Join Here   |   Log In

Chronic Lyme: Genetic Susceptibility

Key takeaways:
~ Lyme disease is caused by bacteria in tick bites.
~ For some, the illness is limited and resolves easily, but for others, chronic and debilitating symptoms can last for years.
~ Genetic variants are part of why Lyme disease affects people differently. Genes also play a role in how well antibiotics work to cure Lyme.

Members will see their genotype report below, plus additional solutions in the Lifehacks section. Consider joining today 

Background on Lyme Disease:

Lyme disease affects ~476,000 people a year in the US. While initially only in the Northeast and upper Midwest, ticks carrying Lyme disease are now found in almost all states.[ref][ref]

In North America, Lyme disease is caused by Borrelia burgdorferi, a bacteria carried by black-legged (deer) ticks.

Symptoms of Lyme include:

  • fever
  • headache
  • fatigue
  • bulls-eye rash (erythema migrans) – sometimes

The CDC’s data on Lyme disease dates back to 1991, but reports of Lyme disease go back to the mid-1970s. The number of cases has grown steadily since the early ’90s, and the areas where the disease is found have spread across the country.[ref]

In Europe, Lyme is also present and sometimes called Borreliosis. Cases can involve genospecies of Borrelia, including B. afzeliiB. garinii, and B. valaisiana.[ref][ref]

The Borrelia species are a type of bacteria known as a spirochete. Our immune system has difficulty recognizing this bacterial spirochete because the surface proteins continually change, which keeps the pathogen one step ahead of the acquired immune response.[ref]

An excellent overview of the history of Lyme disease can be found in PMC7946767.

Can Lyme disease be completely cured?

Several weeks of antibiotic treatment will cure Lyme disease for most people.[ref]

Unfortunately, not everyone reacts the same way to Lyme disease.

Genetic variants can cause some people’s immune systems to act differently towards the Borrelia species, and other genetic variants can influence how well antibiotics work within your cells.

Screenshot from PMC8046170, another great overview of Lyme.

What is chronic Lyme disease?

People use the term chronic Lyme to indicate they still have symptoms such as fatigue and brain fog after undergoing antibiotic treatment for Lyme disease.

Symptoms can sometimes last for years, significantly impacting quality of life. Chronic Lyme can be hard to diagnose, with some sufferers seeing multiple physicians and going years without a definitive diagnosis.

Controversy: There seems to be a lot of swirling controversy regarding the diagnosis of chronic Lyme because it was initially dismissed by some physicians who called it psychosomatic. Even recent articles, such as this one, use terminology such as “supposed symptoms” and claim that the “medical establishment maintains that there is no such thing as chronic Lyme”.

The term chronic Lyme is also often applied to people who don’t feel well (fatigue, brain fog) but also haven’t ever had blood tests that show up positive for Borrelia burgdorferi. The vague usage and alternative medical diagnoses have caused a big backlash from mainstream medical people. Chronic Lyme as a polarizing topic leaves patients getting the short end of the stick.

Encouragingly, research is now catching up on chronic Lyme symptoms and treatments.

Researchers and doctors now use the term Post Treatment Lyme Disease (PTLD). There are now hundreds of solid studies on PTLD syndrome showing the physiological and cellular changes in people with PTLD.

What is Post Treatment Lyme Disease Syndrome (PTLD)?

PTLD syndrome is much easier to define than chronic Lyme. After receiving standard treatment for Lyme (several weeks of antibiotics), some people continue to have ‘clinically relevant’ pain, fatigue, sleep disturbance, depression, and lower quality of life. Often, blood tests for these patients are normal. This has been well documented in several studies.[ref]

PTLD with significant symptoms affects between 10 and 20% of people treated for Lyme, according to official estimates. Other studies show that mild symptoms, whether ‘clinically relevant’ or not, remain for half or more of patients after treatment.[ref][ref]

Symptoms used in research studies to identify PTLD include:[ref]

  • muscle pain
  • joint pain
  • fatigue
  • memory problems
  • difficulties concentrating and problems finding words
  • impact on daily activities

While these symptoms can also be due to other underlying causes, a recent study found that people with a history of Lyme disease were five times more likely to meet the criteria for PTLD than those with no prior Lyme diagnosis.[ref]

The results of a recent study showed that the long-term cognitive problems in PTLD continued without improvement for 12+ months after completing treatment. More encouragingly, the fatigue scores did improve a little over the course of a year.[ref]

What causes PTLD?

There are several possibilities.

  1. Bacteria (B.burgdorferi) that remain in the body, even after aggressive antibiotics.[ref]
  2. The inability of some antibiotics to kill Borrelia burgdorferi in biofilm-like structures.[ref]
  3. Inflammatory Borrelia burgdorferi components remain after the bacteria are killed.[ref]

The question then becomes: Why do 10 -20% of people treated for Lyme not recover completely?

With over 400,000 Lyme cases per year just in the US, that could leave 60,000 people per year who deal with chronic, long-lasting symptoms.

One study estimates that by 2020 the cumulative number of people dealing with PTLD could be as high as 1.9 million.[ref]

Lower initial immune response?
Research shows that patients with the bull’s-eye rash (erythema migrans) were 3-times less likely to end up with chronic Lyme when compared to patients with disseminated Lyme (later symptoms).[ref] Perhaps a stronger initial immune reaction determines who gets PTLD?

A recent study showed that non-viable components of B. burgdorferi stimulated a higher immune response in brain cells than the total bacteria.[ref] Components of the bacteria wouldn’t be affected by antibiotics, which may explain why taking more rounds of antibiotics doesn’t knock out the infection.

What is different in people with persistent Lyme?

Genetics can play a role in how well treatments for Lyme disease work and help us understand what is happening.

A 2019 study found that genetically based hyperinflammation may play a role. The chronic Lyme patients had imbalanced IL-6 along with elevated IL-1β and IL-8 (inflammatory cytokines).[ref]

Proteomics studies look at the differences in the blood proteins of people with chronic Lyme compared with people who had Lyme and recovered and those who never had Lyme. The research shows a clear difference in the blood proteins in people with PTLD.

A new study found that 35 biomarkers could be used to identify chronic Lyme. Several immune system pathways are involved. Interestingly, a couple of the genes are also related to epilepsy (CACNB4, ALDH7A1, SCN3A) which could be a molecular reason for the neurological symptoms of PTLD.[ref]

Chronic Lyme Genotype Report:

Members: Log in to see your data below.
Not a member? Join here.
Why is this section is now only for members? Here’s why…

Member Content:

An active subscription is required to access this content.

Join Here

Already a member? Log in below.


If you find a tick and have symptoms of Lyme, the earlier you get treated, the better the odds are of a complete recovery.[ref][ref]

There are several ongoing clinical trials for different protocols to determine the best treatments for Lyme, so hopefully, more answers will be available soon.[ref]

Medication options:

Regarding chronic Lyme, research shows that more antibiotics after the initial course aren’t likely to help.[ref][ref]

Pulse dosing with ceftriaxone after other antibiotics doesn’t seem to work very well either.[ref]

A randomized controlled trial found that amoxicillin (20-day course) was a little more effective than azithromycin (7-day course).[ref] If you have a choice of antibiotics and no allergies to either, amoxicillin might be your better option — but this is definitely one of those things to talk about with your doctor.


In a trial of steroids along with antibiotics for Lyme disease associated with facial palsy, the results showed worse outcomes for patients with steroids.[ref]


The anti-alcohol abuse drug disulfiram was identified as a highly active compound against Borrelia. Three case studies of people with PTLD treated with disulfiram showed positive results. Disulfiram also is a drug candidate for treating parasites and viruses.[ref]

The case studies are open access, so you may want to read them and talk with your doctor (especially about the side effects, which include psychiatric disturbances).[ref]

Research studies on natural treatments for chronic Lyme:

There are a lot of websites that sell natural cures for chronic Lyme disease, but it can be hard to tell if they really work or not. I’ll just cover the research-backed options here.

Research on essential oil blend:

Member Content:

An active subscription is required to access this content.

Join Here

Already a member? Log in below.

Related Articles and Topics:

COMT – A gene that affects your neurotransmitter levels
Having trouble with supplements containing methyl groups? Wondering why your neurotransmitters are out of balance? It could be due to your COMT genetic variants. This important enzyme is tasked with breaking down neurotransmitters, such as dopamine.

Nickel Allergy: Genetics, causes, natural solutions
Nickel allergy can cause sensitivity to foods that contain nickel. Learn about how genes increase susceptibility and solutions.

Brain Fog: Causes, genetics, and individualized solutions
Explore brain fog in detail, looking at the physiological causes, genetic susceptibility, and personalized solutions.

Inflammation: Causes and Natural Solutions
Take a deep dive into the causes of chronic inflammation and learn how to target specific inflammatory pathways to reverse or prevent chronic disease.



Andreassen, Silje, et al. “Cognitive Function in Patients with Neuroborreliosis: A Prospective Cohort Study from the Acute Phase to 12 Months Post Treatment.” Brain and Behavior, vol. 12, no. 6, June 2022, p. e2608. PubMed,

Aucott, John N., et al. “Risk of Post-Treatment Lyme Disease in Patients with Ideally-Treated Early Lyme Disease: A Prospective Cohort Study.” International Journal of Infectious Diseases: IJID: Official Publication of the International Society for Infectious Diseases, vol. 116, Mar. 2022, pp. 230–37. PubMed,

Berende, Anneleen, Hadewych J. M. Ter Hofstede, et al. “Effect of Prolonged Antibiotic Treatment on Cognition in Patients with Lyme Borreliosis.” Neurology, vol. 92, no. 13, Mar. 2019, pp. e1447–55. PubMed,

Berende, Anneleen, Hadewych J. M. ter Hofstede, et al. “Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease.” The New England Journal of Medicine, vol. 374, no. 13, Mar. 2016, pp. 1209–20. PubMed,

Bockenstedt, Linda K., et al. “Spirochete Antigens Persist near Cartilage after Murine Lyme Borreliosis Therapy.” The Journal of Clinical Investigation, vol. 122, no. 7, July 2012, pp. 2652–60. PubMed Central,

CDC. “Concern about Lyme Disease | CDC.” Centers for Disease Control and Prevention, 13 Jan. 2021,

—. “How Many People Get Lyme Disease? | CDC.” Centers for Disease Control and Prevention, 13 Jan. 2021,

—. “Lyme Disease Home | CDC.” Centers for Disease Control and Prevention, 19 Jan. 2022,

Chaconas, George, et al. “Changing of the Guard: How the Lyme Disease Spirochete Subverts the Host Immune Response.” The Journal of Biological Chemistry, vol. 295, no. 2, Jan. 2020, pp. 301–13. PubMed,

Clarke, Daniel J. B., et al. “Gene Set Predictor for Post-Treatment Lyme Disease.” Cell Reports Medicine, vol. 3, no. 11, Nov. 2022.,

Coburn, Jenifer, et al. “Lyme Disease Pathogenesis.” Current Issues in Molecular Biology, vol. 42, 2021, pp. 473–518. PubMed Central,

Custodio, Marco M., et al. “Disulfiram: A Repurposed Drug in Preclinical and Clinical Development for the Treatment of Infectious Diseases.” Anti-Infective Agents, vol. 20, no. 3, June 2022, p. e040122199856. PubMed,

DeLong, Allison, et al. “Estimation of Cumulative Number of Post-Treatment Lyme Disease Cases in the US, 2016 and 2020.” BMC Public Health, vol. 19, no. 1, Apr. 2019, p. 352. PubMed,

Eliassen, Knut Eirik, et al. “Symptom Load and General Function among Patients with Erythema Migrans: A Prospective Study with a 1-Year Follow-up after Antibiotic Treatment in Norwegian General Practice.” Scandinavian Journal of Primary Health Care, vol. 35, no. 1, Mar. 2017, pp. 75–83. PubMed,

Embers, Monica E., et al. “Persistence of Borrelia Burgdorferi in Rhesus Macaques Following Antibiotic Treatment of Disseminated Infection.” PLOS ONE, vol. 7, no. 1, Jan. 2012, p. e29914. PLoS Journals,

Estrada-Peña, Agustín, et al. “An Updated Meta-Analysis of the Distribution and Prevalence of Borrelia Burgdorferi s.l. in Ticks in Europe.” International Journal of Health Geographics, vol. 17, no. 1, Dec. 2018, p. 41. BioMed Central,

“Factsheet about Borreliosis.” European Centre for Disease Prevention and Control, Accessed 17 Nov. 2022.

Feng, Jie, Shuo Zhang, et al. “Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Microcolony B. Burgdorferi Persisters Which Are Sterilized by Daptomycin/ Doxycycline/Cefuroxime without Pulse Dosing.” Frontiers in Microbiology, vol. 7, 2016, p. 1744. PubMed,

Feng, Jie, Megan Weitner, et al. “Eradication of Biofilm-Like Microcolony Structures of Borrelia Burgdorferi by Daunomycin and Daptomycin but Not Mitomycin C in Combination with Doxycycline and Cefuroxime.” Frontiers in Microbiology, vol. 7, 2016, p. 62. PubMed,

Geebelen, Laurence, et al. “Non-Specific Symptoms and Post-Treatment Lyme Disease Syndrome in Patients with Lyme Borreliosis: A Prospective Cohort Study in Belgium (2016-2020).” BMC Infectious Diseases, vol. 22, no. 1, Sept. 2022, p. 756. PubMed,

Goc, A., A. Niedzwiecki, et al. “In Vitro Evaluation of Antibacterial Activity of Phytochemicals and Micronutrients against Borrelia Burgdorferi and Borrelia Garinii.” Journal of Applied Microbiology, vol. 119, no. 6, Dec. 2015, pp. 1561–72. PubMed Central,

—. “Reciprocal Cooperation of Phytochemicals and Micronutrients against Typical and Atypical Forms of Borrelia Sp.” Journal of Applied Microbiology, vol. 123, no. 3, Sept. 2017, pp. 637–50. PubMed,

Goc, Anna, Aleksandra Niedzwiecki, et al. “Anti-Borreliae Efficacy of Selected Organic Oils and Fatty Acids.” BMC Complementary and Alternative Medicine, vol. 19, no. 1, Feb. 2019, p. 40. PubMed,

Goc, Anna, Alexandra Niedzwiecki, et al. “Cooperation of Doxycycline with Phytochemicals and Micronutrients Against Active and Persistent Forms of Borrelia Sp.” International Journal of Biological Sciences, vol. 12, no. 9, July 2016, pp. 1093–103. PubMed Central,

Hammer, Christian, et al. “A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity.” Molecular Medicine, vol. 21, no. 1, Jan. 2015, pp. 26–37. Springer Link,

Hein, Tabea M., et al. “Cytokine Expression Patterns and Single Nucleotide Polymorphisms (SNPs) in Patients with Chronic Borreliosis.” Antibiotics, vol. 8, no. 3, July 2019, p. 107. PubMed Central,

Jowett, Nate, et al. “Steroid Use in Lyme Disease-Associated Facial Palsy Is Associated with Worse Long-Term Outcomes: Steroids in Lyme Disease Facial Palsy.” The Laryngoscope, vol. 127, no. 6, June 2017, pp. 1451–58. (Crossref),

Liegner, Kenneth B. “Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases.” Antibiotics, vol. 8, no. 2, June 2019, p. 72.,

Ljøstad, U., and A. Mygland. “Remaining Complaints 1 Year after Treatment for Acute Lyme Neuroborreliosis; Frequency, Pattern and Risk Factors.” European Journal of Neurology, vol. 17, no. 1, Jan. 2010, pp. 118–23. PubMed,

“Lyme Disease: What’s Actually Going on Here?” Pharmaceutical Technology, 2 Apr. 2020,

Lyon, Joanna, and Hyunuk Seung. “Genetic Variation in the ABCB1 Gene Associated with Post Treatment Lyme Disease Syndrome Status.” Meta Gene, vol. 21, Sept. 2019, p. 100589. ScienceDirect,

Murray, Lilly, et al. “Kundalini Yoga for Post-Treatment Lyme Disease: A Preliminary Randomized Study.” Healthcare (Basel, Switzerland), vol. 10, no. 7, July 2022, p. 1314. PubMed,

Parthasarathy, Geetha, and Shiva Kumar Goud Gadila. “Neuropathogenicity of Non-Viable Borrelia Burgdorferi Ex Vivo.” Scientific Reports, vol. 12, no. 1, Jan. 2022, p. 688. PubMed,

Radolf, Justin D., et al. “Lyme Disease in Humans.” Current Issues in Molecular Biology, vol. 42, 2021, pp. 333–84. PubMed Central,

Rebman, Alison W., et al. “The Clinical, Symptom, and Quality-of-Life Characterization of a Well-Defined Group of Patients with Posttreatment Lyme Disease Syndrome.” Frontiers in Medicine, vol. 4, 2017. Frontiers,

Schröder, Nicolas W. J., et al. “Heterozygous Arg753Gln Polymorphism of Human TLR-2 Impairs Immune Activation by Borrelia Burgdorferi and Protects from Late Stage Lyme Disease.” Journal of Immunology (Baltimore, Md.: 1950), vol. 175, no. 4, Aug. 2005, pp. 2534–40. PubMed,

Steere, Allen C., et al. “Antibiotic-Refractory Lyme Arthritis Is Associated with HLA-DR Molecules That Bind a Borrelia Burgdorferi Peptide.” The Journal of Experimental Medicine, vol. 203, no. 4, Apr. 2006, pp. 961–71. PubMed Central,

Strle, Klemen, et al. “A Toll-like Receptor 1 Polymorphism Is Associated with Heightened T-Helper 1 Inflammatory Responses and Antibiotic-Refractory Lyme Arthritis.” Arthritis and Rheumatism, vol. 64, no. 5, May 2012, pp. 1497–507. PubMed Central,

Vrijmoeth, Hedwig D., et al. “Prevalence and Determinants of Persistent Symptoms after Treatment for Lyme Borreliosis: Study Protocol for an Observational, Prospective Cohort Study (LymeProspect).” BMC Infectious Diseases, vol. 19, no. 1, Apr. 2019, p. 324. PubMed,

About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.

Find your next article: