Role of immunomodulatory probiotics in alleviating bacterial diarrhea in piglets: a systematic review

Abstract

Diarrhea is a common enteric disease in piglets that leads to high mortality and economic losses in swine production worldwide. Antibiotics are commonly used to prevent or treat diarrhea in piglets. However, irrational antibiotic use contributes to the development of resistance in bacteria and antibiotic residues in animal products, threatening public health, while causing gut microbiota dysbiosis and antibiotic-resistant bacterial infection in piglets. Therefore, the quest for alternative products (such as probiotics, prebiotics, organic acids, enzymes, essential oils, medium-chain fatty acids, zinc, and plant extracts) has recently been clearly emphasized through the increase in regulations regarding antibiotic use in livestock production. These antibiotic alternatives could lower the risk of antibiotic-resistant bacteria and meet consumer demand for antibiotic-free food. Several antibiotic alternatives have been proposed, including immunomodulatory probiotics, as candidates to reduce the need for antimicrobial therapy. Many studies have revealed that probiotics can avert and cure bacterial diarrhea by regulating the gut function and immune system of piglets. In this review, we focus on the major pathogenic bacteria causing piglet diarrhea, the research status of using probiotics to prevent and treat diarrhea, their possible mechanisms, and the safety issues related to the use of probiotics. Supplementation with probiotics is a possible alternative to antibiotics for the prevention or treatment of bacterial diarrhea in piglets. Furthermore, probiotics exert beneficial effects on feed efficiency and growth performance of piglets. Therefore, appropriate selection and strategies for the use of probiotics may have a positive effect on growth performance and also reduce diarrhea in piglets. This review provides useful information on probiotics for researchers, pig nutritionists, and the additive industry to support their use against bacterial diarrhea in piglets.

Keywords: Clostridium; E. coli; Diarrhea; Immunomodulatory effect; Piglets; Probiotics.

Fig. 1

Diagram flow of manuscripts selection for this review

Fig. 2

Visualization of A) E. coli (Enterotoxigenic, ETEC with fimbriae and enterotoxins), B) E. coli (Enteropathogenic, EPEC with intimin), C) Salmonella spp. with their effectors, and D) Clostridium spp. with enterotoxins. Abbreviations: F4, F5, F6, F18, F41, Fimbriae; LT, heat liable toxin; ST, heat stable toxin, EAST, Enteroaggregative heat stable toxin; T3ss, Three secretion systems; CPA, Clostridium perfringens toxin alpha; CPB, Clostridium perfringens toxin beta; ETX, Clostridium perfringens toxin epsilon; ITX, Clostridium perfringens toxin iota; TedA, Clostridium difficile toxin A, TedB, Clostridium difficile toxin B (Created with BioRender.com)

Fig. 3

Interaction of probiotics on the intestinal barrier and its application in treating in piglets diarrhea. Probiotics alleviate diarrhea by regulating the intestinal microbial and mucosal barrier: 1) competitive exclusion of pathogen, 2) producing antimicrobial substance and neutralize toxins, 3) restore beneficial microbes, 4) upregulation of intestinal tight junction protein expression, 5) stimulate the secretion of mucin and peptides, and 6) reduce pH in intestine and helps to maintain normal intestinal permeability. Abbreviations: SCFAs, Short chain fatty acids (Created with BioRender.com)

Fig. 4

Probiotic modulation of gut associated immune system through TLR pathway regulation. Both pathogenic (red) bacteria (ETEC/Salmonella/Clostridium) and probiotic (green) bacteria can express similar/overlapping profiles of PAMPs/MAMPs (LTA, LPS, Flagellin) through a range of PRRs including TLR2, TLR4, TLR5. All of which can transduce immune activatory/inflammatory responses through activation of NFkB and MAPK signal pathways (indicated in black arrows). Probiotic-derived MAMPs (indicated as green), induce a suppressive/tolerogenic response via the induction of endogenous negative regulators to TLR signals (Tollip, IRAK-M, Myd88s, A20, Bcl3 and MKP-1) that inhibit NFkB and MAPK pathways. Abbreviations: LPS, Lipopolysaccharide; PAMPs, Pathogen-associated molecular patterns; MAMPs, Microbial associated molecular patterns; TLR2, Toll like receptor 2; TLR4, Toll like receptor 4; TLR5, Toll like receptor 5; TIRAP, Toll-interleukin-1 Receptor domain containing adaptor protein; TRAM, Translocating chain associating membrane protein; MyD88, Myeloid differentiation primary response gene 88; IRAK-M, Interleukin-1 receptor associated kinase M; TRAF6, Tumor necrosis factor associated factor 6; MAPK, Mitogen activated protein kinase; IκBα, IkappaB alpha; JNK, c-JUN N-terminal kinase; ERK, Extracellular signal-regulated kinase; p38, 38 kDa protein; NF-κB, Nuclear factor kappa B; A20, Tumor necrosis factor-α-inducible protein 3; Bcl3, B-cell lymphoma 3-encoded protein; MKP-1, Mitogen-activated protein kinase phosphatase-1 (Created with BioRender.com)