Undigested Food and Gut Microbiota May Cooperate in the Pathogenesis of Neuroinflammatory Diseases: A Matter of Barriers and a Proposal on the Origin of Organ Specificity

Abstract

As food is an active subject and may have anti-inflammatory or pro-inflammatory effects, dietary habits may modulate the low-grade neuroinflammation associated with chronic neurodegenerative diseases. Food is living matter different from us, but made of our own nature. Therefore, it is at the same time foreign to us (non-self), if not yet digested, and like us (self), after its complete digestion. To avoid the efflux of undigested food from the lumen, the intestinal barrier must remain intact. What and how much we eat shape the composition of gut microbiota. Gut dysbiosis, as a consequence of Western diets, leads to intestinal inflammation and a leaky intestinal barrier. The efflux of undigested food, microbes, endotoxins, as well as immune-competent cells and molecules, causes chronic systemic inflammation. Opening of the blood-brain barrier may trigger microglia and astrocytes and set up neuroinflammation. We suggest that what determines the organ specificity of the autoimmune-inflammatory process may depend on food antigens resembling proteins of the organ being attacked. This applies to the brain and neuroinflammatory diseases, as to other organs and other diseases, including cancer. Understanding the cooperation between microbiota and undigested food in inflammatory diseases may clarify organ specificity, allow the setting up of adequate experimental models of disease and develop targeted dietary interventions.

Keywords: Alzheimer’s disease; Parkinson’s disease; amyotrophic lateral sclerosis; autism spectrum disorders; blood-brain barrier; diet; gut microbiota; inflammation; intestinal barrier; multiple sclerosis.

Figure 1

Chronic neurodegenerative diseases have a chronic inflammatory basis in common.

Figure 2

Dietary habits affect both our metabolism and the composition of our gut microbiota.

Figure 3

Pro-inflammatory dietary factors.

Figure 4

Anti-inflammatory dietary factors. The intrinsic factors are those playing a role in our metabolism. They include: omega-3 poly-unsaturated long-chain fatty acids (n-3 PUFAs), present in fish oil; vitamins A and D, B12, PP, E and C; oligoelements such as magnesium, zinc and selenium; thiolic acids such as alfa-lipoic acid (ALA), N-acetyl cysteine and glutathione. The extrinsic factors are the polyphenols, the phytochemicals present in vegetables: they have anti-inflammatory properties and upregulate the catabolism, but are recognized by our metabolism as “foreign” molecules. However, as shown below, they represent a food source for the gut microbiota. Prebiotics and probiotics are cited here for their anti-inflammatory action, but their effects are exerted mainly through the gut microbiota.

Figure 5

The basic constituents of living matter. The world we know is made up of 92 chemical elements, 81 of which are stable. Living matter uses only about 26–30 of these elements, but 99% of it consists of only four “bioelements”: carbon (C); nitrogen (N); oxygen (O); and hydrogen (H). The bioelements are able to form 4-3-2-1 bonds, respectively, and have a high tendency to get together and form complex molecules such as proteins and nucleic acids, which are different for every species. This means that at the basic level all living organisms are equal to each other, while in their complex forms they are different.

Figure 6

Schematic representation of the metabolic processes, from digestion of the simplest molecules, common to all living organisms and to their fruition.

Figure 7

Effects of dietary factors and stressors on the integrity of the intestinal barrier.

Figure 8

From Westernized dietary habits to neuroinflammation and neurodegenerative diseases: a schematic representation.