**8. Novel engineered probiotics/postbiotics/synbiotics**

Novel engineered probiotics based on yeast strains, mainly saccharomyces boulardii, have been constructed to secrete multispecific and single-domain antibodies directly targeting bacterial virulence factors, in particular, enterotoxins [73, 74].

In the last century, the uncontrolled use of antimicrobials has led to a massive increase in *E. coli* resistance representing a threat to public health [75] so the use of an alternative including probiotics and acidifiers was a must [76]. One of the most common substitutes is probiotics *Lactobacillus* spp. and *Bifidobacterium* spp. which are commonly used to combat *E. coli* infections like gastroenteritis [77], antibioticassociated diarrhea [77], necrotizing enterocolitis [78], inflammatory bowel diseases, [79]allergic disorders and others [80].

Furthermore, bioactive molecules secreted by probiotics can effectively downregulate virulence gene expression in enterohemorrhagic *E. coli* O157: H7 [81]. They can also reduce.

*E. coli* O157: H7 and *E. coli* O127: H6 adhesion to epithelial cells monolayers [82, 83]. Unfortunately, probiotics need to be further studied to evaluate their efficacy as anti-biofilm against pathogenic *E. coli*. One of the most common examples of probiotics is Protexin which is a commercially available multistrain potential probiotic [84]. The Protexin contained bacteria that showed antimicrobial activity against *Salmonella Typhimurium* LT2, *E. coli* NCFB 1989, *Staphylococcus aureus* NCTC 8532, *E. faecalis* NCTC 775, and *Clostridium difficile* ATCC 43,594 [85].

Probiotics are capable of controlling MDR bacterial agents by enhancing immune response and competitive exclusion [86]. They augment the activities of macrophages and natural killer cells, modulate cytokine and immunoglobulin secretion, promote intestinal epithelial barrier integrity [87–90] and activate B lymphocytes [89, 91].
