Show 1455: Common Culprits: How Infections Trigger Chronic Diseases

When doctors talk about infections, they are usually referring to acute situations in which the immune system gets overwhelmed by a virus such as influenza or chickenpox. Infections also result from the interaction of bacteria with the immune system, as in the case of pneumonia or sepsis. These can be crises, but they are relatively short-lived, resolving one way or the other within a few weeks or at most months. Could infections trigger chronic diseases? Our guest, evolutionary biologist Dr. Paul Ewald, thinks they do.

At The People’s Pharmacy, we strive to bring you up to date, rigorously researched insights and conversations about health, medicine, wellness and health policies and health systems. While these conversations intend to offer insight and perspective, the content is provided solely for informational and educational purposes. Please consult your healthcare provider before making any changes to your medical care or treatment.

How Infections Trigger Chronic Diseases:

Investigating the origins of chronic diseases requires a great deal of patience and the ability to examine several different areas that might be relevant. Over the past few decades, the technology for evaluating genetic contributions has improved greatly. What we have learned is that most chronic conditions are associated with a range of genes that each add a small amount of risk.

To get further insight, we have to look at the environment. This broad area includes topics as far ranging as sunshine, stress and nutrition. In particular, we need to look at the pathogens present in any given environment, as they could play an important role in our health.

Scrutinizing the environment is not enough. To understand the impact on disease, we need to know more about human behavior within that environment. How much sun exposure do the patients get? Are they sleeping? Where do they spend most of their time, and with whom? These all will help us understand the link to pathogens.

What We Have Learned About the Microbiome:

Over the past several decades, scientists have learned a great deal about the microbiome. The original conception of gut bacteria has been enriched with the understanding that almost every part of the human body has its own microbiome, almost as unique as a fingerprint. These collections of microbes live in harmony–or disequilibrium–with microbes from the environment. Some of these may be beneficial. Others undoubtedly are harmful, and we call them pathogens. How do pathogens trigger chronic diseases?

How Does the Body React to Pathogens?

When pathogens are detected, the immune system responds. Often, that comes in the form of macrophages, immune cells that circulate in the blood and attack the pathogens. Even a type of microbe that normally cohabits peacefully with the others in its space can cause trouble if it becomes too numerous or goes out of bounds. One example is Porphyromonas gingivalis. It’s usually found in the mouth. If it gets too exuberant there, it can cause gum disease. Worse, though, the macrophages dispatched to deal with P. ginigivalis anywhere in the body can end up collecting in atherosclerotic plaque in arteries (Signal Transduction and Targeted Therapy, May 23, 2025).

Another example of pathogens causing unexpected trouble is Clostridium (or Clostridioides) difficile (C. diff). These bacteria can live among other gut microbes and you might not even know they were there. But if the microbiota become disturbed, from a course of antibiotic treatment, for example, C. diff can proliferate and cause terrible diarrhea that may be very difficult to treat. Studies indicate that C. diff has evolved so that the strains in hospitals are now more likely to be resistant to antibiotic medications.

Alzheimer disease seems like a chronic condition rather than a complication of infection. Certainly, researchers have been examining genetic predispositions for the accumulation of beta-amyloid plaque in the brain. Yet Alzheimer disease is associated with microbes such as Chlamydia pneumoniae and P. gingivalis. Could flossing your teeth to reduce your chance of periodontal disease also help lower your risk of Alzheimer disease? Recent research has shown that older people receiving the shingles vaccine are less likely to be diagnosed with dementia. Perhaps amyloid plaques in the brain are part of an immune response to infection.

Has Long COVID Shifted Our Perspective on Chronic Disease?

Several decades ago, The People’s Pharmacy interviewed Dr. Paul Cheney, then of Incline Village, Nevada, about his patients with chronic fatigue syndrome. He believed at the time that epidemiological patterns of this mysterious illness pointed to an infectious origin. Years have passed, and no pathogen has been identified to satisfy the criteria as THE cause of myalgic encephalomyelitis (ME/CFS).

Recently, though, millions of Americans have been struggling with a condition that seems rather similar. The only difference is that we know their symptoms began with a COVID-19 infection. Long COVID is difficult to treat. Patients suffering with this condition appear to be afflicted with a serious chronic disease. Researchers have not always found evidence of persistent infection with the SARS-CoV-2 virus. Nonetheless, in most cases a COVID infection was clearly the origin. How has that changed our attitude toward the possibility that infections trigger chronic diseases?

Other Mystery Conditions:

As we contemplate the possibility that infections trigger chronic diseases, we should not overlook chronic Lyme disease. Most infectious disease experts insist it isn’t an infection. Some even resist the idea that people are suffering. Dr. Ewald suggests that perhaps the inability to identify pathogens in the wake of Lyme disease is due to using old techniques.

The pathogens don’t show up on these tests, but that could be because they are hiding. Will newer techniques reveal them? What about the possibility that diseases like arthritis or schizophrenia are caused by pathogens in some cases? The evidence is tantalizing. Dr. Ewald urges us to look at the chronic phases of infection as well as the acute phases.

This Week’s Guest:

Paul Ewald, PhD, is an evolutionary biologist, specializing in the evolutionary ecology of parasitism, evolutionary medicine, agonistic behavior, and pollination biology. He is currently a Professor of Biology at the University of Louisville. Professor Ewald is a pioneer in evolutionary medicine and infectious disease research. He has challenged conventional wisdom on the causes and prevention of many chronic diseases with his idea that many diseases of unknown origin are the result of chronic low-level infections, which has ultimately been shown to be correct for a wide range of diseases to date. He is the author of Evolution of Infectious Disease and Plague Time: The New Germ Theory of Disease.

The People’s Pharmacy is reader supported. When you buy through links in this post, we may earn a small affiliate commission (at no cost to you).

Paul Ewald, PhD, describes how microbes evolve

Citations

• Huang X et al, "Porphyromonas gingivalis aggravates atherosclerotic plaque instability by promoting lipid-laden macrophage necroptosis." Signal Transduction and Targeted Therapy, May 23, 2025. DOI: 10.1038/s41392-025-02251-6