Introduction
Lyme disease is caused by members of the Borrelia burgdorferi sensu lato complex and is the most common vector-borne bacterial infection in the Northern Hemisphere. The clinical presentation of the disease is diverse, ranging from the characteristic erythema migrans rash to joint, neurological and cardiovascular manifestations. In recent years, there has been an increasing amount of research investigating how the infection directly or indirectly affects the body’s microbiome, particularly in the gut and skin.
The microbiome is the collection of trillions of microorganisms living in the human body, which plays a key role in regulating the immune system, metabolic processes and defence against pathogens. Changes in the composition of the microbiome (dysbiosis) have been linked to a number of medical conditions, such as inflammatory bowel disease, metabolic syndrome and autoimmune disorders. In the case of Lyme disease, there is also growing evidence that infection and its antibiotic treatment cause significant changes in the microbiome, which may have clinical consequences.
Human studies: microbiome changes in Lyme infection
Human studies are less available, but some clinical studies have reported differences in the composition of the gut flora in patients with Lyme infection. The most common phenomenon is a decrease in the proportion of beneficial bacteria, while certain opportunistic species relatively overgrow.
These changes are often accompanied by damage to the intestinal barrier function, which can result in increased antigen load and systemic inflammatory response. Based on human data, a decline in the Bacteroides genus and a predominance of certain members of the Firmicutes phylum (e.g. Blautia) are characteristic, which is consistent with microbiome patterns observed in other inflammatory conditions.
Some researchers have suggested that the use of probiotics or prebiotics may help restore the microbiome during and after infection or antibiotic treatment, but their effectiveness in Lyme disease patients has not yet been tested in large clinical trials.
Animal models: exploring mechanisms
Changes in the gut microbiome
In addition to human data, animal models are particularly valuable because they allow the effects of infection and treatment to be studied under controlled conditions. In a study published in 2025, rhesus macaques were infected with Borrelia burgdorferi, and then some of them received antibiotics while others remained untreated.
The results showed that the infection itself caused changes in the microbiome, including a decrease in butyrate-producing bacteria and modulation of the immune response. In infected and treated animals, the effects were cumulative, meaning that both the infection and the treatment contributed to the development of dysbiosis.
Human implications
Lyme disease and the resulting autoimmune response often attack the nervous system. This is also true for the parasympathetic nerve fibres that innervate the intestinal tract, which, as part of the gut-brain axis, regulate intestinal peristalsis, among other things. Spasms caused by nerve fibres slow down or even disrupt the passage of stool. As a result, food digestion changes, which can alter the microflora of the small intestine or other sections of the intestine. In the case of the small intestine, a decrease in the speed of intestinal transit can cause pathological superinfections, displacing the limited amount and diversity of beneficial bacteria present there (small intestinal bacterial overgrowth, SIBO), and in healthy sections of the intestine, it can cause quantitative shifts in the normal intestinal flora bacteria, thus indirectly influencing the effects of nutrition (e.g. weight loss/obesity, nutrient deficiency).
SIBO is a relatively new concept, and laboratory testing for it has only gained ground in recent years, so few studies are available on the relationship between Lyme disease and small intestine infections and imbalances. The latest publications mention a significantly higher prevalence of SIBO than expected or previously measured. Although doctors treating Lyme disease are increasingly observing this phenomenon, the only clinical research on the subject has not confirmed a higher prevalence of SIBO among patients diagnosed with Lyme disease. However, it is important to note that SIBO is not an independent cause, but a consequence of associated factors such as reduced immunity, altered bowel movement (gastroparesis, intestinal pseudo-obstruction), hypothyroidism and infection, which are also factors in Lyme disease.
Changes in the gut microbiome are therefore a multifactorial process that is an expected consequence of Lyme disease. Thus, in order to ensure the effectiveness of treatment and alleviate symptoms, a comprehensive gut flora examination is recommended, including quantitative testing for fungi, parasites, commensal and infectious bacteria, the cultivation and antibiotic sensitivity of pathogenic bacteria, the proportion of beneficial intestinal bacteria, and the permeability of the intestinal wall. This is particularly recommended in cases where the patient will undergo repeated treatment.
The role of the skin microbiome
The skin is the primary entry point for Lyme infection. In a 2023 in vitro study, Baquer and colleagues examined how human keratinocytes and fibroblasts respond to skin commensal bacteria when they are present together with Borrelia components.
The results showed that bacteria living on the skin—such as Staphylococcus epidermidis, Corynebacterium striatum, and Cutibacterium acnes—are able to increase the production of inflammatory cytokines (IL-8, CXCL1, MCP-1) in the presence of Borrelia components. This suggests that the skin microbiome actively influences the body’s initial immune response to Borrelia invasion and may thus play a role in the outcome of the infection.
Effect of antibiotics on the microbiome during Lyme treatment
The treatment of Lyme disease is primarily based on broad-spectrum antibiotics. The most commonly used agents include doxycycline, amoxicillin, cefuroxime and, in more severe cases, ceftriaxone. Although these preparations effectively eliminate Borrelia bacteria, their use can also have a significant impact on the host’s microbiome.
Numerous studies have shown that even a few weeks of antibiotic therapy can dramatically reduce the microbial diversity of the gut. Antibiotics have a particularly sensitive effect on bacteria that produce anti-inflammatory short-chain fatty acids such as butyrate (e.g. Faecalibacterium prausnitzii, Roseburia species). The disappearance of these bacteria can lead to long-term digestive problems, increased intestinal permeability and changes in the host’s immune system.
In a 2025 animal study, Napier and Messaoudi’s research group studied rhesus macaques treated with antibiotics and showed that antibiotic treatment alone significantly reduced the number of butyrate-producing microorganisms in the intestine while increasing inflammatory signalling. This finding highlights that dysbiosis as a side effect of Lyme therapy may be an independent risk factor for subsequent health problems.
It is worth noting that some bacteria that infect the gut flora can also produce toxins, which increase toxin production when exposed to antibiotics, thus potentially affecting the kidneys or liver (e.g. Shiga toxin-producing bacteria).
Clinical and research implications
Based on current data, the relationship between Lyme disease and the microbiome manifests itself on several levels:
- Antibiotic effect – standard therapy drastically alters the intestinal flora, especially the beneficial butyrate-producing communities.
- Infection effect – Borrelia itself is capable of influencing the microbial ecosystem of the gut.
- Role of the skin microbiome – in the early stages of infection, the skin flora can exacerbate the inflammatory response.
Together, these factors may contribute to the clinical diversity of Lyme disease and its systemic consequences. However, many questions remain unanswered: we do not know exactly how much microbiome changes contribute to clinical symptoms, or how these processes can be therapeutically influenced.
Future research should focus on the following areas:
- investigation of interventions aimed at restoring the microbiome (probiotics, prebiotics, dietary interventions);
- long-term human follow-up studies to clarify the process of microbiome reconstitution after infection and treatment;
- exploring the relationship between the skin microbiome and infection outcomes.
Summary
The relationship between Lyme disease and the microbiome is therefore complex and determined by multiple factors. Antibiotic therapy and the infection itself cause significant changes in the gut flora, which may have long-term effects on the host’s immune system function and health. In addition, the skin microbiome is actively involved in shaping the inflammatory response in the early stages of infection. Although a precise understanding of the clinical consequences requires further investigation, current data highlight that the microbiome is closely linked to the pathogenesis of Lyme disease.
Sources:
(C) Lyme Borreliosis Foundation
