Lyme disease can cause a disruption to collagen. This can lead to many symptoms. Optimize Lyme disease treatments: support your collagen and connective tissue.
Lyme disease and associated co-infections have become a pervasive epidemic. More than 300,000 cases of Lyme disease are diagnosed annually in the US, and these numbers are likely significantly under-reporting the incidence of infection. Simultaneously, the chronic disease patient population experiences many complex symptoms related to a loss of extracellular matrix (ECM) function, and associated connective tissues. Review of the literature reveals that stealth pathogens such as Borrelia and Bartonella disrupt the connective tissue in a number of significant ways. Understanding these mechanisms can lead to the development of new therapies aimed at supporting ECM and connective tissue functions.
The Extracellular Matrix (ECM)
The extracellular matrix (ECM) is an important component of physiology. The ECM is comprised of connective tissue, collagen, proteoglycans, glycosaminoglycans, matrix-charged water, and the amorphous gel-like space known as the interstitium. Some of the important functions of the ECM include:
- Providing the structural framework and scaffolding for cells (4)
- Regulation of cell-to-cell communication (2)
- Regulation of the life cycle of cells (3)
- Modulating the balance between cell survival and apoptosis (cell-programmed death) (1)
- Critical regulation of stem cells, growth factors and cytokine signaling (5, 6, 7)
Hence, the critical functions of the ECM are integral to the behavior and function of our cells, our immune system, nervous system, and our endocrine system.
Joint hypermobility syndromes are a significantly under-diagnosed spectrum of conditions that reflect a loss of connective tissue and extracellular matrix functions. There are essentially 2 types of joint hypermobility: those with a congenital/genetic cause and those with a non-genetic cause. The non-genetic type appears to be brought about as the result of some chronic illness, which may involve stealth infections.
A loss of extracellular matrix function and associated joint hypermobility can lead to a number of symptoms. Some of these include:
- MCAS (mast cell activation syndrome)
- Pain syndromes
- Neuropathies & neurological-related conditions
- Anxiety disorders and psychiatric manifestations
- Rheumatic conditions
- Autoimmune conditions such as: SLE (systemic lupus erythematosus), RA (rheumatoid arthritis), MS (multiple sclerosis), Crohn’s disease, Celiac disease, TRAPS, among others
Lyme Disease & Co-infections: Invasion of the ECM
One of the most striking examples of how Lyme disease co-infections can wreak havoc on the extracellular matrix and connective tissues comes from a 2018 study that looked at the effects of Bartonella infection, rheumatological symptoms and associated joint hypermobility (8). The case study publication concerned a female veterinarian who displayed the clinical symptoms of EDS (Ehlers-Danlos Syndrome), Type 3. Type 3 EDS is considered to be the most severe form of EDS, chiefly affecting the vascular system, and leading to a significantly reduced life expectancy. The patient was identified as having a Beighton hypermobility score of 7/9.
The patient was found to have Bartonella koehlerae and Bartonella henselae infections. Bartonella bacterial infections have a notable and destructive effect on the vasculature and endothelial functions. The patient was treated for bartonella using the longterm use of antibiotics. The treatment resulted in the resolution of the patient’s symptoms, and notably the Beighton hypermobility score was recorded post treatment as 0/9, a dramatic shift from a 7/9 score pre-treatment. These findings reveal the vast implications stealth infections (and the tissue-inflammation they invoke) have on the connective tissue.
Bartonella is an intracellular bacterial infection. In order to arrive at it’s target locations, bartonella stealthily works its way through the ECM and connective tissue through a series of mechanisms. It is known that Bartonella directly interacts with the connective tissue:
- Bartonella binds collagen types 9 and 10 (9)
- Bartonella adhesins bind ECM integrins (9)
- Bartonella is believed to bind collagen type 4, vitronectin, laminin and hyaluronic acid (9)
- Bartonella binds heparin and fibronectin (10)
Borrelia: Lyme Disease & Connective Tissue
Borrelia burgdorferi is the main bacterial pathogen causative in Lyme disease, however other forms of Borrelia have been identified. One of Borrelia’s primary targets is in fact the host’s extracellular matrix and collagen system (11). Borrelia’s target in the ECM can prevent detection by host immune cells. Borrelia uses its adhesins to bind itself to the host’s glycosaminoglycans and proteoglycans in the connective tissue (13). Lyme disease bacteria can cause a degradation of the collagen and extracellular matrix.
- Borrelia highjacks the host’s plasminogen, leading to subsequent activation of host plasmin, which acts to degrade collagen through collagenase synthesis (11)
- Activation of inflammatory metalloproteinases (12)
Sudden Onset Joint Hypermobility: Possible Indication of Lyme Disease & Stealth Infections
Many patients report experiencing joint hypermobility or skin hyperelasticity following the onset of some chronic illness or subset of symptoms. This strongly suggests an inflammatory process occurring in the connective tissue. Additional symptoms which may implicate Lyme or stealth co-infections affecting the connective tissue may include:
- MCAS (mast cell activation syndrome)
- POTS (postural orthostatic tachycardia)
- Raynaud’s or discoloration of fingers or toes
- Sagging skin with lack of tissue integrity
- Chronic headaches
- Migrating joint pain
- Burning, tingling sensations
- Crawling sensations under skin
- Sensitivity to touch, sound or smell
- Seizures or involuntary jerking movements
One potential mechanism of how hypermobility could form as a result of Lyme disease or it’s co-infections is through cell danger signaling induced through connective tissue Fibroblast cells.
Fibroblast cells are the main cell type that produce the constituents of the extracellular matrix and collagen networks. It is known that these types of cells exist in a cross talk with neighboring mast cells (14). The cell danger response (CDR), a term developed by Dr. Robert Naviaux highlights the distinct role of mitochondria-coordinated danger signaling through purinergic receptors and extracellular nucleotides. Purinergic signaling is one of the key cellular, coordinated mechanisms that alters cellular metabolic function and behavior during perceived threats of cellular danger (17).
These purinergic receptors do in fact exist on the surface of fibroblast cells, and are known to be involved in coordinated danger signaling and inflammatory activities (15, 16). For example, purinergic signaling is strongly involved with fibroblast cells during tissue fibrosis (15). How purinergic signaling is involved in sudden onset joint hypermobility has not yet been studied.
What Can Be Done To Support Collagen Production During or After Inflammation?
If Lyme disease, Bartonella, Babesia, toxic metals, or mold exposure is associated with causing sudden onset joint hypermobility, then these issues should be addressed as a primary concern. It may very well be the case that some individuals are predisposed towards weaker connective tissue, due to genetic variations in collagen genes such as the COL family or the Tenascins. In these cases, the epigenetic vector is the proverbial straw that breaks the camel’s back.
Nutritional Support For Connective Tissue & Collagen
Polysaccharides derived from: Aloe vera, marine brown and red algae or mushrooms such as maitake and Lion’s mane may be greatly beneficial to support collagen synthesis. There is a significant body of clinical evidence that polysaccharides from various supplements can improve, or even correct collagen-deficiency symptoms such as subluxation, dislocation, popping joints, organ prolapse and hyperextensible joints.
The following supplements may be useful to support collagen:
- Fucoidans derived from algaes have shown to inhibit pro-inflammatory and ECM-degrading metalloproteinases, as well as to inhibit the enzymes which degrade hyaluronic acid (18)
- Acemannan derived from aloe vera has shown in rats to increase collagen 1, fibroblast proliferation as well as growth factors in the repair of oral injury (19)
- Vitamin C – Ascorbate notably increases collagen synthesis through increasing enzymes lysyl hydroxylase and prolyl hydroxylase (20)
- Copper – is an important cofactor in the collagen-synthesizing enzyme lysyl oxidase. Different forms of copper may be useful. A copper peptide known as GHK Copper may effectively promote collagen turnover, wound healing, glycosaminoglycan synthesis and blood vessel formation (21)
- Amino acids: Proline & Glycine together with hydroxyproline form the triple helical structure of collagen
- IgF-1 is an important growth factor and activator of growth hormone. Importantly, Igf-1 increases types 1 and 3 collagen, as well as promotes the function of enzymes lysyl oxidase and lysyl hydroxylase (23). A non-peptide molecule known as Ibutamoren aka MK677 is a potent promoter of IgF-1 as well as growth hormone (24). This molecule holds potential value for a number of conditions, and is currently undergoing clinical trials.