significantly impacted by the gut microbiota. Beneficial microbes help maintain a balanced immune response, preventing chronic inflammation, which is a hallmark of many metabolic disorders. Dysbiosis, on the other hand, can lead to an overactive immune response, contributing to chronic inflammation and the progression of cardiometabolic disease. (Fakharian 2023)

Metabolic endotoxemia

Metabolic endotoxemia, characterized by elevated levels of LPS in the bloodstream, is a consequence of dysbiosis and increased intestinal permeability. LPS, a component of the outer membrane of Gram-negative bacteria, is a major trigger of systemic inflammation. When LPS enters the bloodstream, it activates the immune system, leading to the production of pro-inflammatory cytokines. Chronic exposure to LPS-induced inflammation is a critical factor in the development of insulin resistance, atherosclerosis, and other cardiometabolic diseases. (Mohammad 2021)

SCFAs

SCFAs are produced by beneficial gut bacteria through the fermentation of dietary fibers and play a vital role in maintaining metabolic health. These fatty acids, particularly acetate, butyrate, and propionate, have several beneficial effects:

• Acetate: Serves as a substrate for lipid synthesis and regulates appetite (Hernandez 2019)

• Butyrate: Promotes gut barrier integrity, reduces inflammation, and improves insulin sensitivity (Van Deuren 2022)

• Propionate: Reduces hepatic gluconeogenesis, thereby lowering blood glucose levels (Yoshida 2019)

Overall, SCFAs enhance glucose metabolism, reduce inflammation, and improve lipid profiles, which collectively protect against cardiometabolic disease. Dysbiosis can impact SCFA production, inhibiting the protection that these fatty acids offer. (Tang 2021)

Symptoms and conditions associated with microbiome-related imbalances

Imbalances in the gut microbiome are associated with a range of symptoms and conditions, including:

• Cardiovascular conditions: Hypertension, atherosclerosis, and heart failure (Rahman 2022)

• Gastrointestinal symptoms: Bloating, diarrhea, constipation, and abdominal pain (Menees 2018)

• Immune dysfunction: Increased susceptibility to infections and autoimmune conditions (Wang 2024)

• Metabolic disorders: Obesity, insulin resistance, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) (Rahman 2022)

• Systemic inflammation: Chronic low-grade inflammation contributing to cardiometabolic disease (Rahman 2022)

When assessing cardiometabolic disease risk, start by identifying these symptoms or conditions that may indicate the need for a closer look into the microbiome.

Gastrointestinal symptoms like bloating, diarrhea, abdominal pain, and constipation may be a sign of microbiome imbalance. 

Microbiome testing

Multiple studies have found that people with both obesity and diabetes have increased numbers of Gram-negative bacteria, along with an abnormal release of LPS, which causes an increase in intestinal permeability and endotoxemia. (Marzullo 2020) Dietary patterns that improve the microbial environment can reduce the negative impact of dysbiosis. (Richardson 2022) Several clinical trials have also found that supplementation with various probiotics and prebiotics may help reduce body mass index (BMI), blood pressure, and leptin levels (a hormone that plays a role in energy regulation and appetite levels). (Asadi 2022)

A study examining chronic heart failure found that patients had an increased number of pathogenic bacteria and Candida species in the gut, along with increased intestinal permeability, which was associated with the severity of their heart failure. (Pasini 2016) Another study on coronary artery disease (CAD) found that patients had significantly increased levels of Lactobacillales and significantly decreased levels of the phylum Bacteroidetes. (Yamashita 2016)

While several microbial species have been associated with cardiometabolic health, two in particular have been linked to adverse metabolic outcomes. Akkermansia muciniphila is known for its role in maintaining gut barrier integrity and anti-inflammatory properties. Lower levels are associated with obesity, diabetes, and metabolic syndrome. (Rodrigues 2022) Faecalibacterium prausnitzii is a major butyrate producer with anti-inflammatory effects. Reduced levels are linked to inflammatory bowel diseases and metabolic disorders. (Lenoir 2020)

Key markers

Given the critical role of the gut microbiome in health and disease, microbiome testing is an essential tool. It provides insights into the composition and function of a patient’s gut microbiota, helps identify imbalances, and guides personalized treatment plans. In addition to assessing the microbial environment, here are some additional markers that can provide useful insights.

Calprotectin

Calprotectin is a marker of gut inflammation and is often elevated in patients with cardiometabolic disease. Analyzing calprotectin levels through stool testing can provide insights into intestinal health. (Heinzel 2024)

SCFAs

Dysbiosis can impact SCFA production, leading to poor glucose metabolism, increased inflammation, and dysregulated lipid levels. Measuring levels of SCFAs in stool samples can indicate the metabolic activity of gut bacteria and overall metabolic health status. (Besten 2013)

Zonulin

Elevated zonulin levels, often associated with cardiometabolic diseases, are linked to gut inflammation. Measuring zonulin levels in blood or stool provides an indicator of intestinal permeability and gut barrier function. (Ohlsson 2017)

Secretory immunoglobulin A

Secretory Immunoglobulin A (sIgA) is an important marker of gut mucosal immunity, protecting the gut lining and promoting the growth of beneficial bacteria. In the context of cardiometabolic health, low levels of sIgA may indicate compromised mucosal immunity, leading to increased intestinal permeability and contributing to systemic inflammation—a key driver of cardiometabolic diseases. (Mantis 2011)

TMAO

TMAO is a critical link between the gut microbiome and cardiovascular health. Elevated TMAO levels are associated with an increased risk of atherosclerosis and adverse cardiovascular events. Since TMAO is produced by gut bacteria from dietary nutrients, measuring TMAO levels in the blood can provide insights into the metabolism of dietary nutrients by gut bacteria. (Rahman 2022)

For further information on lab test options for microbiome and cardiometabolic health, view Fullscript’s microbiome testing guide here.

The microbiome as an indicator of cardiometabolic health

The gut microbiome plays a central role in cardiometabolic health, influencing cardiovascular health, metabolic processes, inflammation, and immune function. Dysbiosis and increased intestinal permeability are key contributors to cardiometabolic disease. Understanding the intricate relationships between gut microbiota and cardiometabolic health, as well as leveraging microbiome testing options, is crucial for developing targeted treatment plans to help prevent and manage these conditions.