Mycobacterial Hsp65 antigen delivered by invasive Lactococcus lactis reduces intestinal inflammation and fibrosis in TNBS-induced chronic colitis model

Cunha, Vanessa Pecini da; Preisser, Tatiane Melo; Santana, Mariana Passos; Machado, Denise Carmona Cara; Pereira, Vanessa Bastos; Miyoshi, Anderson

doi:10.1038/s41598-020-77276-8

Cited by 7 publications

(4 citation statements)

References 43 publications

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“…Several studies already evidenced the interest in using this strain to deliver in vivo therapeutic proteins in gut inflammation. It was shown that NCDO2118 expressing mycobacterial Hsp65 reduced intestinal inflammation and fibrosis in the TNBS-induced chronic colitis model, a preclinical, experimental model of Crohn's disease (da Cunha et al, 2020). However, only the recombinant strain expressing Hsp65 was tested in vivo, and its benefits, compared with the wild-type strain, have not been assessed.…”

Section: Discussionmentioning

confidence: 99%

Recombinant probiotic Lactococcus lactis delivering P62 mitigates moderate colitis in mice

Laguna,

Freitas,

Barroso

et al. 2024

Front. Microbiol.

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Introduction and objectivep62 is a human multifunctional adaptor protein involved in key cellular processes such as tissue homeostasis, inflammation, and cancer. It acts as a negative regulator of inflammasome complexes. It may thus be considered a good candidate for therapeutic use in inflammatory bowel diseases (IBD), such as colitis. Probiotics, including recombinant probiotic strains producing or delivering therapeutic biomolecules to the host mucosal surfaces, could help prevent and mitigate chronic intestinal inflammation. The objective of the present study was to combine the intrinsic immunomodulatory properties of the probiotic Lactococcus lactis NCDO2118 with its ability to deliver health-promoting molecules to enhance its protective and preventive effects in the context of ulcerative colitis (UC).Material and methodsThis study was realized in vivo in which mice were supplemented with the recombinant strain. The intestinal barrier function was analyzed by monitoring permeability, secretory IgA total levels, mucin expression, and tight junction genes. Its integrity was evaluated by histological analyses. Regarding inflammation, colonic cytokine levels, myeloperoxidase (MPO), and expression of key genes were monitored. The intestinal microbiota composition was investigated using 16S rRNA Gene Sequencing.Results and discussionNo protective effect of L. lactis NCDO2118 pExu:p62 was observed regarding mice clinical parameters compared to the L. lactis NCDO2118 pExu: empty. However, the recombinant strain, expressing p62, increased the goblet cell counts, upregulated Muc2 gene expression in the colon, and downregulated pro-inflammatory cytokines Tnf and Ifng when compared to L. lactis NCDO2118 pExu: empty and inflamed groups. This recombinant strain also decreased colonic MPO activity. No difference in the intestinal microbiota was observed between all treatments. Altogether, our results show that recombinant L. lactis NCDO2118 delivering p62 protein protected the intestinal mucosa and mitigated inflammatory damages caused by dextran sodium sulfate (DSS). We thus suggest that p62 may constitute part of a therapeutic approach targeting inflammation.

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Section: Discussionmentioning

confidence: 99%

Recombinant probiotic Lactococcus lactis delivering P62 mitigates moderate colitis in mice

Laguna,

Freitas,

Barroso

et al. 2024

Front. Microbiol.

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“…Furthermore, the level of the pro‐fibrotic cytokine IL‐13 could be regulated by the gut microbiota. Cunha et al showed that oral administration of Lactococcus lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) reduced the levels of IL‐13 and attenuated the degree of fibrosis in mice with TNBS‐induced colitis 46 …”

Section: Intestinal Fibrosismentioning

confidence: 99%

“…Cunha et al showed that oral administration of Lactococcus lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) reduced the levels of IL-13 and attenuated the degree of fibrosis in mice with TNBS-induced colitis. 46…”

Section: Ligands and Receptors As Anti-fibrotic Targetsmentioning

confidence: 99%

Prospective therapeutics for intestinal and hepatic fibrosis

Zhao

et al. 2023

Bioengineering & Transla Med

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Currently, there are no effective therapies for intestinal and hepatic fibrosis representing a considerable unmet need. Breakthroughs in pathogenesis have accelerated the development of anti‐fibrotic therapeutics in recent years. Particularly, with the development of nanotechnology, the harsh environment of the gastrointestinal tract and inaccessible microenvironment of fibrotic lesions seem to be no longer considered a great barrier to the use of anti‐fibrotic drugs. In this review, we comprehensively summarize recent preclinical and clinical studies on intestinal and hepatic fibrosis. It is found that the targets for preclinical studies on intestinal fibrosis is varied, which could be divided into molecular, cellular, and tissues level, although little clinical trials are ongoing. Liver fibrosis clinical trials have focused on improving metabolic disorders, preventing the activation and proliferation of hepatic stellate cells, promoting the degradation of collagen, and reducing inflammation and cell death. At the preclinical stage, the therapeutic strategies have focused on drug targets and delivery systems. At last, promising remedies to the current challenges are based on multi‐modal synergistic and targeted delivery therapies through mesenchymal stem cells, nanotechnology, and gut‐liver axis providing useful insights into anti‐fibrotic strategies for clinical use.

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“…The gut microbe and related proteins can protect the intestine from fibrotic injury. For example, a study found heat-shock-protein 56 (HSP56) secreted by invasive Lactococcus lactis can reduce the severity of fibrosis (105).…”

Section: Involvement Of the Gut Microbiome In Intestinal Fibrosismentioning

confidence: 99%

Intestinal Fibrosis in Inflammatory Bowel Disease and the Prospects of Mesenchymal Stem Cell Therapy

et al. 2022

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Intestinal fibrosis is an important complication of inflammatory bowel disease (IBD). In the course of the development of fibrosis, certain parts of the intestine become narrowed, significantly destroying the structure and function of the intestine and affecting the quality of life of patients. Chronic inflammation is an important initiating factor of fibrosis. Unfortunately, the existing anti-inflammatory drugs cannot effectively prevent and alleviate fibrosis, and there is no effective anti-fibrotic drug, which makes surgical treatment the mainstream treatment for intestinal fibrosis and stenosis. Mesenchymal stem cells (MSCs) are capable of tissue regeneration and repair through their self-differentiation, secretion of cytokines, and secretion of extracellular vesicles. MSCs have been shown to play an important therapeutic role in the fibrosis of many organs. However, the role of MSC in intestinal fibrosis largely remained unexplored. This review summarizes the mechanism of intestinal fibrosis, including the role of immune cells, TGF-β, and the gut microbiome and metabolites. Available treatment options for fibrosis, particularly, MSCs are also discussed.

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Mycobacterial Hsp65 antigen delivered by invasive Lactococcus lactis reduces intestinal inflammation and fibrosis in TNBS-induced chronic colitis model

Cited by 7 publications

References 43 publications

Recombinant probiotic Lactococcus lactis delivering P62 mitigates moderate colitis in mice

Recombinant probiotic Lactococcus lactis delivering P62 mitigates moderate colitis in mice

Prospective therapeutics for intestinal and hepatic fibrosis

Intestinal Fibrosis in Inflammatory Bowel Disease and the Prospects of Mesenchymal Stem Cell Therapy

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