Lipopolysaccharides: Strategies for Treating Endotoxin-Induced Health Issues

Lipopolysaccharides (LPS), or endotoxins, are components of the outer membrane of Gram-negative bacteria that can provoke significant immune responses when they enter the human body, leading to various health issues.

This article discusses the health impacts of LPS exposure and strategies for treating conditions caused by endotoxin exposure, encompassing both medical and lifestyle interventions.

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What Are Lipopolysaccharides (LPS)?

Lipopolysaccharides (LPS) are components of the outer cell membrane of gram-negative bacteria. The gram-negative bacterial cell membrane consists of an inner and outer membrane. LPS molecules are considered bacterial toxins. When they enter the body during an infection they can trigger a severe immune reaction.

LPS are composed of three main parts, Lipid A, which is the most virulent factor, O-antigen, and a hydrophilic core. The O-antigen varies between different bacterial strains and provides antigenic specificity aiding in the diagnosis of active infection.

How Do Lipopolysaccharides (LPS) Contribute to Diseases?

LPS enters the blood through a bacterial infection and leads to a series of immune reactions.

Secretion of several pro-inflammatory cytokines through activation of toll-like receptors (TLRs).
After the TLRs recognize the LPS it causes the release of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-a), IL-6, and IL-8.
Once the cytokines are released into the bloodstream, they cause widespread inflammation and activation of reactive oxygen species (ROS), which produces an overwhelming immune response and oxidative stress in the body.
The severity of the immune response can lead to cell damage with potentially lethal effects.

The following are common health issues associated with high levels of endotoxin exposure:

Sepsis
Neurodegenerative diseases such as ALS, Parkinson’s, and Alzheimer's
Metabolic disease
Cardiovascular diseases such as atherosclerosis and vascular inflammation
Coagulopathy increases the risk of stroke
Irritable bowel disease
Chronic pain and chronic fatigue
Chronic Inflammatory Response Syndrome (CIRS)

How to Treat Endotoxin-Induced Conditions

The medical approach to treating endotoxin illness primarily focuses on using targeted antibiotics to eradicate the underlying bacterial infection alongside supportive therapies to manage inflammation and prevent complications.

The Medical Approach to Treating Endotoxin-Induced Conditions

Antibiotics:

Gram-negative bacteria that contain LPS are some of the hardest infections to treat due to antibiotic resistance. Conventional antibiotic therapy for gram-negative bacteria effectively kills the bacteria but does not effectively neutralize LPS.

Among antibiotics currently being used for endotoxin-induced conditions are beta-lactam antibiotics such as carbapenems, which have shown a reduced risk of sepsis. For less severe infections caused by gram-negative bacteria, the use of fluoroquinolones and aminoglycoside antibiotics has shown efficacy if started promptly.

Endotoxin Neutralization:

An alternative strategy to managing endotoxin-related illness is through neutralizing the LPS. This can be accomplished with Polymyxin B, an antibiotic that can kill gram-negative bacteria and bind circulating endotoxin without causing systemic toxicity.

Polymixin drugs target the bacterial cell membrane causing bacterial lethality, however, they can cause nephrotoxicity and neurotoxicity. For this reason, polymyxin use is limited and only reserved as a last-line treatment for endotoxin-related illness.

Anti-inflammatory Medications:

Endotexmia can cause widespread inflammation in the body causing serious complications. While antibiotics are necessary for treatment, incorporating medications to reduce inflammation is crucial.

Anti-inflammatory medications such as NSAIDs and corticosteroids can help diminish the inflammation caused by endotoxin illness.
Low-dose hydrocortisone is effective in reducing cytokine production and systemic inflammation caused by endotoxemia (2).

The Complementary Approach to Support Treatments of Endotoxin-Induced Conditions

Probiotics and Gut Health:

Endotexmia develops when endotoxins such as LPS reach the bloodstream due to increased intestinal permeability. Intestinal permeability can allow harmful microorganisms and toxins to enter the bloodstream. Maintaining a healthy microbiome and implementing probiotics can help strengthen the gut wall, reducing endotoxin production and the chance of endotoxins reaching the bloodstream.

Spore-based probiotics such as Bacillus indicus, Bacillus subtilis, and Bacillus coagulans reduce symptoms of leaky gut syndrome. These spore-based probiotics are associated with a 45% reduction in endotoxin levels in the blood. Lactobacillus probiotics are also effective in maintaining a healthy gut wall by enhancing goblet cells, a mechanism used to enhance barrier function (1).

Implementing nutraceuticals such as L-glutamine helps regulate tight junctions in the gut which reduces intestinal permeability and reduces intestinal endotoxin levels. Polyphenols such as quercetin, curcumin, and resveratrol also enhance tight junction integrity, improving intestinal permeability.

Dietary Modifications:

Making dietary changes to reduce processed foods and incorporating anti-inflammatory foods can help heal leaky gut and aid in preventing and treating endotoxin-related illnesses. The following are dietary recommendations to reduce inflammation and heal leaky gut:

Decrease intake of processed carbohydrates such as sweetened beverages, bread, snack foods, and alcohol, as these foods are associated with a decreased microbiome diversity
Incorporate foods high in fiber, such as fruit and vegetables
Including coffee, tea, and red wine in moderation helps increase beneficial bifidobacteria in the gut
Decrease intake of fermentable oligosaccharides (FODMAPs) such as fructans, sorbitol, and xylitol as they lead to intestinal inflammation and a weakened gut wall.
Increasing intake of yogurt can help protect the intestinal epithelium
Medicinal mushrooms such as Chaga can modulate gut microbiota and decrease intestinal inflammation

Hydration and Detoxification:

Incorporating detoxification strategies can assist in flushing out bacterial toxins from the body.

Focus on activities that make you sweat, such as physical exercise and sauna use, to help decrease total toxin load (5)
Increasing hydration helps support the kidneys in filtering out bacterial toxins and waste products from the blood
Supporting liver detox with berberine, milk thistle, and glutathione (41)
Castor oil packs over the liver decrease inflammation and support detoxification

Innovative Research and Emerging Treatments

Toll-like receptor 4 (TLR4) is the main signaling pathway in endotoxin-related illness. Modulation of the TLR4 pathway through natural and synthetic sources is an emerging strategy to reduce bacterial endotoxin disease.

Berberine blocks the TLR4 pathway and reduces NF-Kb signaling, leading to decreased systemic inflammation.
Humulus lupulus (Hops) has shown anti-inflammatory effects by blocking TLR4 activation
Sulforaphane, naturally found in cruciferous vegetables, blocks LPS interaction with TLR4 receptors
Synthetic compounds such as resatorvid and eritoran block TLR4 activity by mimicking the lipid A portion of LPS

Gene Therapy and Molecular Techniques

Gene therapy and molecular techniques for endotoxin-related illnesses are an emerging area of research that aims to address the underlying mechanisms of immune response and inflammation triggered by LPS. Anti-microbial peptides (AMPs) such as cathelicidin, have shown promising efficacy in the neutralization of gram-negative bacteria (42).