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Disease-causing microbes are often found in the human microbiome. So, when does the presence of pathogenic microbes indicate an infection? And when does the presence of infection explain disease?
What is an infection? What is a disease?
A disease associated with microbes is the outcome of interaction(s) between a microbe(s) and its host in which the host suffers some sort of damage. Generally, signs of disease are concrete changes to the body either observed during a clinical exam or documented with clinical testing. Symptoms are how the patient experiences the disease like tiredness or soreness.
Some diseases are invisible. A person can have a disease without obvious signs and symptoms. For example, a patient may have a cancerous growth that has not caused any functional organ changes or caused any symptoms visible to others.
This is one of the reasons why clinical diagnostic tests are important. They allow healthcare providers to confirm or identify evidence of infection and/or disease, even when there are no obvious signs or symptoms. People can be colonized and infected, with microbes and remain symptom free. Patients, and sometimes doctors, struggle to determine when the presence of a microbe truly explains disease.
Drawing a line between disease and health can be complicated. In truth, the microbiome can make distinguishing this line even more complex. The human microbiome is the system of bacteria that live in your body. It is ever changing and includes good bacteria, bad bacteria, and opportunistic bacteria that act as an opportunistic microbe under certain conditions.
Check out our recent blog post on bacteria vs viruses where we explore what defines “bacteria.”
The microbiome is such an important part of our ecosystems. How much can it change and still be considered “normal”? Let’s explore this question through three bacteria: Escherichia coli, Helicobacter pylori and Bartonella henselae.
Escherichia coli
Escherichia coli are responsible for a variety of different infections, and are the most common cause of urinary tract infection. However, many strains are a normal part of the human microbiome. E. coli are one of the first bacteria to colonize an infant’s gut at birth, but by age one they are reduced to a minor player in the microbiome. The predominant E. coli strain present within the microbiome changes throughout a person’s life. Scientists experimented with selective strain reintroduction to learn more about the factors influencing strain selection within the microbiome and discovered a complex interplay between the body and the selected strains.
We are regularly exposed to E. coli strains from other people (horizontal transmission), from animals (zoonotic transmission), and from the food we eat. However, for the most part, these foreign strains move through the gut quickly without any issues because they aren’t well-adapted to live in the human gut.
If E. coli is part of a normal gut microbiome, then when can it cause harm? There are two human strains of E. coli that can cause urinary tract infection. Urinary tract infections have been heavily studied in terms of the issue of infection versus disease. While health practitioners are not unified on this topic, many would say that the presence of bacteria alone does not constitute disease, but a “urinary tract infection” is defined by an overgrowth of bacteria that harm the host by eliciting symptoms.
Some people have bacteria in their bladder but present no symptoms. The explanation for this is unknown. Some scientists hypothesize that if the strains that causes UTIs are a part of the person’s microbiome, they don’t develop the irritation that causes inflammation and pain associated with a UTI. It is further theorized that when bacteria from these strains are later encountered and aren’t present within an individual’s microbiome they cause symptoms.
Helicobacter pylori
Helicobacter pylori are bacteria that can cause peptic ulcers and, much less frequently, stomach cancer. They are also a common resident of the human gut microbiome. These opportunistic pathogens were discovered recently. In 1982, two Australian researchers discovered bacteria in an inflamed mucosa from stomach biopsies from a patient’s peptic ulcers. They identified the bacteria as H. pylori. Their finding that H. pylori caused stomach ulcers was at first vehemently rejected by the scientific community.
In a round of risky self-experimentation, Dr. Barry Marshall swallowed the bacteria and developed a severe gastric infection which resolved completely with a course of antibiotic therapy. Eventually antibiotics were recommended as a treatment for stomach and intestinal ulcers with a success rate around 90%.
H. pylori is classified as a opportunistic microbe (bad bacteria), but is it, really? Research has found that H. pylori likely has been with humans since before we even were humans. Some evidence suggests that H. pylori may be slowly dying out. When people are colonized by H. pylori it generally happens before they reach the age of 10 years old. In addition to gastric diseases, colonization with these bacteria is also associated with dysfunction of everything from bone density to stem cell division.
However, H. pylori have also been associated with health benefits like decreased asthma, eczema and other allergic disorders, and protection of the tissue of the esophagus. The presence of these bacteria may also protect people from diarrhea causing diseases and from obesity. Ultimately, most people who have H. pylori never know it’s there.
Bartonella henselae
In the Americas, Bartonella henselae is the most common Bartonella species that causes infection in people. Despite causing illnesses that can be severe leading to blindness, heart damage and more, blood donor surveys have found that apparently healthy people carry the bacteria as part of their blood microbiome. A blood donor survey in Chile found 13.6% of blood donors were PCR positive for Bartonella species. This means that researchers identified DNA evidence of the bacteria in the blood. Another study of 500 blood donors in Brazil, coauthored by Galaxy Diagnostics scientists, found 3.2% of donors had DNA evidence of infection by BAPGM enrichment and PCR (Bartonella ePCR™). This study also found that these healthy individuals with Bartonella species DNA in their blood were often not positive for antibodies against any Bartonella species.
Like H. pylori and E. coli, Bartonella species have been with humans for a very long time. Bartonella quintana was found in the tooth of a person who died 4,000 years ago and was documented in a good number of soldiers graves from Napoleon’s army. Bartonella henselae were more recently discovered in 1990 as the key agent causing cat scratch disease, skin lesions, and heart and liver complications in HIV/AIDS patients.
These highly fastidious, slow-growing opportunistic pathogens have coevolved with humans and animals over the course of history. In fact, emerging research shows that Bartonella species have developed a complex signaling relationship with the human body and are associated with a wide range of symptoms affecting multiple systems of the body.
Find out more about the technology used at Galaxy Diagnostics.
So, when IS an infection a disease?
Bacteria, even those opportunistic pathogens that lead to disease, play a complex role in our microbiomes. This makes it difficult to identify when an infection is simply colonization or the cause of disease. An E. coli strain that may be normal in one part of a person’s life may be associated with disease at a different part of their life. H. pylori may prevent allergic reactions for some but cause serious GI issues for others. Bartonella henselae is present in the bloodstream of perhaps 1 in 30 healthy, asymptomatic people with little to no immune response.
In this way, the human microbiome is highly complex and little understood. Microorganisms in and on the human body outnumber our own cells and weigh up to 6 pounds in total for the average size adult. Bacteria generate powerful metabolites that affect our mood and even how medications are processed in our body.
At the same time, most healthy people are colonized with microbes that can cause disease. They may never develop symptoms or produce antibodies. Scientists speculate that a healthy microbiome can keep these potential pathogens in check and ensure good immune function in the event of an imbalance or overgrowth. Importantly, scientists in infectious disease are moving away from the conventional “one pathogen, one disease model” to a more complex view of the role of polymicrobial infections, colonization with opportunistic pathogens. This evolves into the study of the ‘pathobiome’ as a cause of complex disease processes.
Some opportunistic infections involve hard-to-detect pathogens, like Bartonella. Illuminating the role that these pathogens play in human and animal disease is only made possible by advancing detection methods for low abundance pathogens and tailoring those diagnostic solutions to the pathobiology of the organism. This is why Galaxy Diagnostics goes beyond the limits of detection to offer direct and indirect testing methods for stealth pathogens.
References
Infection vs. Disease
Casadevall, A & Pirofski, L. (2014, December 10). Microbiology: ditch the term pathogen. Nature, 516, 165–166 (2014). https://doi.org/10.1038/516165a
National Institutes of Health. (2012, June 13). NIH Human Microbiome Project defines normal bacterial makeup of the body. https://www.nih.gov/news-events/news-releases/nih-human-microbiome-project-defines-normal-bacterial-makeup-body
E. coli
Givler, DN & Givler A. (2022, July 19). Asymptomatic bacturiuria. StatPearls https://www.ncbi.nlm.nih.gov/books/NBK441848/#:~:text=Introduction-,Asymptomatic%20bacteriuria%20is%20the%20presence%20of%20bacteria%20in%20the%20properly,the%20incidence%20increases%20with%20age.
Martinson, J.N.V. & Walk, S.T. (2020, September 29). Escherichia coli residency in the gut of healthy human adults. EcoSal Plus, 9(1):10.1128 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523338/
H. pylori
Cover, T.L. & Blaser M.J. (2009, May 7). Helicobacter pylori in health and disease. Gastroenterology, 136(6):1863-1873 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644425
Ahmed, N. (2005, October 31). 23 years of the discover of Helicobacter pylori: Is the debate over? Annals of Clinical Microbiology and Antimicrobials, 2005 Oct 31;4:17. doi: 10.1186/1476-0711-4-17 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1283743/
B. henselae
Drancourt, M. et al. (2005, February 15). Bartonella quintana in a 4000-year-old human tooth. Journal of Infectious Disease, 191(4):607-11. doi: 10.1086/427041 https://pubmed.ncbi.nlm.nih.gov/15655785/
Núñez, M.A. (2017, December). Prevalencia de Bartonella henselae endonantes de sangre y riesgo de transmisión sanguínea en Chile. Revista chilena de infectología, vol 23, no. 6 https://pubmed.ncbi.nlm.nih.gov/29488546/
Vissotto de Paiva Diniz, P.P. et al. (2016, March). Risk factors for Bartonella species infection in blood donors from southeast Brazil. PLoS Neglected Tropical Diseases, 10(3): e0004509 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801220/
Pitassi, L.H.U. et al. (2015, January 15). Bartonella spp. Bacteremia in blood donors from Campinas, Brazil. PLoS Neglected Tropical Diseases, 9(1):e0003467 https://pubmed.ncbi.nlm.nih.gov/25590435/
Raoult D. et al. (2006, January 1). Evidence for louse-transmitted diseases in soldiers of Napoleon’s Grand Army in Vilnius. Journal of Infectious Diseases, 193(1):112-20.doi: 10.1086/498534 https://pubmed.ncbi.nlm.nih.gov/16323139/
