Clinical laboratory scientists and microbiologists could play a role in helping doctors explain to patients the potential dangers of do-it-yourself medical treatments
Be careful what you wish for when you perform do-it-yourself (DIY) medical treatments. That’s the lesson learned by a woman who was seeking relief for irritable bowel syndrome (IBS). When college student Daniell Koepke did her own fecal transplant using poop from her brother and her boyfriend as donors her IBS symptoms improved, but she began to experience medical conditions that afflicted both fecal donors.
“It’s possible that the bacteria in the stool can influence inflammation in the recipient’s body, by affecting their metabolism and activating their immune response,” microbial ecologist Jack Gilbert, PhD, Professor and Associate Vice Chancellor at University of California San Diego (UC San Diego) told Business Insider. “This would cause shifts in their hormonal activity, which could promote the bacteria that can cause acne on the skin. We nearly all have this bacterium on skin, but it is often dormant,” he added.
A Fecal Microbiota Transplant (FMT) is a procedure where stool from a healthy donor is transplanted into the microbiome of a patient plagued by a certain medical condition.
Our guts are home to trillions of microorganisms (aka, microbes), known as the gut microbiota, that serve many important functions in the body. The microbiome is a delicate ecosystem which can be pushed out of balance when advantageous microbes are outnumbered by unfavorable ones. An FMT is an uncomplicated and powerful method of repopulating the microbiome with beneficial microbes.
“With fecal microbiome transplants there is really compelling evidence, but the science is still developing. We’re still working on if it actually has benefits for wider populations and if the benefit is long-lasting,” said Gilbert in a Netflix documentary titled, “Hack Your Health: The Secrets of Your Gut.”
“The microbial community inside our gut can have surprising influences on different parts of our body,” microbial ecologist Jack Gilbert, PhD (above), of the Gilbert Lab at University of California San Diego told Business Insider. “Stools are screened before clinical FMTs, and anything that could cause major problems, such as certain pathogens, would be detected. When you do this at home, you don’t get that kind of screening.” Doctors and clinical laboratories screening patients for IBS understand the dangers of DIY medical treatments. (Photo copyright: University of California San Diego.)
Changing Poop Donors
When Koepke began experiencing symptoms of IBS including indigestion, stabbing pains from trapped gas and severe constipation, she initially turned to physicians for help.
In the Netflix documentary, Koepke stated that she was being prescribed antibiotics “like candy.” Over the course of five years, she completed six rounds of antibiotics per year, but to no avail.
She also changed her diet, removing foods that were making her symptoms worse. This caused her to lose weight and she eventually reached a point where she could only eat 10 to 15 foods.
“It’s really hard for me to remember what it was like to eat food before it became associated with anxiety and pain and discomfort,” she said.
In an attempt to relieve her IBS symptoms, Koepke made her own homemade fecal transplant pills using donated stool from her brother. After taking them her IBS symptoms subsided and she slowly gained weight. But she developed hormonal acne just like her brother.
Koepke then changed donors, using her boyfriend’s poop to make new fecal transplant pills. After she took the new pills, her acne dissipated but she developed depression, just like her boyfriend.
“Over time, I realized my depression was worse than it’s ever been in my life,” Koepke stated in the documentary.
She believes the microbes that were contributing to her boyfriend’s depression were also transplanted into her via the fecal transplant pills. When she reverted to using her brother’s poop, her depression abated within a week.
Gilbert told Business Insider his research illustrates that people who suffer from depression are lacking certain bacteria in their gut microbiome.
“She may have had the ‘anti-depressant’ bacteria in her gut, but when she swapped her microbiome with his, her anti-depressant bacteria got wiped out,” he said.
FDA Approves FMT Therapy for Certain Conditions
Typically, the fecal material for an FMT procedure performed by a doctor comes from fecal donors who have been rigorously screened for infections and diseases. The donations are mixed with a sterile saline solution and filtered which produces a liquid solution. That solution is then administered to a recipient or frozen for later use.
On November 30, 2022, the US Food and Drug Administration (FDA) approved the first FMT therapy, called Rebyota, for the prevention of Clostridioides difficile (C. diff.) in adults whose symptoms do not respond to antibiotic therapies. Rebyota is a single-dose treatment that is administered rectally into the gut microbiome at a doctor’s office.
Then, in April of 2023, the FDA approved the use of a medicine called Vowst, which is the first oral FMT approved by the FDA.
According to the Cleveland Clinic, scientists are exploring the possibility that fecal transplants may be used as a possible treatment for many health conditions, including:
Doctors and clinical laboratories know that do-it-yourself medicine is typically not a good idea for obvious reasons. Patients seldom appreciate all the implications of the symptoms of an illness, nor do they fully understand the potentially dangerous consequences of self-treatment. Scientists are still researching the benefits of fecal microbiota transplants and hope to discover more uses for this treatment.
Phages are miniscule, tripod-looking viruses that are genetically programmed to locate, attack, and eradicate a specific kind of pathogen. These microscopic creatures have saved lives and are being touted as a potential solution to superbugs, which are strains of bacteria, viruses, parasites, and fungi that are resistant to most antibiotics and other treatments utilized to counteract infections.
“These multi-drug-resistant superbugs can cause chronic infections in individuals for months to years to sometimes decades,” Dwayne Roach, PhD, Assistant Professor of Bacteriophages, Infectious Disease, and Immunology at SDSU told CNN. “It’s ridiculous just how virulent some of these bacteria get over time.”
Labs across the country are conducting research on phages in eradicating superbugs. Roach’s lab is currently probing the body’s immune response to phages and developing purification techniques to prepare phage samples for intravenous use in patients.
“There are a lot of approaches right now that are happening in parallel,” said Dwayne Roach, PhD (above), Assistant Professor of Bacteriophages, Infectious Disease, and Immunology at San Diego State University (SDSU), in a CNN interview. “Do we engineer phages? Do we make a phage cocktail, and then how big is the cocktail? Is it two phages or 12 phages? Should phages be inhaled, applied topically, or injected intravenously? There’s a lot of work underway on exactly how to best do this.” Clinical laboratories that test for bacterial infections may play a key role in diagnosis and treatment involving bacteriophages. (Photo copyright: San Diego State University.)
Building Libraries of Phages
When certain a bacterial species or its genotypes needs to be annihilated, a collection of phages can be created to attack it via methods that enter and weaken the bacterial cell. The bacteria will attempt to counter the intrusion by employing evasive actions, such as shedding outer skins to eliminate the docking ports utilized by the phages. These maneuvers can cause the bacteria to lose their antibiotic resistance, making them vulnerable to destruction.
Some research labs are developing libraries of phages, accumulating strains found in nature in prime breeding grounds for bacteria to locate the correct phage for a particular infection. Other labs, however, are speeding up the process by producing phages in the lab.
“Rather than just sourcing new phages from the environment, we have a bioreactor that in real time creates billions upon billions of phages,” Anthony Maresso, PhD, Associate Professor at Baylor College of Medicine in Houston told CNN. “Most of those phages won’t be active against the drug-resistant bacteria, but at some point, there will be a rare variant that has been trained, so to speak, to attack the resistant bacteria, and we’ll add that to our arsenal. It’s a next-generation approach on phage libraries.”
For the Baylor study, 12 patients were treated with phages customized to each individual’s unique bacterial profile. The antibiotic-resistant bacteria were exterminated in five of the patients, while several others showed improvement.
Clinical trials are currently being executed to test the effectiveness of phages against a variety of chronic health conditions, including:
Using a phage cocktail could be used to treat a superbug outbreak in real time, while preventing a patient from a future infection of the same superbug.
“The issue is that when patients have infections with these drug-resistant bacteria, they can still carry that organism in or on their bodies even after treatment,” Maroya Walters, PhD, epidemiologist at the federal Centers for Disease Control and Prevention (CDC) told CNN.
“They don’t show any signs or symptoms of illness, but they can get infections again, and they can also transmit the bacteria to other people,” she added.
The colorized transmission electron micrograph above shows numerous phages attached to a bacterial cell wall. Phages are known for their unique structures, which resemble a cross between NASA’s Apollo lunar lander and an arthropod. (Caption and photo copyright: Berkeley Lab.)
More Studies are Needed
According to CDC data, more than 2.8 million antimicrobial-resistant (AMR) infections occur annually in the United States. More than 35,000 people in the country will die as a result of these infections.
In addition, AMR infections are a huge global threat, associated with nearly five million deaths worldwide in 2019. Resistant infections can be extremely difficult and sometimes impossible to treat.
More research is needed before phages can be used clinically to treat superbugs. But if phages prove to be useful in fighting antibiotic-resistant bacteria, microbiologists and their clinical laboratories may soon have new tools to help protect patients from these deadly pathogens.
In a separate study, HHS finds a 40% increase in sepsis cases, as more patients succumb to infections without effective antibiotics and antimicrobial drugs
Given the drastic steps being taken to slow the spread of the Coronavirus in America, it’s easy to forget that significant numbers of patients die each year due to antibiotic-resistant bacteria (ARB), other forms of antimicrobial resistance (AMR), and in thousands of cases the sepsis that follows the infections.
The CDC’s website states that “more than 2.8 million antibiotic-resistant infections occur in the US each year, and more than 35,000 people die as a result.” And a CDC news release states, “on average, someone in the United States gets an antibiotic-resistant infection every 11 seconds and every 15 minutes someone dies.”
Those are huge numbers.
Clinical laboratory leaders and microbiologists have learned to be vigilant as it relates to dangerously infectious antimicrobial-resistant agents that can result in severe patient harm and death. Therefore, new threats identified in the CDC’s Antibiotic Resistance Threats in the United States report will be of interest.
Drug-resistant Microbes That Pose Severe Risk
The CDC has added the fungus Candida auris (C. auris) and carbapenem-resistant Acinetobacter (a bacteria that can survive for a long time on surfaces) to its list of “urgent threats” to public health, CDC said in the news release. These drug-resistant microbes are among 18 bacteria and fungi posing a greater threat to patients’ health than CDC previously estimated, Live Science reported.
In 2013, the CDC estimated that about two million people each year acquired an antibiotic-resistant (AR) infection that killed as many as 23,000. However, in 2019, the CDC reported that those numbers were low and that the number of deaths due to AR infections in 2013 was about twice that amount. During a news conference following the CDC announcement, Michael Craig (above), a Senior Adviser for the CDC’s Antibiotic Resistance Coordination and Strategy Unit said, “We knew and said [in 2013] that our estimate was conservative … and we were right,” Live Science reported. In 2019, CDC reported 2.8 million antibiotic-resistant infections annually with more than 35,000 related deaths in the US alone. (Photo copyright: Centers for Disease Control and Prevention.)
The CDC considers five threats to be urgent. Including the
latest additions, they are:
Dark Daily has regularly covered the healthcare industry’s ongoing struggle with deadly fungus and bacteria that are responsible for hospital-acquired infections (HAI) and sepsis. This latest CDC report suggests healthcare providers continue to struggle with antimicrobial-resistant agents.
Acinetobacter Threat Increases and C. auris
a New Threat since 2013
Carbapenem-resistant Acinetobacter, a bacterium that
causes pneumonia and bloodstream and urinary tract infections, escalated from
serious to urgent in 2013. About 8,500 infections and 700 deaths were noted by the
CDC in 2017.
C. auris, however, was not addressed in the 2013
report at all. “It’s a pathogen that we didn’t even know about when we wrote
our last report in 2013, and since then it’s circumvented the globe,” said Michael
Craig, Senior Adviser for the CDC’s Antibiotic Resistance Coordination and
Strategy Unit, during a news conference following the CDC announcement, Live
Science reported.
Today, C. auris is better understood. The fungus
resists emerging drugs, can result in severe infections, and can be transmitted
between patients, CDC noted.
By year-end, CDC tracking showed 988 cases in the US.
More Patients Getting Sepsis as Antibiotics Fail: HHS
Study
In a separate study published in Critical Care Medicine, a journal of the Society of Critical Care Medicine (SCCM), the US Department of Health and Human Services (HHS) found that antibiotic-resistant bacteria and fungi are resulting in more people acquiring sepsis, a life-threatening condition, according to an HHS news release.
Sepsis increased by 40% among hospitalized Medicare patients
from 2012 through 2018, HHS reported.
“These (untreatable infections) are happening here and now in the United States in large numbers. This is isn’t some developing world thing. This isn’t a threat for 2050. It’s a threat for here and now,” Cornelius “Neil” Clancy, MD, Associate Chief of Veterans Affairs Pittsburg Health System (VAPHS) and Opportunistic Pathogens, told STAT.
It is troubling to see data about so many patient deaths
related to antibiotic-resistant infections and sepsis cases when the world is
transfixed by the Coronavirus. Nevertheless, it’s important that medical laboratory
leaders and microbiologists keep track of how the US healthcare system is or is
not responding to these new infectious agents. And, to contact infection
control and environmental services colleagues to enhance surveillance, ensure
safe healthcare environments and equipment, and adopt appropriate strategies to
prevent antibiotic-resistant infections.
The UE study sheds light on the types of bacteria in
wastewater that goes down hospital pipes to sewage treatment plants. The study
also revealed that not all infectious agents are killed after passing through
waste treatment plants. Some bacteria with antimicrobial (or antibiotic)
resistance survive to enter local food sources.
The scientists concluded that the amount of AMR genes found
in hospital wastewater was linked to patients’ length-of-stays and consumption
of antimicrobial resistant bacteria while in the hospital.
In a paper the University of Edinburgh published on medRxiv, the researchers wrote: “There was a higher abundance of antimicrobial-resistance genes in the hospital wastewater samples when compared to Seafield community sewage works … Sewage treatment does not completely eradicate antimicrobial-resistance genes and thus antimicrobial-resistance genes can enter the food chain through water and the use of [processed] sewage sludge in agriculture. As hospital wastewater contains inpatient bodily waste, we hypothesized that it could be used as a representation of inpatient community carriage of antimicrobial resistance and as such may be a useful surveillance tool.”
Additionally, they wrote, “Using metagenomics to identify
the full range of AMR genes in hospital wastewater could represent a useful
surveillance tool to monitor hospital AMR gene outflow and guide environmental
policy on AMR.”
Antimicrobial stewardship programs are becoming increasingly critical to preventing the spread of AMR bacteria. “By having those programs, [there are] documented cases of decreased antibiotic resistance within organisms causing these infections,” Paul Fey, PhD, of the University of Nebraska Medical Center, told MedPage Today. “This is another indicator of how all hospitals need to implement stewardship programs to have a good handle on decreasing antibiotic use.” [Photo copyright: University of Nebraska.]
Don’t Waste the Wastewater
Antibiotic resistance occurs when bacteria change in response to medications to prevent and treat bacterial infections, according to a World Health Organization (WHO) fact sheet. The CDC estimates that more than 23,000 people die annually from two million antibiotic-resistance infections.
Wastewater, the UE scientists suggest, should not go to
waste. It could be leveraged to improve hospitals’ detection of patients with antimicrobial
resistance, as well as to boost environment antimicrobial-resistance polices.
They used metagenomics (the study of genetic material
relative to environmental samples) to compare the antimicrobial-resistance
genes in hospital wastewater against wastewater from community sewage
points.
The UE researchers:
First collected samples over a 24-hour period from various areas in a tertiary hospital;
They then obtained community sewage samples from various locations around Seafield, Scotland;
Antimicrobial-resistance genes increased with longer length of patient stays, which “likely reflects transmission amongst hospital inpatients,” researchers noted.
Fey suggests that further research into using sequencing
technology to monitor patients is warranted.
“I think that monitoring each patient and sequencing their
bowel flora is more likely where we’ll be able to see if there’s a significant
carriage of antibiotic-resistant organisms,” Fey told MedPage Today. “In
five years or so, sequencing could become so cheap that we could monitor every
patient like that.”
Fey was not involved in the University of Edinburgh
research.
Given the rate at which AMR bacteria spreads, finding antibiotic-resistance
genes in hospital wastewater may not be all that surprising. Still, the University
of Edinburgh study could lead to cost-effective ways to test the genes of
bacteria, which then could enable researchers to explore different sources of
infection and determine how bacteria move through the environment.
And, perhaps most important, the study suggests clinical
laboratories have many opportunities to help eliminate infections and slow
antibiotic resistance. Microbiologists can help move their organizations forward
too, along with infection control colleagues.
