Metabolic disorders such as diabetes, metabolic syndrome or obesity, are a sign of our times. They are an outstanding consequence of our modern feeding behaviours, and their incidence has been steadily rising in the last few decades. Obesity can actually be considered a global epidemic - the World Health Organization estimates that worldwide, at least one billion adults are overweight and 300 million are obese, and the prevalence of obesity is also rapidly increasing in children.
These metabolic disorders are more than meets the eye. They have insidious consequences that in the long run can be significantly damaging. In fact, the rise in human obesity is closely linked to the increase in other chronic diseases such as cardiovascular disease, respiratory diseases, neurodegeneration, and certain cancers.
Diet is known to influence a number of physiological functions, namely the gut microbiota and immune system. The latter has an obvious impact on health, being our first line of defence, but the gut microbiota has also been gaining ground as a key commander of our health, both through its influence on the immune system and through its association to the brain via the gut-brain axis.
Metabolic disorders are mostly due to inadequate modern dietary patterns. Chronic low-grade inflammation is induced primarily as a consequence of modern lifestyles, be it through poor nutrition and nutritional overload, sedentarism, or stress. By being able to affect virtually all physiological processes, chronic low-grade inflammation is most likely the driving force of the many dysfunctions associated with metabolic disorders.
Diet and inflammation
Diet is regarded as the main contributor to chronic low-grade inflammation. There is a considerable amount of evidence indicating that many foods and food components can actively and chronically influence inflammation. In fact, the inflammatory trigger in obesity is indeed metabolic - an excessive intake of nutrients.
Under normal conditions, there is a low-level inflammation that peaks after feeding and is over after the nutrients are metabolised. But in conditions of overfeeding, there is a constant stimulus arising from nutrient intake that maintains the inflammatory response. These responses accumulate over time, are intensified with each nutrient exposure, and begin to affect other physiological functions. In contrast, fasting states have been linked to anti-inflammatory activity.
Due to the ability of fat-storing cells to produce and secrete inflammatory molecules, the adipose tissue can sustain metaflammation. Bad feeding habits and sedentary lifestyles lead to a massive increase in harmful adipose tissue. Weight gain can lead to functional changes in the adipose cells, thereby leading to an increased release of pro-inflammatory factors.
Fats are the most obvious example of the impact of diet on health. They may affect inflammatory processes through effects on body weight and on adipose cells’ structure and function. Research supports this view – studies have shown that the administration of fats to mice results in inflammatory responses. Likewise, studies in humans have shown that within hours after ingestion of a high-fat, high-carbohydrate meal, there is a significant increase in the circulating levels of oxidative and pro-inflammatory molecules. But while saturated fatty acids have pro-inflammatory effects, polyunsaturated fatty acids (such as omega-3 fatty acids) can increase the production of beneficial anti-inflammatory molecules. A low-fat omega-3 fatty acid-enriched diet can actually reduce the risk of developing metabolic syndrome.
Dietary carbohydrates are also key contributors to inflammation. High blood glucose levels contribute to diabetes along with other metabolic diseases, affecting cellular processes associated with oxidative stress and inflammation. Although it is still scarce, there is evidence indicating a positive correlation between the glycaemic index and low-grade inflammation. Diets low in glycaemic load and high in whole grains may have a protective effect against systemic inflammation, being able to reduce diabetes incidence in the long term by 50%.
By increasing the production of inflammatory molecules, diet can ultimately affect our brain’s health, as well as our mood and behaviour, having an outstanding impact on our quality of life. This stands in line with recent experimental data showing that a high-fat diet in mice induces depressive-like behaviours. Recent findings also indicate that an increased consumption of fruits and vegetables can improve memory, cognitive function and decrease the risk of age-related neurodegenerative diseases. Since these foods are rich in substances with strong anti-inflammatory properties, such as flavonoids, their effect may be attributed to a decrease in the overall inflammatory status.
Chronic low-grade inflammation and the gut microbiota
An important factor contributing to chronic low-grade inflammation is the gut microbiota. Recent evidence indicates that bad dietary patterns and obesity lead to noteworthy changes in the composition of the gut microbiota, specifically, a decline in the diversity of the bacterial composition of the gut.
Interactions between the microbiota and the gastrointestinal tract are known to influence immunity, protecting us against pathogens and contributing to the maintenance of gastrointestinal barrier integrity. Intestinal permeability is an important factor in our health - a healthy gut is designed to allow nutrients to pass into the bloodstream while keeping potentially harmful entities from invading our body.
Evidence shows that a high-fat diet can induce alterations in the gut microbiota and affect intestinal permeability leading to the diffusion of inflammatory molecules into the bloodstream. Consequently, widespread pro-inflammatory processes can occur, and this mechanism can partially account for the chronic low-grade inflammation observed in metabolic disorders.
Among the main pro-inflammatory substances produced by the gut microbiota are bacterial lipopolysaccharides. These are endotoxins that elicit strong inflammatory responses, being an important trigger for widespread low-grade inflammation, potentiating the development of metabolic diseases.
Accordingly, experimental studies using mice fed with a high-fat diet have shown that an increased gut permeability associated with increased levels of endotoxins in the blood could be a trigger for the development of diabetes. Most of those changes were reversed when the high-fat diet was supplemented with a prebiotic – a non-digestible ingredient that stimulates the growth and/or action of beneficial bacteria – highlighting the direct contribution of the gut microbiota to the development of metabolic disorders.
Weight loss has been shown to also be able to positively affect these outcomes, leading to beneficial changes in the intestinal microbiota content and to an improvement of the inflammatory profile of the adipose tissue.
Anti-inflammatory diet
Many of the effects described above can be reversed, or at least attenuated by dietary changes. Healthier feeding habits can decrease the stimuli that drive inflammatory responses. Experimental data has shown that weight loss alone can significantly attenuate chronic low-grade inflammation. By decreasing the amount of fat stored in adipose cells, weight loss decreases the release of detrimental pro-inflammatory mediators contributing to a decrease in metaflammation.
Thereby, a decrease the intake of pro-inflammatory foods such as processed foods, which have a high glycaemic load and a high saturated fat content is certainly helpful. Also, an increase the intake of foods rich in flavonoids and other polyphenols, particularly vegetables, fruits, berries, whole grains, and foods with high levels of omega-3 fatty acids, such as fish, nuts, and seeds, for example, will have an anti-inflammatory action, actively contributing to our general health.
Bad diet, sedentarism, stress, the gut microbiota, metabolic disorders, cardiovascular diseases, cognitive decline, depression, sleep disorders, pain, aging… It’s a long list of features, processes and conditions that are all connected by an insidious element: chronic low-grade inflammation. Modern lifestyles, particularly in developed countries, are slowly deteriorating our health. But it’s never too late to adopt healthier habits.
Credit
Sara Adaes is a biochemist with a PhD in neuroscience and with a keen enthusiasm for science communication.
Read Part 1: Chronic Low Grade Inflammation - A common ground for modern disease
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