Helminthic therapy and aging

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Hosting helminths could be key to living longer with greater freedom from chronic disease.

• 2021 Feb 2 Gross ways to live long: Parasitic worms as an anti-inflammaging therapy? -- Full text | PDF (Also reported by EurekAlert. [1])

The following study was the first of its kind to report that weekly administration of the helminth-derived product, ES-62, improved late-life health and increased lifespan (+12%, median lifespan) in a mouse model of high-calorie diet-accelerated aging. This suggests that the anti-inflammatory effects of helminthic therapy can exert protective effects even in later life.

• 2020 Mar 12 The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing -- Full text

Lipopolysaccharide (LPS)

Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as E. coli and Salmonella with a common structural architecture.

Excessive LPS in the blood, endotoxemia, may cause a highly lethal form of sepsis known as endotoxic septic shock. Recent research indicates that even small LPS exposure is associated with autoimmune diseases and allergies. High levels of LPS in the blood can lead to metabolic syndrome, increasing the risk of conditions like diabetes, heart disease and liver problems.

LPS binds Toll like receptor 4 (TLR-4) which is present in various organs and activates an inflammation process.

Helminths can act in 4 different ways:

• reduce the gram-negative bacteria in the microbiota
• fix leaky gut
• maybe send peptides that prevent interaction with the toll-like receptor (TLR) 4/MD2/CD14 complex [2]. (This is yet to be confirmed with therapeutic helminths.)
• the immunomodulatory effect

Relevant papers:

• 2025 Jun 23 Quantitative Proteomics Reveals Fh15 as an Antagonist of TLR4 Downregulating the Activation of NF-κB, Inducible Nitric Oxide, Phagosome Signaling Pathways, and Oxidative Stress of LPS-Stimulated Macrophages (preprint)

• 2025 Mar 3 Nematode serine protease inhibitor SPI-I8 negatively regulates host NF-κB signalling by hijacking MKRN1-mediated polyubiquitination of RACK1 -- Full text | PDF

• 2020 Mar 18 Effects of the dietary fibre inulin and Trichuris suis products on inflammatory responses in lipopolysaccharide-stimulated macrophages (TSO)

• 2017 Nov 28 Human resistin protects against endotoxic shock by blocking LPS-TLR4 interaction

• 2014 Oct The helminth Trichuris suis suppresses TLR4-induced inflammatory responses in human macrophages -- Full txt

• 2013 Jul 11 Cathelicidin-like helminth defence molecules (HDMs): absence of cytotoxic, anti-microbial and anti-protozoan activities imply a specific adaptation to immune modulation -- Full text | PDF

This peptide adopts an amphipathic helix structure and, like LL-37, can bind to Escherichia coli lipopolysaccharide (LPS) to prevent its interaction with the toll-like receptor (TLR) 4/MD2/CD14 complex on macrophages

See also Helminthic therapy and sepsis

The reintroduction to the digestive tract of a controlled number of specially domesticated, mutualistic helminths (intestinal worms) in the form of microscopic eggs or larvae to reconstitute a depleted biome to treat or prevent chronic inflammation, autoimmune disease and other immune-related disorders, including allergy.

An intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. Wikipedia:Helminths

An intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. Wikipedia:Helminths

The reintroduction to the digestive tract of a controlled number of specially domesticated, mutualistic helminths (intestinal worms) in the form of microscopic eggs or larvae to reconstitute a depleted biome to treat or prevent chronic inflammation, autoimmune disease and other immune-related disorders, including allergy.

An intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. Wikipedia:Helminths

The specific population of microorganisms living in a certain part of the body, such as the gut. "Microbiome" refers to all the microorganisms living in and on the body, or the genome of these microorganisms. These two terms are often used interchangeably.

a change which is a result or consequence of an action or other cause.

the ova (eggs) of the porcine (pig) whipworm, Trichuris suis