Archive for the ‘Gut Health’ Category

Re-Cap of LDA/Columbia Lyme Conference

https://www.lymedisease.org/lda-columbia-lyme-conference/

LYME SCI: My re-cap of recent LDA/Columbia Lyme conference

On October 2, I attended the 21st annual scientific conference put on by the Lyme Disease Association and Columbia University’s Vagelos College of Physicians & Surgeons. The virtual event was entitled Lyme & Other Tick-Borne Diseases: Research for a Cure. 

Pat Smith, President of the Lyme Disease Association, welcomed the audience and reviewed the huge body of research the LDA has funded. A recent highlight: a paper showing that changes in the eye may serve as a biomarker for Lyme disease.

She also discussed how the CDC’s criteria for listing states as low-incidence leads to underreporting of Lyme disease. (This topic was also featured in the Summer 2021 issue of The Lyme Times.)

I especially enjoyed Pat’s introduction of Dr. Brian Fallon, of Columbia University, which included pictures and stories of their many collaborations since 1995.

The conference was divided into four sessions and was moderated by Dr. Fallon and Monica Embers, PhD, of Tulane University.

Session 1

The first speaker was John Aucott, MD, of Johns Hopkins University. He spoke on Long Haulers: Lessons from Lyme Disease, ME/CFS, and COVID-19.

Summary: The COVID-19 pandemic has drawn attention to the varied outcomes that may follow acute infectious diseases. COVID long haulers present another example of a patient group that fails to recover their normal health after the initial phase of infection has passed. Long haulers in COVID 19 and Lyme disease share many clinical features including extreme fatigue, cognitive difficulties and chronic pain. The current COVID-19 pandemic may present insights and research discoveries that help understand the underlying mechanisms involved in such persisting symptoms. Understanding the cause of these chronic symptoms is the first step to future treatments and recovery.

Dr. Aucott is currently collaborating with several of the following researchers to investigate the proposed mechanisms of chronic Lyme including: persistent infection, immune dysregulation due to by-products of past infection, auto-inflammation, auto-immunity, and neural network alteration. (I will be writing more about these mechanisms in my next article.)

Next up was Dr. Fallon’s talk: Depression, Suicidal Behaviors, and Lyme: Results from a Nationwide Study in Denmark.

Summary: This presentation reviewed the results of  Dr. Fallon’s recent U.S.- Denmark collaboration to determine whether in fact mental disorders and suicidal behaviors are increased after the diagnosis of Lyme disease. Although cases reports, small series, and office-based practice chart reviews have been published suggesting an association, these studies all had methodological limitations which left these questions unanswered.

Using a nationwide sample of people living in Denmark between 1994 and 2016 (n=6,945,837) and data from the Danish registries of hospital-based diagnoses, they investigated whether the rates of mental disorders, affective disorders, suicide attempts, and suicide were each higher after a hospital diagnosis of Lyme borreliosis compared to the rest of the Danish population without a registered diagnosis of Lyme borreliosis. They examined whether temporal proximity to the diagnosis and number of episodes increased the rates of these adverse mental health outcomes.

The researchers found that individuals with Lyme disease had a 28% higher rate of mental disorders, 42% higher rate of mood disorders and 75% higher rate of death by suicide when compared to the non-Lyme controls.

The third speaker of the morning was Ed Breitschwerdt, DVM, of North Carolina State University. He spoke on: Bartonella Bacteremia and Neuropsychiatric Illnesses.

Summary: In the past two decades, over 40 Bartonella species have been discovered, many of which have been implicated in association with a spectrum of disease in animals and human patients. The extent to which, or the mechanisms by which Bartonella infection contributes to neuropsychiatric illnesses has not been systematically studied. However, microbiological detection of the DNA of several species of Bartonella in blood supports a potential role for these bacteria in neuropsychiatric diseases such as Pediatric Acute Onset Neuropsychiatric Syndrome (PANS) and schizophrenia.

In 2021, Dr. Breitschwerdt and his lab published the initial results of a pilot study showing that out of 17 patients with schizophrenia, 12 tested positive for Bartonella in their blood. They now have funding to proceed with a larger study that will include diagnosis and treatment for Bartonella.

Q and A

At the end of Session 1, Dr. Embers moderated the questions and answers  session. I found it enlightening to have these high-level researchers and clinicians answering questions from the audience, including other scientists.

I asked a question about co-infections: “It appears both Lyme and Bartonella patients are prone to psychiatric illness. Has anyone looked at or compared the number of patients who have both? Do we know if these [Fallon study] Lyme patients have Bartonella, or do we know how many of the Bartonella patients [Breitschwerdt study] have Lyme?”

Dr. Breitschwerdt said it is important to track this and that the work coming out of his lab as well as Embers’ work is helping to elucidate. Embers added:

Borrelia may be comparable to AIDS, in its ability to suppress the immune system and these co-infections definitely warrant further study.”

Session 2

The first speaker of session two was Brandon L. Jutrus, PhD, of Virginia Tech. The title of his talk: Not just another brick in the wall.

Summary: The unusual peptidoglycan of Borrelia burgdorferi. The peptidoglycan sacculus is a mesh-like bag that protects bacterial cells from bursting. Virtually all bacteria have similar peptidoglycan structure. Borrelia burgdorferi—the Lyme disease agent— produces peptidoglycan with extremely unusual chemical features. Further, during growth, peptidoglycan is shed and is capable of causing arthritis. He discussed how the Jutras lab is exploiting the unusual properties of B. burgdorferi peptidoglycan to understand and diagnose Lyme disease.

Dr. Jutrus presented some unpublished data that may lead to an early diagnostic test and targeted treatment for Lyme.

The next speaker was Catherine A. Brissette, PhD, of the University of North Dakota School of Medicine and Health Sciences. The title of her talk: Borrelia colonization of the dura mater induces inflammation in the CNS.

Summary: “Lyme disease, which is caused by infection with Borrelia burgdorferi, can lead to inflammatory pathologies affecting the joints, heart, and nervous systems including the central nervous system (CNS). Laboratory mice have been used to define the kinetics of B. burgdorferi infection and host immune responses in other tissues, but similar studies are lacking for the CNS of these animals. Previously, we reported the ability of B. burgdorferi to colonize the dura mater of mice during late disseminated infection. We now show acute and persistent extravascular B. burgdorferi colonization of the dura mater after both needle inoculation and tick transmission, accompanied by increases in expression of inflammatory cytokines. These increases in inflammatory gene expression are similar to what is observed with B. burgdorferi stimulation of human astrocytes, microglia, brain endothelial cells, and choroid plexus epithelial cells in vitro. In addition, we observe a robust interferon response in the dura mater. Dura colonization is associated with perivascular leukocyte infiltration and meningitis, demonstrating for the first time that B. burgdorferi-infected mice can develop meningitis. We also observe an increase in interferon-stimulated genes in both the cortex and hippocampus of infected mice, despite a lack of detectable bacteria in the brain parenchyma. Combined with the increases in inflammatory gene expression and down-regulation of genes involved in maintenance of blood-brain and blood-CSF barriers in both mice and human cell culture models, these results could provide insights into the mechanism of B. burgdorferi dissemination into the CNS and the damage associated with this pathogen.”

The last speaker of Session 2 was Adrian Baranchuk, MD, FACC, FRCPC, FCCS, FSIAC, of Queen’s University in Ontario, Canada. The title of his talk: All you need to know about Lyme carditis…and more.

Summary: Lyme disease (LD) is a tick-borne bacterial infection caused by Borrelia burgdorferi. It is the most reported vector-born disease in North America, and its incidence has risen dramatically in recent years. In up to 10% of cases, bacterial dissemination of LD may lead to cardiac tissue inflammation and early disseminated Lyme carditis. The most common clinical presentation of Lyme carditis is high-degree atrioventricular block (AVB) which can progress rapidly over minutes, hours, or days. Most AVB in Lyme carditis resolves with appropriate antibiotic treatment without the need for a permanent pacemaker.

Dr. Baranchuk, encourages medical providers to do an ECG on all patients with cardiac symptoms and to consider Lyme carditis when heart block is observed.

Another Q & A

At the end of Session 2, there was another question and answer time, moderated by Dr. Fallon. Let me just say the work coming out of the labs of Dr. Jutrus and Dr. Brissette is groundbreaking. I will definitely be writing more about what I learned from this session.

Session 3

The first speaker for session three was Dr. Monica Embers, on the topic of Combined Antimicrobial Therapy for Eradication of B. burgdorferi.

Summary: Given the potential for standard antibiotic treatment regimens for Lyme disease to fail to eradicate persisters, we aim to discover a drug combination that can eliminate B. burgdorferi infection. The goals of this project are to: (1) using a library of FDA-approved drugs, identify the optimal antimicrobial combinations that could kill B. burgdorferi in vitro; and (2) test them in animal models of Lyme disease for cure of infection. The most effective combinations of drugs that kill the bacteria have been identified with in vitro studies. These were then evaluated in B. burgdorferi-infected mice, using long-term infection to allow for regrowth of persisters. Finally, the most effective regimens are being assessed in nonhuman primates. Importantly, we have refined the selection of drugs to those that can be administered orally.

Next, Kim Lewis, PhD, of Northeastern University, spoke about Developing therapies for Lyme disease.

Summary: Symptoms of Post-Treatment Lyme Disease Syndrome (PTLDS) are experienced by approximately 10% of patients after antibiotic therapy for an acute B. burgdorferi infection. The underlying causes of PTLDS symptoms have remained unclear. We reasoned that the gut microbiome may play an important role in PTLDS given the overlapping symptoms associated with a dysbiotic microbiome, including mood, cognition, and autoimmune disorders. Using sequencing data from stool of a cohort of PTLDS patients, we identified a gut microbiome signature characterized primarily by high relative abundance of Blautia species and reduction in levels of the symbiotic Bacteroides genus. These findings suggest that Lyme disease should be treated with selective antibiotics that will not harm the microbiome. We find that hygromycin A selectively kills B. burgdorferi and cures the acute disease in a mouse model without affecting the microbiome.

The last speaker for session three was Kenneth B. Liegner, MD, discussing Disulfiram in the Treatment of Lyme disease: Promise & Perils.

Summary: Some four years have elapsed since disulfiram was first knowingly applied in the treatment of persons with Lyme disease. Dr. Liegner reviewed several trial cases of patients with Lyme disease who responded positively to disulfiram. He cautioned that the drug comes with a strong warning against alcohol use/proximity, and cross-reactions to certain other medications.

Learn more about disulfiram and why is it sparking excitement in Lyme community.

Q and A

The Q&A segment at the end of session 3 was moderated by Dr. Fallon. It was really fantastic to have Dr. Liegner who has been treating Lyme patients for the past 30 years, be able to interact with these researchers who are both currently working hard to finding a cure for Lyme disease. Dr. Fallon made a point of stating the use of disulfiram is experimental and not currently approved for Lyme disease.

Session 4

Session four began with Marna Erricson, PhD, of the University of Minnesota. She spoke on Bartonella henselae Detected in Malignant Melanoma

Summary: Bartonella bacilliformis (B. bacilliformis), Bartonella henselae (B. henselae), and Bartonella quintana (B. quintana) are bacteria known to cause verruga peruana or bacillary angiomatosis, vascular endothelial growth factor (VEGF)‐dependent cutaneous lesions in humans. Given the bacteria’s association with the dermal niche and clinical suspicion of occult infection by a dermatologist, we determined if patients with melanoma had evidence of Bartonella spp. infection. Within a one‐month period, eight patients previously diagnosed with melanoma volunteered to be tested for evidence of Bartonella spp. exposure/infection. Subsequently, confocal immunohistochemistry and PCR for Bartonella spp. were used to study melanoma tissues from two patients. Blood from seven of the eight patients was either seroreactive, PCR positive, or positive by both modalities for Bartonella spp. exposure. Subsequently, Bartonella organisms that co‐localized with VEGFC immunoreactivity were visualized using multi‐immunostaining confocal microscopy of thick skin sections from two patients. Using a co‐culture model, B. henselae was observed to enter melanoma cell cytoplasm and resulted in increased vascular endothelial growth factor C (VEGFC) and interleukin 8 (IL‐8) production. Additionally, the two tissues also were found to have BRAF mutations, an oncogene expressed in up to 70% of melanomas. Findings from this small number of patients support the need for future investigations to determine the extent to which Bartonella spp. are a component of the melanoma pathobiome. Being at the frontier of understanding the role of the microbiome in cancer, we will discuss some new papers on this topic and future research plans.

The final speaker of the day was, Richard Maggi, PhD, North Carolina State University. His topic: Simultaneous detection and absolute quantification of Babesia, Bartonella and Borrelia by droplet digital PCR.

Summary: This presentation describes the development, optimization, and validation of a ddPCR assay for the simultaneous detection of Babesia, Bartonella, and Borrelia spp. DNA from several sample matrices, including clinical blood samples from animals and patients, vectors (ticks, fleas, sandflies), as well as samples from human and animal cell lines and tissues from animal models (infected with Bartonella and/or B. burgdorferi). The multiplex ddPCR assay (BBB ddPCR), developed based upon a recently published a Bartonella ddPCR assay using the QX200 system from Bio-Rad, is able to detect 31 Bartonella spp. (including 8 previously uncharacterized species), 8 Borrelia spp, and 24 Babesia spp. (including 8 previously uncharacterized species). The assay is also able to detect 2 Theilaria spp. (T. equi and T. cervi) and well as C. felis from naturally infected wildlife species. The BBB ddPCR assay, based on the QX One ddPCR system from Bio-Rad, showed to be able to perform the simultaneous detection and absolute quantification of multiple vector-borne pathogens (such as Babesia, Bartonella and Borrelia) from clinical samples.

Q & A

The Q&A at the end was moderated by Dr. Embers. The research presented by these two was highly technical, but I can say their work will provide better diagnostics that will lend to each of the previous researcher work.

LymeSci is written by Lonnie Marcum, a Licensed Physical Therapist and mother of a daughter with Lyme. She serves on a subcommittee of the federal Tick-Borne Disease Working Group. Follow her on Twitter: @LonnieRhea  Email her at: lmarcum@lymedisease.org.

Do an Altered Gut Microbiota and an Associated Leaky Gut Affect COVID-19 Severity?

https://journals.asm.org/doi/10.1128/mbio.03022-20?

mBio

Volume 12, Number 1
23 February 2021
 
ABSTRACT
 
Coronavirus disease 2019 (COVID-19), which has been declared a pandemic, has exhibited a wide range of severity worldwide. Although this global variation is largely affected by socio-medical situations in each country, there is also high individual-level variation attributable to elderliness and certain underlying medical conditions, including high blood pressure, diabetes, and obesity. As both elderliness and the aforementioned chronic conditions are often associated with an altered gut microbiota, resulting in disrupted gut barrier integrity, and gut symptoms have consistently been associated with more severe illness in COVID-19 patients, it is possible that dysfunction of the gut as a whole influences COVID-19 severity. This article summarizes the accumulating evidence that supports the hypothesis that an altered gut microbiota and its associated leaky gut may contribute to the onset of gastrointestinal symptoms and occasionally to additional multiorgan complications that may lead to severe illness by allowing leakage of the causative coronavirus into the circulatory system.
 

For more: 

GI Issues With Lyme Disease

https://www.globallymealliance.org/blog/gastrointestinal-issues-with-lyme-disease

When patients consider taking long-term antibiotics for persistent Lyme disease, they need to weigh risks and benefits of treatment. Gastrointestinal risks can include the possibility of a C.diff infection, or candidaovergrowth, which is a yeast infection that occurs not just in typical places you imagine but also in the gut. A good Lyme Literate Medical Doctor (LLMD) will put a patient on probiotics and a specific diet to mediate these risks, or may decide to go the intravenous route to take pressure off the gut.

Medication is not the only way that the gut can be impacted by Lyme disease; the infection itself can cause gastrointestinal issues. In his book How Can I Get Better? An Action Plan for Treating Resistant Lyme & Chronic Disease, Richard I. Horowitz, MD notes that Lyme and co-infections can cause inflammation leading to issues such as abdominal pain, nausea, gas, bloating, constipation, diarrhea, or reflux disease, with occasional vomiting. He writes, “…a review of gastrointestinal and liver problems associated with tick-borne diseases found that in 5 percent to 23 percent of those with early Lyme borreliosis, patients presented with varied gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, anorexia with loss of appetite, and hepatitis, and some even had symptoms of an enlarged spleen and liver.”[i] And that’s just in early Lyme—in later stages of the disease, spirochetes(Lyme bacteria) can burrow deeper into the gastrointestinal tract, causing more damage. Other tick-borne diseases can also cause their own gastrointestinal issues, often overlapping with Lyme symptoms when the patient is co-infected.

Because every case of tick-borne illness is different, some Lyme patients may not experience any gastrointestinal symptoms. When I was at my sickest with Lyme disease, babesiosis, ehrlichiosis, possible bartonella, and chronic active Epstein-Barr virus, I used to joke, “Well, at least my stomach feels okay.” Because I wasn’t experiencing abdominal pain or vomiting, I figured my stomach was the one part of my body that had gotten off easy.

In fact, many of the symptoms I experienced in other parts of my body, including joint and muscle pain, migraine headaches, fever, and fatigue, were directly related to weakness in my gut caused by disease. Unbeknownst to many people—myself included before I got sick—the gut is a major player in the immune system. Dr. Horowitz writes that the “GI tract houses 80 percent of our immune system and 70 percent of our lymphocytes, making it the first line of defense against infections.” He goes on to explain that “…the gut can hold as many as 100 trillion microbes, referred to as the microbiome.” The bacteria in each person’s unique microbiome “help to supply essential vitamins; fight dangerous pathogens; keep the immune system in balance and modulate autoimmune disease (like MS and rheumatoid arthritis); modulate hormones, appetite, weight, glucose metabolism, and diabetes; modulate cardiovascular risk, neurological and psychiatric diseases (like Parkinson’s and schizophrenia); affect epigenetics, modulate cancer risk and affect inflammatory reactions in the body, including allergies, asthma, Crohn’s disease, and colitis.”i

An imbalanced microbiome can lead to intestinal permeability, commonly called “leaky gut syndrome.” This can allow toxins pass into the gut, causing inflammation and changes in flora; it’s similar to what happens when the blood-brain barrier is compromised. A 2020 study done by researchers at Johns Hopkins University School of Medicine, Northeastern University, and University of California San Diego found that the gut microbiome of post treatment Lyme disease patients was distinctly different than the gut microbiome of healthy subjects.

Whether Lyme patients experience gastrointestinal symptoms or not, their microbiome is impacted by their infection(s), their medications, and their diet. A weakened microbiome means a weakened ability to heal. As Lyme patients, we can help strengthen our microbiome by taking probiotics to replace good bacteria that are killed by antibiotics (some patients also take an anti-fungal medication, which can have anti-spirochetal effects, too), and by sticking to “The Lyme Diet.” Gluten and sugar are particular menaces to the microbiome, and your doctor may also recommend other dietary changes or nutritional supplements to help you maintain gut health. As I’ve come to learn, it is central to overall health!

[i] Horowitz, Richard I., MD. How Can I Get Better? An Action Plan for Treating Resistant Lyme & Chronic Disease. New York: St. Martin’s Griffin, 2017 (327, 328-9).

Abdominal Pain, Ileus & Constipation Due to Lyme Disease

https://danielcameronmd.com/abdominal-pain-constipation-lyme-disease/  Podcast here

ABDOMINAL PAIN, ILEUS AND CONSTIPATION DUE TO LYME DISEASE

doctor examining woman with abdominal pain due to lyme disease

Welcome to another Inside Lyme Podcast. I am your host Dr. Daniel Cameron. In this episode, I will be discussing the case of a 65-year-old woman with abdominal pain, ileus/pseudo-obstruction and constipation due to Lyme disease.

Zulfiqar and colleagues first described this case in an article entitled “The many manifestations of a single disease: neuroborreliosis,” published in the Journal of Community Hospital Internal Medicine Perspectives.¹

A 65-year-old woman on hormonal therapy for estrogen receptor-positive breast cancer presented to the Emergency Department with sudden seventh nerve palsy, commonly referred to as Bell’s palsy.

One week prior, she began having burning back pain radiating to the abdomen, which had grown worse and over the past several months had suffered from constipation.

Stroke, herpes virus or Lyme disease?

The woman was admitted to the hospital for a suspected stroke. However, there was no evidence of a stroke by brain CT or MRI.

Doctors also suspected she had a herpes zoster infection and prescribed valacyclovir, an anti-viral medication.

The patient worked frequently in her backyard and was exposed to wooded areas. She also recalled having a rash on her stomach 11 days before being admitted to the hospital.

“Lyme serum antibody (IgG and IgM) was positive with confirmatory Western blot resulting in multiband reactivity,” the authors write. Spinal tap test results were also positive for Lyme disease.

The woman was diagnosed with neuroborreliosis, or Lyme disease and treated with oral doxycycline.

However, while hospitalized the patient developed diffuse abdominal pain, abdominal distension, and worsening constipation.

An abdominal x-ray showed mild ileus. “CT abdomen with contrast was done which suggested constipation without obstruction or ‘significant’ ileus,” the authors explain. A colonoscopy was also normal.

The woman was also diagnosed with Syndrome of Inappropriate Anti-diuretic Hormones (SIADH) based on a sodium of 129 and typical urine findings.

Abdominal pain, gastrointestinal problems in Lyme disease

The authors highlight several studies demonstrating a range of gastrointestinal problems, including abdominal pain, associated with Lyme disease.

“There have been many case reports in the past highlighting the atypical presentation of Lyme disease including, but not limited to pseudo-obstruction, constipation, back pain radiating to abdomen (radiculoneuritis) known as Bannwarth Syndrome as a manifestation of autonomic dysfunction related to neuroborreliosis,” the authors explain.

This patient also suffered from anorexia with a loss of 14 pounds. One study found that 23% of 314 patients with early Lyme disease suffered from anorexia.

Meanwhile, Shamim et al. reported two cases of patients who presented with severe constipation and hyponatremia in addition to other features of Lyme disease.

Lyme neuroborreliosis has also been reported as “the culprit of chronic intestinal pseudo-obstruction” in other studies, the authors explain. “The patients can develop worsening constipation and obstipation as diagnosis and treatment is delayed, leading to diffuse bowel dilation in the absence of mechanical obstruction.”

Lastly, “There have been a few case reports of SIADH associated with neuroborreliosis,” writes Zulfiqar.

Authors’ Conclusion: Lyme disease should be suspected in patients who are from Lyme endemic areas and present with abdominal pain, constipation and SIADH with or without cranial nerve palsy.

The following questions are addressed in this podcast episode:  

  1. Why was a stroke initially considered?
  2. Why was herpes zoster suspected?
  3. What are the causes of 7th nerve palsy?
  4. What is SIADH?
  5. What is ileus?
  6. What is Bannwarth Syndrome?
  7. How are GI issues related to autonomic dysfunction?

    Thanks for listening to another Inside Lyme Podcast. You can read more about these cases in my show notes and on my website @DanielCameronMD.com. As always, it is your likes, comments, reviews, and shares that help spread the word about Lyme disease. Until next time on Inside Lyme.

Please remember that the advice given is general and not intended as specific advice to any particular patient. If you require specific advice, then please seek that advice from an experienced professional.

Inside Lyme Podcast Series

This Inside Lyme case series will be discussed on my Facebook page and made available on podcast and YouTube.  As always, it is your likes, comments, and shares that help spread the word about this series and our work. If you can, please leave a review on iTunes or wherever else you get your podcasts.

References:
  1. Zulfiqar S, Qureshi A, Dande R, Puri C, Persaud K, Awasthi S. The many manifestations of a single disease: neuroborreliosis. J Community Hosp Intern Med Perspect. Jan 26 2021;11(1):56-59. doi:10.1080/20009666.2020.1831746

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For more:

Clinical Considerations of Clostridia Bacterial Concerns

https://biocidin.wistia.com/medias/wxusy0cfns Go here for presentation (Approx 22 Min)

Part 1: Clinical Considerations of Clostridia Bacterial Concerns – Pathogenicity Mechanisms

Biocidin Education Series

For more: