Several studies have demonstrated a potential link between ultra-processed foods (UPF) and chronic inflammation. One recent review published in The Lancet Gastroenterology & Hepatology describes the mechanistic association between the consumption of UPF and chronic medical conditions, especially those involving the gut microbiome.

Study: Ultra-processed Foods and Human Health: From Epidemiological Evidence to Mechanistic Insights. Image Credit: Dawid Rojek / Shutterstock.com

Introduction

Many techniques have been developed for processing food over the past several centuries to preserve food and enhance its taste and digestibility. Modern industrially processed foods exploit the availability of salt, sugar, vegetable oils, animal fat, and flour.

Typically, the production of these products utilizes mechanical and physical techniques such as roller milling, extrusion, and pressure rendering, as well as chemical methods like hydrogenation. Artificial flavoring agents and preservatives, anticaking agents, and other additives are also used to achieve the final desired texture, color, and taste of these food products.

“These techniques allowed large-scale production and manufacturing of massively produced processed foods, making them available throughout the year.”

Such highly processed foods are typically hygienic, convenient, affordable, and accessible, thereby making them ideal products for many high-income countries (HIC). More recently, low- and middle-income countries (LMIC) have also become increasingly dependent upon these food products.

Coincident with this trend, there has been an increase in the number of chronic inflammatory cases, including metabolic syndrome and inflammatory bowel disease (IBD). The current paper explores the evidence for a correlation between modern UPFs and chronic disease that is mediated by the gut microbiota.

Types of processed foods

There are several classification systems used to describe foods based on their processing. The most commonly used is NOVA, which categorizes foods into groups 1 through group 4.

Group 1 includes unprocessed or minimally processed foods, such as fresh, chilled, dried, frozen, fermented, or pasteurized products. Group 2 consists of processed ingredients like vegetable oils, sugar, salt, butter, or other food extracts added to group 1 foods.

Group 3 includes all typical processed foods, such as salted canned foods, candied dry fruits, salted meats, cheeses, and fresh bread. In short, group 3 describes group 2 products added to group 1 foods.

Group 4 includes UPFs that have undergone one or more of the aforementioned industrial processes. These may contain non-domestic ingredients, including those used for flavoring, coloring, sweetening, or emulsification.

UPF intake has increased HICs, wherein they account for up to 30%, 50%, and almost 60% of caloric intake in France, the United Kingdom, and the United States, respectively.

Study findings

Almost 50% of the 100 prospective studies analyzed in the current study examined the association between UPFs and various health or mortality outcomes.

Mortality

Seven studies indicated a link between UPFs and death from any cause, with an increase in risk from 20% to 60% in the highest UPF intake category as compared to the lowest. Five studies showed an increased risk of illness or death from cardiovascular disease or stroke. Four studies showed a higher risk of type 2 diabetes, whereas one reported an increased risk of gestational diabetes.

Hypertension

Four studies reported an increased risk of hypertension by up to 30%, one with cancer risk, and several with overweight and obesity. Many of these studies also reported an association with increased weight, waist circumference, and increased serum lipid levels in children.

IBD

In the 2021 Prospective Urban Rural Epidemiology (PURE) study, UPF intake was associated with a higher risk of IBD, specifically for Crohn’s disease but not ulcerative colitis. Other studies have linked UPF consumption to an increased risk of depression, abnormal lipid levels, a decline in kidney function, and fatty degeneration of the liver.

Weight gain

Short-term randomized intervention trials are currently being conducted, wherein UPFs and unprocessed foods are assigned to different cohorts for short periods. Following this, the researchers observed increased energy intake by an average of over 500 kcal per day and a mean weight gain of 0.8 kg in the UPF group. Conversely, an average weight loss of over 1 kg was reported in the unprocessed food cohort. 

The mechanisms behind chronic inflammation with UPFs

There are numerous mechanisms that can be attributed to the weight gain and chronic inflammation observed with higher UPF consumption. One example includes the poor nutritional quality of many UPFs.

According to the French Open Food Facts database, only one in five UPFs had a high nutritional score. Even when the energy intake from UPFs is standardized for the sake of comparison with unprocessed foods, the adverse health outcomes continue to show a strong association, thereby indicating that “factors beyond nutritional aspects have a role.”

Another issue is the presence of potentially toxic substances in UPFs, such as polycyclic aromatic hydrocarbons, furans, advanced glycation end products, trans fatty acids from the hydrogenation of fats, and acrylamide from the cooking of starchy foods at high temperatures. The latter chemical can be found in common foods like French fries, crisps, and biscuits, whether made at home or industrially; however, acrylamide levels are often higher in these industrial products.

Other contaminants such as phthalates, bisphenols, mineral oils, and microplastics can leach into foods from the packaging, especially when the food remains in contact for long periods. This likely occurs in food products that are shelf-stable for extended durations.

Ready-to-eat meals are typically UPFs and require microwave heating, which may enhance the leaching of bisphenols from polycarbonate packaging or increase acrylamide formation.

The outcome of such exposures is unknown; however, prior research suggests a link with cancer, cardiovascular diseases, insulin resistance, type 2 diabetes, obesity, and endocrine aberrations.

Another issue is the structural change that arises in the various components of a food product due to processing, which could impact its bioavailability through altered digestibility, satiety, rate of eating, and chewing, all of which may contribute to the increased energy intake with UPFs. This area is severely under-researched.

Over 300 food additives are permitted in Europe, of which several may be implicated in chronic inflammation, perhaps through their effects on the gut microbiome. Landmark studies have established that dietary patterns influence gut microbiota profiles, which can subsequently alter host metabolism and promote obesity.

Gut bacteria are often capable of ingesting and processing simple sugars when exposed to high dietary fat. Intestinal stressors include certain food colorants, emulsifiers, artificial sweeteners, and nanoparticles like E171 (titanium dioxide).

These additives alter the ratio of key bacterial genera in the gut, wherein they affect the protective mucosal layer and expression of important defensive molecules like ­β-defensins, as well as allow microbes to reach the sterile zone of the mucosa. This triggers endotoxin accumulation that subsequently leads to metainflammation and IBD.

Simultaneously, changes in the molecular profile promote increased energy extraction from ingested foods, thus causing metabolic dysregulation and obesity.

This links caloric extraction from the food eaten to metabolic aberrations induced by the diet. This dysregulated metabolism is marked by low-grade inflammation and changes in the gut microbiome. The outcome is a leak of bacterial products like lipopolysaccharides (LPS) from the gut into the host system.

LPS from Gram-negative bacterial cell walls contain lipid A, which is a molecule that crosses the gut mucosa. Once lipid A reaches the blood, it can trigger inflammation of various target tissues like the liver and fatty deposits of the body.

This cycle has been referred to as “metainflammation.” Metainflammation can be defined as a metabolic inflammatory state defined by low-grade chronic inflammation created by metabolic cells and stress sensors.

This suggests the need for interventions in UPF intake to produce a beneficial change in the gut microbiome that will promote the production of ‘good’ bacterial metabolites through appropriate gene expression by gut mucosal cells. These include anti-inflammatory short-chain fatty acids (SCFAs).

Conclusions

The study findings emphasize the need for improving the current understanding of how food processing affects human health. Large-scale studies will be needed to identify components causally linked to metainflammation and obesity.

Public education is also crucial to support the consumption of healthier foods, preferably those that are minimally processed and without additives. Such dietary choices are emphasized by the United Nations Food and Agriculture Organization (FAO) recommendations, as well as several national dietary directives.

Using measures such as financial incentives, legislation, and mobile phone applications that provide evidence of food choices, federal policies must shift towards favoring the production and distribution of healthy and good-quality food products.

Governments and the food industry should join efforts to establish policies fostering a healthier food environment for consumers to help fight efficiently against the rising incidence of chronic inflammatory conditions.”