The lymphoid follicles and toll-like receptor (TLR) expression

The healthy human gut is colonized by roughly 1014 resident microbes. Among them bacteria, viruses, fungi, and protozoa are most common. They have symbiotic relationship with the human intestinal tract. These microbes maintain ecosystem of incomparable diversity, termed as microbiota 1. Major bacterial groups in the microbiota are gram positive Firmicutes and gram negative Bacteroidetes 2, 3. Vast number of microbes live within the distal parts of the gut, around 1011 cells per gram content 4. Microorganisms in the large intestine biosynthesize vitamins and essential amino acids, as well as metabolic byproducts from food left undigested by the small intestine which contribute to host health 5. Byproducts of short chain fatty acid (SCFA) e.g. butyrate, propionate, and acetate are the major energy source for intestinal epithelial cells and may therefore strengthen the mucosal barrier 6. Several studies conducted using germ-free mice which suggest that the commensal microbiota act on antigen presenting cells, differentiated T cells, lymphoid follicles and toll-like receptor (TLR) expression and promote local intestinal immunity 7, 8,9. They also induce systemic immunity through increased splenic CD4+ T cells and systemic antibody expression 10.

Healthy gut microbiota can prevent colonization of enteric pathogens, called colonization-resistance (CR). When gut microbial composition altered, it creates disruption in CR, and pathogens can gain the opportunity to grow to high levels. This disruption can be caused by application of probiotics and drugs, exposure to antibiotics, changes in diet and a variety of diseases. Altered microbiota composition is linked with number of human disease conditions, such as autoimmune and immune mediated phenomena -inflammatory bowel diseases (IBD), type 2 diabetes, obesity, allergies and colorectal cancer (11). Changes in food habit -for example complete shift to animal-based to plant-based or vice versa alters microbial composition within just 24 h which could be reversed within 48 h of diet discontinuation 12. Additionally, the gut microbiota of animals fed a high-fat or high-sugar diet is more prone to circadian rhythm disruption 13. Systemic stress and inflammation can also cause acute changes in the intestinal microbiota within just one day of the sustained stress 14.

Autoimmune disease, a major medical concern in the world since the disease mechanisms responsible for its induction and development are poorly understood. In normal physiological conditions, the immune system shows tolerance to molecules recognized as ”self,”. For this reason, does not respond to carbohydrate, protein and nucleic acid that are expressed in endogenous tissues. When self-tolerance is lost, the immune system is deployed against one or more of the body’s own molecules which is hallmark of the autoimmune diseases (AIDx). The primary cause of any AIDx is a reduced capacity for self-tolerance due to a failure in ”central” processes (i.e., in primary lymphoid organs) and/or ”peripheral” means (i.e., secondary lymphoid organs and/or inflamed tissues) for removing or repressing autoreactive immune cell lineages. 15