PART 1: The complexities of the gut microbiota in Long COVID and understanding terminology

I'm finally able to share my latest insights as of March 2024, drawn from my extensive clinical experience with hundreds of long COVID patients. In this new series of blog posts, I will simplify some of the science from my primary focus that zeroes in on the gut microbiota.

For those of you who have been following me, you will know that my microbiome research intensified after my son's successful battle with post-sepsis syndrome. I delved into every available paper I could, and when Covid-19 hit, I discovered many similarities between the post-sepsis microbiome and what I saw and continue to observe in long COVID cases. This realisation propelled me into scientific research circles, where I've been immersed ever since.  I continue to explore hypotheses and form collaborations, with a view to gaining further insights. Along the way, I've developed a profound appreciation for conventional medicine's efforts in trying to address Long COVID, while also advocating for the consideration of nutraceuticals and natural alternatives. It's clear that medicine alone can't address nutritional deficiencies or restore a compromised microbiota.

In my clinical practice, I have chosen to prioritise conducting a thorough examination of each client's health history and timeline as opposed to prescribing off the shelf protocols and interventions that have been proposed to support recovery. With my education, ongoing research, and hands-on experience, I'm able to interpret nutritional blood work, microbiome analyses, metabolomics, and nutrigenomics. This comprehensive understanding serves as the foundation of my approach, guiding the creation of personalised dietary and lifestyle interventions. While there's no one-size-fits-all protocol for Long COVID, focusing on nutritional health alongside microbiota balance plays a vital role in the recovery process.

After four years of clinical practice with Long COVID patients, I've made several key observations:

1. There's no magic pill or protocol that universally heals Long COVID

2. There is not one single diagnostic marker that applies to Long COVID

3. Addressing nutritional deficiencies and promoting microbiota health is a crucial aspect of recovery

4. Outcomes depend on various factors, and include overall health, metabolism, epigenetics, and microbiota health (among many other components)

To make the wealth of information more accessible, I have broken my blog posts into 3 parts. This will make for easier reading, and provide the layers of information relevant to the complex interplay between the Microbiota and Long COVID.

Part 1: Introduction to the complexities of the gut microbiota and understanding terminology

Part 2: The Long Covid microbiota phenotype

Part 3: What you can do to support your gut microbiota 

Microbiome research is big business

Some 25 years ago when I first started my journey into understanding the gut microbiota, it was a time that labelled this concept as complete nonsense. There were not many studies to be found on PubMed and much of the information was coming from the alternative medicine field of practice and age old naturopaths.  Fast forward to 2024 and the microbiome has become mainstream and funding for microbiome research has increased significantly. Large corporations such as Danone and Nestle have invested billions into microbiome research and technology, which includes gene editing like CRISPR for enhancing the effects of beneficial bacteria, bacteriophage therapy to target harmful pathogens, and exploring a microbiome's role in cancer therapy and neurological disorders such as Alzheimer’s and Parkinson’s disease. Another vital area of research is understanding medication-microbiome interactions which will be discussed in more detail in a future post.

Getting the terminology right

A MICROBIOME is a collection of bacteria, viruses, yeasts, and microscopic parasites that live in a community together.  You may also hear the word MICROBIOTA, and this is the correct term used to describe microbial communities found in or on a living host. Most of the microbiome research has been done on the gut microbiota, however there are microbiota communities found in and on most areas of the human body.

When I talk to my clients about the microbiota in the gut,  I ask them to envisage it in the same way as a vegetable patch:

1. You need good quality soil. This represents the health of the gut lining and the protective mucus that it secretes.

2. You need to have seeds that germinate and grow. This represents the beneficial gut microbes or PROBIOTICS that grow in the gut.

3. You need to feed the seeds the right components for them to grow. This represents the components from our food intake called PREBIOTICS

4. If you have all these components in place, the seeds will grow and produce nutrients and other beneficial components.  This represents POSTBIOTICS which go on to have other functions in the body.

Also see figure 2

What the gut microbiota does?

Studies and experiments have revealed a multitude of functions related to the microbes particularly in the gut and these include:

o   Modulating the immune system

• Protects against allergy development.

• Helps train the immune system

• Helps support immune tolerance

• Provides a line of defence against foreign invaders

• Protects against pathogenic microbe colonisation

o   Supports normal gut motility

• Helps support the movement of food then stools through the digestive tract

• Sends signals to special cells that release important neurotransmitters that aid peristalsis (muscle contraction of the gut)

o   Improves nutritional status.

• Produce B Vitamins, biotin and vitamin K2

• May help to improve mineral absorption (calcium, magnesium and possibly zinc)

• Energy salvaging by fermenting fibers and complex carbohydrate to produce metabolites that can be used as energy

o   Regulates the gastrointestinal integrity supports the health of the gut lining

o   Supports kidney health

o   Supports xenobiotic metabolism

A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism

• Polyphenols

• Pharmaceuticals

• Pesticides / herbicides / mycotoxins

o   Produce microbial metabolites that support

• The cardiovascular system

• The mitochondria

• The liver

• The urinary system

• The nervous system and brain

An example showcasing the complexities of the gut-brain axis emerged in an excellent scientific review published in 2023. Researchers meticulously analysed data from the CAS Content Collection, which houses the largest collection of scientific literature. Their aim was to dissect the evolving landscape of gut-brain axis research in the context of gut health and mental health. Figure 1 highlights the important connection they found between the metabolites produced by the microbiota and their involvement in the health of the brain.

Figure 1 : Gut microbiome metabolites

Sasso, J. M., Ammar, R. M.,et al. (2023). Gut Microbiome-Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders. ACS Chemical Neuroscience, 14(10), 1717–1763.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197139/

Intestinal permeability 

As you will see in figure 2, the lining of gastrointestinal tract is made up of epithelial cells which form a barrier between the hosts internal environment and the digestive tract. The lining also contains goblet cells that secrete mucus, this mucus forms a layer over the epithelial cells that prevents microbes making permanent contact with the intestinal epithelial cells.  The mucus layer is constantly being turned over, with specific molecules and microbes playing a role in the break down, regeneration and protection of this mucus layer.

The cells of the digestive tract are held together by many tight junction proteins and one of those tight junction proteins is called Zonulin which will be discussed in further detail later. These tight junction proteins allow for just enough intestinal permeability for the passage of vital nutrients, fluids, and gut derived metabolites, while blocking the passage of foreign invaders from entering the blood stream.

Figure 2: Schematic of the intestinal epithelial barrier. Adapted by BeNourished from Paray, 2020

Paray, B.A.; Albeshr, M.F.; Jan, A.T.; Rather, I.A. Leaky Gut and Autoimmunity: An Intricate Balance in Individuals Health and the Diseased State. Int. J. Mol. Sci. 2020, 21, 9770. https://doi.org/10.3390/ijms21249770

Intestinal permeability is often referred to as "leaky gut," and is a condition whereby the lining of the intestines becomes more porous than normal. In my view, it's crucial to grasp the true meaning behind the term intestinal permeability, as I believe it has been somewhat misrepresented in the blogosphere.

As previously mentioned, the intestinal wall is meant to be slightly permeable because it must allow for the passage of fluids, nutrients, and certain gut metabolites, so I prefer to use the term INTESTINAL HYPERPERMEABILITY which describes the condition more clearly.

INTESTINAL HYPERPERMEABILITY is thought to occur when the protective mucus layer breaks down. Several factors can contribute to this, including certain foods, chemicals, chronic stress, long-term use of medications, viruses, and other pathogens. These factors contribute to gut dysbiosis, which refers to an imbalance within the microbiota causing changes in its structure and function, that are ultimately detrimental to the host. Dysbiosis can also contribute to the displacement and overproduction of tight junction proteins, causing the gaps between the epithelial cells to widen. This allows larger molecules, such as toxins, bacteria, and undigested food particles, to "leak" into the bloodstream.

The immune system identifies these larger molecules as foreign invaders and activates inflammatory processes. Over time, this may lead to chronic low-grade activation of the immune system and chronic low-grade inflammation. This mechanism is thought to contribute to a range of health issues, including digestive problems, food sensitivities, autoimmune diseases, and even a decline in mental health. More details will be provided in Part 2 regarding my proposed hypothesis on this mechanism in the context of Long COVID. See Figure 3.

Figure 3: Schematic presentation of intestinal hyperpermeability in Long COVID

Other important terms to familiarise yourself with

Lipopolysaccharides (LPS)

LPS are large molecules found in the outer membrane of gram-negative bacteria, such as Escherichia coli (E. coli), Salmonella, and Pseudomonas.

LPS is also know as an endotoxin. This means that when it is released into the bloodstream, it can trigger an inflammatory response. In very high levels LPS can lead to fever, septic shock, and even organ failure in severe cases.

In the context intestinal hyperpermeability, LPS can translocate from the gut into the bloodstream in lower levels as described above. Translocation of low levels of LPS have been implicated in various chronic inflammatory conditions, including metabolic syndrome, cardiovascular disease, and neurodegenerative disorders. My next blog post will describe my hypothesis on the role of LPS in Long COVID.

Bacteriophages

Bacteriophages, or phages for short, are viruses that specifically infect and replicate within bacteria. These microscopic entities are abundant in nature and play a significant role in shaping bacterial populations and ecosystems.

Phages consist of a protein coat, or capsid, which encapsulates their genetic material, either DNA or RNA. They come in various shapes and sizes, ranging from simple filamentous structures to complex icosahedral heads with elaborate tail structures.

Upon encountering a susceptible host bacterium, a phage attaches to the bacterial surface and injects its genetic material into the cell. Once inside, the phage hijacks the bacterial machinery to replicate its own DNA or RNA, ultimately leading to the production of new phage particles.  Phages can influence the composition and function of the gut microbiome by selectively targeting certain bacterial species, thereby shaping microbial communities and ecosystem stability.

In addition to their role as natural predators of bacteria, bacteriophages have gained increasing attention for their potential therapeutic applications. Phage therapy involves the use of specific phages to target and eliminate pathogenic bacteria, offering a potential alternative to traditional antibiotics in the era of antibiotic resistance.

Recent controversial research suggests that SARS-CoV-2 could function as a bacteriophage within the human microbiota. This hypothesis proposes that the virus disrupts protective bacterial species and produces harmful peptides, contributing to the prolonged effects of Long COVID. Whilst many people in the scientific community dismiss this notion as highly improbable, they fail to present a concrete counterargument as to why this mechanism would be an impossibility. In my view, this hypothesis makes perfect sense and dismissing innovative ideas without exploring their potential, limits our ability to think creatively and hinders progress towards effective healing strategies.

Join me next week for part 2 when I will describe the Long COVID microbiome phenotype that I have classified through 4 years of testing, research and clinical experience.

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COMING SOON

A series of educational webinars are soon to be released specifically for the many people who are unable to work with me and for practitioners who are struggling to see improved outcomes in their Long COVID clients. Subjects that will be covered include:

• Supporting microbiome health in Long COVID

• Practical interventions to support PoTS, MCAS and Histamine Intolerance

• An effective clinical roadmap for supporting chronic illness

About Rachel

Rachel is a registered Naturopathic Nutritionist and holds a Masters Degree in Nutrition, she has a keen interest in science and nature. Rachel has been in clinical practice for 14 years and has developed a passion for supporting people with chronic health conditions.

Activities

• Active member of the Long Covid Coalition 2020 - 2023

• Scientific advisory board member for the Long Covid-19 Foundation

• Scientific advisory board member for SpinQ Biophysics Inc

• Research collaboration with numerous peers from around the world

• Runs a busy online clinic