Non-Digestible Oligosaccharides and Short Chain Fatty Acids as Therapeutic Targets against Enterotoxin-Producing Bacteria and Their Toxins

Abstract

Enterotoxin-producing bacteria (EPB) have developed multiple mechanisms to disrupt gut homeostasis, and provoke various pathologies. A major part of bacterial cytotoxicity is attributed to the secretion of virulence factors, including enterotoxins. Depending on their structure and mode of action, enterotoxins intrude the intestinal epithelium causing long-term consequences such as hemorrhagic colitis. Multiple non-digestible oligosaccharides (NDOs), and short chain fatty acids (SCFA), as their metabolites produced by the gut microbiota, interact with enteropathogens and their toxins, which may result in the inhibition of the bacterial pathogenicity. NDOs characterized by diverse structural characteristics, block the pathogenicity of EPB either directly, by inhibiting bacterial adherence and growth, or biofilm formation or indirectly, by promoting gut microbiota. Apart from these abilities, NDOs and SCFA can interact with enterotoxins and reduce their cytotoxicity. These anti-virulent effects mostly rely on their ability to mimic the structure of toxin receptors and thus inhibiting toxin adherence to host cells. This review focuses on the strategies of EPB and related enterotoxins to impair host cell immunity, discusses the anti-pathogenic properties of NDOs and SCFA on EPB functions and provides insight into the potential use of NDOs and SCFA as effective agents to fight against enterotoxins.

Antimicrobial Activities of Alginate and Chitosan Oligosaccharides Against Staphylococcus aureus and Group B Streptococcus

“…Non-digestible oligosaccharides (NDOs), complex carbohydrates that resist hydrolysis by salivary and intestinal digestive enzymes and known for their prebiotic properties by stimulating beneficial bacteria in the gut microbiota, These NDOs also exhibit various pathogen reduction capabilities, as reviewed in Asadpoor et al (2020 , 2021a) , and thus may represent potential therapeutic candidates against infections. NDOs, such as human milk oligosaccharides (HMOs), chitosan oligosaccharides (COS), and alginate oligosaccharides (AOS), two NDOs that structurally resemble HMOs, can exhibit anti-biofilm activity ( Ackerman et al, 2018 ; Powell et al, 2018 ; Asadpoor et al, 2021a ), not only by preventing biofilm formation but also by decomposing preformed biofilms probably via the disruption of EPS components ( Powell et al, 2018 ). Furthermore, specific NDOs, and especially HMOs, exert a bacteriostatic effect on bacterial growth ( Craft et al, 2018b ; Asadpoor et al, 2020 ).…”

Dietary Chito-oligosaccharides Improve Intestinal Immunity via Regulating Microbiota and Th17/Treg Balance-Related Immune Signaling in Piglets Challenged by Enterotoxigenic E. coli

“…Chito-oligosaccharides (COSs) are the depolymerization product of chitosan; they have low viscosity and complete water solubility, due to which they can enter the intestine directly and be utilized by the intestinal flora and have a good application effect. − COS has more significant biological properties, such as anti-microbial, anti-oxidation, anti-inflammatory, and anti-hypertensive . COS is also a non-digestible oligosaccharide with various structural features that can mimic toxin receptor structures, bind to toxins of harmful bacteria, and inhibit their adhesion, growth, or biofilm formation, thus blocking the pathogenicity of harmful bacteria directly or indirectly . COS was shown to inhibit the adherence of ETEC to HEp-2 cells by more than 90% .…”

Intestinal Microbiota Contributes to the Improvement of Alcoholic Hepatitis in Mice Treated With Schisandra chinensis Extract

“…SCFA-producing bacteria and lactic acid bacteria (LAB), especially Lactobacillus, Bifidobacterium, and Lachnospiraceae, were enriched in SCE treatment group and altered intestinal SCFAs and lactate levels, which can contribute to the improvement of intestinal functions by SCE. SCFAs, metabolized by gut bacteria from indigestible carbohydrates, help improve the intestinal barrier, protect against enterotoxins, and regulate the microbiome (35). Lactate supports the integrity of the intestinal mucosa, modulates the IM, and can be metabolized to butyrate, propionate, and succinate (36).…”