Use of genetically modified lactic acid bacteria and bifidobacteria as live delivery vectors for human and animal health.

There is now strong evidence to support the interest in using lactic acid bacteria (LAB)in particular, strains of lactococci and lactobacilli, as well as bifidobacteria, for the development of new live vectors for human and animal health purposes. LAB are Gram-positive bacteria that have been used for millennia in the production of fermented foods. In addition, numerous studies have shown that genetically modified LAB and bifodobacteria can induce a systemic and mucosal immune response against certain antigens when administered mucosally.

Functional Foods, Nutraceuticals and Probiotics: A Focus on Human Health.

Functional foods are classified as traditional or staple foods that provide an essential nutritional level and share potentially positive effects on host health, including the reduction of disease by optimizing the immune system's ability to prevent and control infections by pathogens, as well as pathologies that cause functional alterations in the host. This chapter reviews the most recent research and advances in this area and discusses some perspectives on what the future holds in this area.

Probiotics and Trained Immunity.

The characteristics of innate immunity have recently been investigated in depth in several research articles, and original findings suggest that innate immunity also has a memory capacity, which has been named "trained immunity". This notion has revolutionized our knowledge of the innate immune response. Thus, stimulation of trained immunity represents a therapeutic alternative that is worth exploring.

Bioactive Compounds in Food as a Current Therapeutic Approach to Maintain a Healthy Intestinal Epithelium.

The intestinal epithelium serves as an effective barrier against the external environment, hampering the passage of potentially harmful substances (such as pathogenic microbes) that could trigger an exacerbated host immune response. The integrity of this barrier is thus essential for the maintenance of proper intestinal homeostasis and efficient protective reactions against chemical and microbial challenges. The principal consequence of intestinal barrier defects is an increase in intestinal permeability, which leads to an increased influx of luminal stressors, such as pathogens, toxins, and allergens, which in turn trigger inflammation and immune response.

Role of Gut Microbiota and Probiotics in Colorectal Cancer: Onset and Progression.

The gut microbiota plays an important role in maintaining homeostasis in the human body, and the disruption of these communities can lead to compromised host health and the onset of disease. Current research on probiotics is quite promising and, in particular, these microorganisms have demonstrated their potential for use as adjuvants for the treatment of colorectal cancer. This review addresses the possible applications of probiotics, postbiotics, synbiotics, and next-generation probiotics in colorectal cancer research.

Probiotic-Based Vaccines May Provide Effective Protection against COVID-19 Acute Respiratory Disease.

Severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) infection, the causative agent of COVID-19, now represents the sixth Public Health Emergency of International Concern (PHEIC)-as declared by the World Health Organization (WHO) since 2009. Considering that SARS-CoV-2 is mainly transmitted via the mucosal route, a therapy administered by this same route may represent a desirable approach to fight SARS-CoV-2 infection. It is now widely accepted that genetically modified microorganisms, including probiotics, represent attractive vehicles for oral or nasal mucosal delivery of therapeutic molecules.

Retraction Note to: Lactobacillus casei BL23 regulates T and Th17 T-cell populations and reduces DMH-associated colorectal cancer.

This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.

Lactobacillus casei BL23 regulates Treg and Th17 T-cell populations and reduces DMH-associated colorectal cancer.

Background: Chronic intestinal inflammation alters host physiology and could lead to colorectal cancer (CRC). We have previously reported beneficial effects of the probiotic strain of Lactobacillus casei BL23 in different murine models of intestinal inflammation. In addition, there is an emerging interest on the potential beneficial effects of probiotics to treat CRC.

Overexpression of Enterococcus faecalis elr operon protects from phagocytosis.

Background: Mechanisms underlying the transition from commensalism to virulence in Enterococcus faecalis are not fully understood. We previously identified the enterococcal leucine-rich protein A (ElrA) as a virulence factor of E. faecalis.

Surface proteome analysis of a natural isolate of Lactococcus lactis reveals the presence of pili able to bind human intestinal epithelial cells.

Surface proteins of Gram-positive bacteria play crucial roles in bacterial adhesion to host tissues. Regarding commensal or probiotic bacteria, adhesion to intestinal mucosa may promote their persistence in the gastro-intestinal tract and their beneficial effects to the host. In this study, seven Lactococcus lactis strains exhibiting variable surface physico-chemical properties were compared for their adhesion to Caco-2 intestinal epithelial cells.

Nuclease A (Gbs0661), an extracellular nuclease of Streptococcus agalactiae, attacks the neutrophil extracellular traps and is needed for full virulence.

Most bacteria of the genus Streptococcus are opportunistic pathogens, and some of them produce extracellular DNases, which may be important for virulence. Genome analyses of Streptococcus agalactiae (GBS) neonate isolate NEM316 revealed the presence of seven genes putatively encoding secreted DNases, although their functions, if any, are unknown. In this study, we observed that respiration growth of GBS led to the extracellular accumulation of a putative nuclease, identified as being encoded by the gbs0661 gene.

Mucosal targeting of therapeutic molecules using genetically modified lactic acid bacteria: an update.

Lactic acid bacteria (LAB) represent a heterogeneous group of microorganisms naturally present in many foods and those have proved to be effective mucosal delivery vectors. Moreover, some specific strains of LAB exert beneficial properties (known as probiotic effect) on both human and animal health. Although probiotic effects are strain-specific traits, it is theoretically possible, using genetic engineering techniques, to design strains that can exert a variety of beneficial properties.

Heterologous production of human papillomavirus type-16 L1 protein by a lactic acid bacterium.

Background: The expression of vaccine antigens in lactic acid bacteria (LAB) is a safe and cost-effective alternative to traditional expression systems. In this study, we investigated i) the expression of Human papillomavirus type 16 (HPV-16) L1 major capsid protein in the model LAB Lactococcus lactis and ii) the ability of the resulting recombinant strain to produce either capsomer-or virus-like particles (VLPs).

Results And Conclusion: HPV-16 L1 gene was cloned into two vectors, pCYT and pSEC, designed for controlled intra- or extracellular heterologous expression in L.

Allergy therapy by intranasal administration with recombinant Lactococcus lactis Producing bovine beta-lactoglobulin.

Background: In the last years, the use of probiotics such as lactic acid bacteria (LAB) has been proposed as an attractive alternative for the management of allergic diseases. A partial prevention from sensitization to bovine beta-lactoglobulin (BLG), one of the major cows' milk allergens, could be achieved in mice after intranasal administration with a recombinant LAB strain, Lactococcus lactis, producing BLG (LL-BLG). This study aimed to evaluate the effects of the LL-BLG strain in a therapeutic protocol.

Production of biologically active CXC chemokines by Lactococcus lactis: evaluation of its potential as a novel mucosal vaccine adjuvant.

Chemokines have been described as essential mediators in leukocytes migration to inflammatory sites and to secondary lymphoid organs. Mig and IP-10 are two CXC chemokines that recruit mononuclear cells in vivo and inhibit angiogenesis. In addition to their chemotactic roles, Mig and IP-10 have also an important role in the adaptative immune response.

Production of biological active murine IFN-gamma by recombinant Lactococcus lactis.

IFN-gamma is a cytokine produced primarily by both T lymphocytes and natural killer cells and it is considered to be an attractive therapeutic molecule. In the present study, a DNA sequence encoding the mature murine IFN-gamma (muIFN-gamma) protein was cloned and expressed in the food-grade lactic acid bacterium Lactococcus lactis. The activity of recombinant muIFN-gamma produced by genetically engineered L.

Current prophylactic and therapeutic uses of a recombinant Lactococcus lactis strain secreting biologically active interleukin-12.

The noninvasive and food-grade Gram-positive bacterium Lactococcus lactis is well adapted to deliver medical proteins to the mucosal immune system. In the last decade, the potential of live recombinant lactococci to deliver such proteins to the mucosal immune system has been investigated. This approach offers several advantages over the traditional systemic injection, such as easy administration and the ability to elicit both systemic and mucosal immune responses.

Influence of the route of immunization and the nature of the bacterial vector on immunogenicity of mucosal vaccines based on lactic acid bacteria.

Mucosal immunity plays a major role in the prevention of infectious diseases. Genetically engineered lactic acid bacteria (LAB) have been tested in the last 10 years as safe mucosal delivery vectors. We previously showed that intranasal co-administration of recombinant lactococci displaying human papillomavirus type 16 (HPV-16) E7 antigen at its surface (LL-E7) and secreting biologically active interleukine-12 (LL-IL-12) has therapeutic effects on HPV-16-induced tumors in mice.

Intranasal coadministration of live lactococci producing interleukin-12 and a major cow's milk allergen inhibits allergic reaction in mice.

The Th1/Th2 balance deregulation toward a Th2 immune response plays a central role in allergy. We previously demonstrated that administration of recombinant Lactococcus lactis strains expressing bovine beta-lactoglobulin (BLG), a major cow's milk allergen, partially prevents mice from sensitization. In the present study, we aimed to improve this preventive effect by coadministration of L.

A novel mucosal vaccine based on live Lactococci expressing E7 antigen and IL-12 induces systemic and mucosal immune responses and protects mice against human papillomavirus type 16-induced tumors.

Current strategies to prevent or treat human papillomavirus type 16 (HPV-16) infection are promising, but remain costly. More economical but efficient vaccines are thus needed. In this study, we evaluated the protective effects of mucosally coadministered live Lactococcus lactis strains expressing cell wall-anchored E7 Ag and a secreted form of IL-12 to treat HPV-16-induced tumors in a murine model.

Cell-surface display of E7 antigen from human papillomavirus type-16 in Lactococcus lactis and in Lactobacillus plantarum using a new cell-wall anchor from lactobacilli.

The human papillomavirus type-16 (HPV-16) E7 protein is considered a major viral oncoprotein involved in cervical cancer (CxCa) and a potential candidate for the development of a vaccine against this neoplasia. Here, two lactic acid bacteria (the model one Lactococcus lactis and a probiotic one Lactobacillus plantarum) were engineered to deliver an E7 mutant protein (E7mm), which has a reduced transforming activity and consequently, could fit better to therapeutic use in humans than the native form of E7. An efficient cell-surface display of E7mm was obtained in L.

An inducible surface presentation system improves cellular immunity against human papillomavirus type 16 E7 antigen in mice after nasal administration with recombinant lactococci.

Human papillomavirus type 16 (HPV-16) is the major causative agent of cervical cancer. To date, vaccine strategies against HPV-16 are based on the ability of the E7 oncoprotein to elicit an immune response against this virus. In this study, the use of an inducible or a constitutive system to produce the HPV-16 E7 protein in Lactococcus lactis, a non-pathogenic and non-invasive Gram-positive bacterium, was compared.

Mice immunization with live lactococci displaying a surface anchored HPV-16 E7 oncoprotein.

E7 oncoprotein of human papillomavirus-16 (HPV-16) is constitutively produced in cervical cancer (CxCa) and is a good candidate for the design of therapeutic vaccines. In this work, the nisin-controlled expression system was used to display the E7 protein at the cell surface of the food-grade Gram-positive bacterium Lactococcus lactis. An efficient cell wall anchoring of E7 was obtained.

Fusion to a carrier protein and a synthetic propeptide enhances E7 HPV-16 production and secretion in Lactococcus lactis.

An inducible system to improve and stabilize the production of an extremely labile protein (E7 antigen of human papillomavirus type 16) was developed in the food-grade bacterium Lactococcus lactis. A protein carrier, the staphylococcal nuclease Nuc, was fused either to N- or C-termini of E7 protein, and the resulting hybrid proteins were rescued from intracellular proteolysis but poorly secreted by L. lactis.