How are the expression patterns of gut antimicrobial peptides modulated by human gastrointestinal diseases? A bridge between infectious, inflammatory, and malignant diseases

Abstract

The human gut barrier is the tissue exposed to the highest load of microorganisms, harbouring 100 trillion bacteria. In addition, the gut's renewal rate outruns that of any other human tissue. Antimicrobial peptides (AMPs) are highly optimized defense molecules in the intestinal barrier optimized to maintain gastrointestinal homeostasis. Alterations in AMPs activity can lead to or result from human gastrointestinal diseases. In this review, unique, conserved, or otherwise regular alterations in the expression patterns of human AMPs across gastrointestinal inflammatory and infectious diseases were analyzed for pattern elucidation. Human gastrointestinal diseases are associated with alterations in gut AMPs' expression patterns in a peptide-specific, disease-specific, and pathogen-specific way, modulating human gastrointestinal functioning. Across diseases, there is a (i) marked reduction in otherwise constitutively expressed AMPs, leading to increased disease susceptibility, and a (ii) significant increase in the expression of inducible AMPs, leading to tissue damage and disease severity. Infections and inflammatory conditions are associated with altered gene expression in the gut, whose patterns may favour cellular metaplasia, mucosal dysfunction, and disease states. Altered expression of AMPs can thus thrive disease severity and evolution since its early stages. Nevertheless, the modulation of AMP expression patterns unveils promising therapeutic targets.

Probiotics and Amelioration of Rheumatoid Arthritis: Significant Roles of Lactobacillus casei and Lactobacillus acidophilus

“…The gastrointestinal tract is connected with the environment, and it is an essential getaway for the intake of beneficial and harmful microbes and their metabolites through food and drinks. The human gut harbors over 100 trillion bacteria, and these microbes have a potential role in the digestion, metabolism, nutrition, disease control, and maintenance of general well-being [ 55 , 56 , 57 , 58 ]. The epithelial cell barrier and intestinal single cell layer determine the rate of entry of microbes or antigens into the bloodstream [ 59 , 60 ].…”

Antimicrobial peptides – Advances in development of therapeutic applications

“…This Gram-negative bacterium specifically hijacks immune responses including evading the host defense shield and selectively compromising AMPs production to allow colonization [ [84] , [85] , [86] , [87] ]. Moreover, H. pylori can also promote (hepatic) malignancy both inside and outside of the gastrointestinal (GI) tract, even if it translocates across the intestinal barrier or not [ 88 ].…”

Targeting Probiotics in Rheumatoid Arthritis

“…Spore organisms can be found in abundance in soil. As individuals eat spores from everyday interactions with soils, they germinate in our small intestine and can survive there for up to three weeks [ 80 ]. These subsequently revert to spores and are discharged into the atmosphere until they are picked up by another host.…”

“…Randomized controlled clinical trials (RCTs) and meta-analyses on infectious illnesses, bacterial diarrhea, inflammatory bowel diseases, abdominal discomfort and colitis have widely identified and supported their health effects [ 80 ]. Even though just a few RCTs had researched the impact of probiotics in RA patients, the results have been promising [ 81 ].…”