Processed foods drive intestinal barrier permeability and microvascular diseases

One increasingly recognized and potentially pathogenic component of processed foods is a group of posttranslational modifications known as advanced glycation endproducts (AGEs). AGEs are generated from mixtures of amino acids and reducing sugars via the Maillard reaction that takes place under heat conditions such as during thermal processing, which commonly occurs during food production and processing. Because the Maillard reaction induces chemical changes within foods that impart flavor and aroma, the food industry has long enhanced or supplemented Maillard reaction products in foods to increase sensory properties and palatability, and as such, AGEs are a ubiquitous component of processed (and particularly extensively heat-treated) foods. The consumption of processed foods containing these AGEs may underlie chronic disease risk.

Most of the diet-derived AGEs escape digestion and absorption and pass through the gastrointestinal tract to the colon. Here, they are available as substrates for gut microbial metabolism. However, the extent to which long-term intake of processed food impacts intestinal permeability and influences the outcome of microvascular disorders such as CKD is unclear. Consumption of processed foods has been linked to cancer, cardiovascular diseases, and all-cause mortality; thus, there is an urgent need to define the molecular mechanisms linking chronic intake of processed foods to the onset and progression of non-communicable diseases.

Abstract:

“Intake of processed foods has increased markedly over the past decades, coinciding with increased microvascular diseases such as chronic kidney disease (CKD) and diabetes. Here, we show in rodent models that long-term consumption of a processed diet drives intestinal barrier permeability and an increased risk of CKD. Inhibition of the advanced glycation pathway, which generates Maillard reaction products within foods upon thermal processing, reversed kidney injury. Consequently, a processed diet leads to innate immune complement activation and local kidney inflammation and injury via the potent proinflammatory effector molecule complement 5a (C5a). In a mouse model of diabetes, a high resistant starch fiber diet maintained gut barrier integrity and decreased severity of kidney injury via suppression of complement. These results demonstrate mechanisms by which processed foods cause inflammation that leads to chronic disease.”

The study found that regularly eating foods cooked or processed at high temperatures causes a component of the innate immune system to become hyperactive, injuring the kidneys after feeding rats either standard chow or a heat-treated diet for 24 weeks to gain a better understanding of how long term consumption impacts intestinal permeability.

Rats on the heat-treated diet experienced fivefold higher leakage of albumin into their urine, indicating kidney damage, and they showed signs of early chronic kidney disease including an increase in tubulointerstitial fibrosis and changes to a tuft of capillaries involved in blood filtration, compared to the controls. A drug containing alagebrium chloride AGE pathway inhibitor was fed to the rats which resulted in improvements in kidney injuries and related health problems, indicating that AGEs may be behind the changes observed.

It was also noted that the presence of complement component C3 was found exclusively in the animals on the heat-treated diet, this protein is part of the innate immune complement system that is activated by invading pathogen or tissue injury. 

“These studies support the notion that chronic consumption of processed foods negatively affects renal health via changes in the gastrointestinal ecosystem. Fermentation of complex carbohydrates, proteins, and fats that reach the lower gastrointestinal tract by the gut microbiota results in the synthesis of a multitude of metabolites that can act both locally and systemically, and the digestibility of proteins by the host is influenced, in part, by food processing,” write the authors. 

“We can make alternative food formulations or functional foods aimed at dampening the response due to eating processed foods,” says Melinda Coughlan, corresponding author for this study. “For example, we can add resistant starch into processed foods, which would support growth of beneficial bacteria in the gut and protect from inflammation. Nevertheless, the dietary advice would be to reduce the intake of highly processed foods.”