These new insights might lead to a new line of clinical laboratory testing, particularly if the results could guide the patient to microbiome-based repellents that would remain effective for months once applied
Researchers are beginning to identify what compounds make individuals more attractive to mosquitos. That is a first step in the development of a biomarker that could be developed into a clinical laboratory test. Question is: would there be enough consumers wanting to do a lab test to determine if they were highly attractive to mosquitos, thus making this a revenue-generating test for labs?
At a minimum, there would be widespread consumer interest to at least understand why some individuals get more mosquito bites than others. What may be of particular interest to microbiologists is the statement by molecular biologist Omar Akbari, PhD, of the University of California, San Diego, who told Scientific American that by “taking human-colonizing skin bacteria … and engineering them in such a way that they can either express a repellent compound or be able to degrade something that’s attractive,” a mosquito repellant could be developed that would last for months once applied.
“This study clearly shows that these acids are important,” neurogeneticist Matthew DeGennaro, PhD (above), told CNN. “… how the mosquitoes perceive these carboxylic acids is interesting because these particular chemicals … are hard to smell at a distance. It could be that these chemicals are being altered by … the skin microbiome … if we understand why mosquitoes find a host, we can design new repellents that will block the mosquitoes from sensing those chemicals, and this could be used to improve our current repellents.” Clinical laboratory testing will be needed to produce biomarkers for developing such improved repellents. (Photo copyright: Laboratory of Tropical Genetics.)
Clinical Laboratory Testing Needed to Identify Levels of Carboxylic Acids
To complete their study, the researchers had 64 participants wear nylon stockings for six hours on their arms to get their unique scent into the fabric. The scent on the stockings was not discernible to the human nose, but it was to the mosquitos.
Two pieces of the nylon were then placed in a closed container with Aedes aegypti mosquitoes. The researchers found that certain samples were more popular with the mosquitos than others. Upon further analysis the researchers found that the most popular samples came from subjects with higher levels of carboxylic acids, and the least popular had the lowest levels. The scientists ran the test with the same participants several times over three years and the results remained largely the same.
Carboxylic acid is an organic compound found in humans in sebum, the oily layer protecting our skin. The level at which humans release carboxylic acid varies from person to person. And there is no discernible way the human nose can determine whether a person has the level of carboxylic acid on the skin that mosquitos find desirable. The answer would need to be determined by a diagnostic test performed in a clinical laboratory.
Although the development of a test to determine someone’s susceptibility to mosquitos may be far away, there could be significant consumer interest in developing such a test.
“The question of why some people are more attractive to mosquitoes than others—that’s the question that everybody asks,” Leslie B. Vosshall, PhD, Chief Scientific Officer, Howard Hughes Medical Institute, who led the research team to find out why some people are more attractive to mosquitos than others, told Scientific American. “My mother, my sister, people in the street, my colleagues—everybody wants to know.” She credits their interest as the inspiration for embarking on the study.
“Understanding what makes someone a ‘mosquito magnet’ will suggest ways to rationally design interventions such as skin microbiota manipulation to make people less attractive to mosquitoes. We propose that the ability to predict which individuals in a community are high attractors would allow for more effective deployment of resources to combat the spread of mosquito-borne pathogens,” the researchers wrote in their Cell paper.
Preventing Spread of Deadly Diseases
Although mosquitos are an annoyance, they also can be dangerous vectors of disease.
“Every bite of these mosquitoes puts people into public health danger. Aedes aegypti mosquitoes are vectors for dengue, yellow fever, and Zika,” Vosshall told CNN. “Those people who are magnets are going to be much more likely to be infected with viruses.”
Further research into these early findings may help develop diagnostic tests to protect against the spread of these diseases and identify individuals who are more attractive to the mosquitos, and therefore, more likely to contract and spread disease.
Being able to identify which individuals are mosquito magnets could help keep individuals safe from dangerous diseases, and development of a better repellent could also make outdoor summer events more bearable for the (unfortunately) popular among the pests. Medical laboratory tests associated with determining an individual’s susceptibility to mosquito bites could give clinical laboratories a new way to add value to consumers and patients.
Researchers found that early in life intestinal microorganisms “educate” the thymus to develop T cells; findings could lead to improved immune system therapeutics and associated clinical laboratory tests
The researchers published their findings in Nature. They used engineered mice as the test subjects and say the study could lead to a greater understanding of human conditions such as Type 1 and Type 2 diabetes and inflammatory bowel disease (IBD). In turn, this new knowledge could lead to new diagnostic tests for clinical laboratories.
“From the time we are born, our immune system is set up so that it can learn as much as it can to distinguish the good from the bad,” Matthew Bettini, PhD, Associate Professor of Pathology said in a University of Utah news release.
Does Gut Bacteria ‘Educate’ the Immune System?
The researchers were attempting to learn how the body develops T cells specific to intestinal microorganisms. T cells, they noted, are “educated” in the thymus, an organ in the upper chest that is key to the adaptive immune system.
“Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection,” they wrote in their study. “Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen, while limiting inflammatory anti-commensal responses.”
Findings Challenge Earlier Assumptions about Microbiota’s Influence on Immunity
The researchers began by seeding the intestines of mice with segmented filamentous bacteria (SFB), which they described as “one of the few commensal microorganisms for which a microorganism-specific T-cell receptor has been identified.” In addition, SFB-specific T cells can be tracked using a magnetic enrichment technique, they wrote in Nature.
They discovered that in young mice, microbial antigens from the intestines migrated to the thymus, resulting in an expansion of T cells specific to SFB. But they did not see an expansion of T cells in adult mice, suggesting that the process of adapting to microbiota happens early.
“Our study challenges previous assumptions that potential pathogens have no influence on immune cells that are developing in the thymus,” Bettini said in the news release. “Instead, we see that there is a window of opportunity for the thymus to learn from these bacteria. Even though these events that shape which T cells are present happen early in life, they can have a greater impact later in life.”
For example, T cells specific to microbiota can also protect against closely related harmful bacteria, the researchers found. “Mice populated with E. coli at a young age were more than six times as likely to survive a lethal dose of Salmonella later in life,” the news release noted. “The results suggest that building immunity to microbiota also builds protection against harmful bacteria the body has yet to encounter.”
According to the researchers, in addition to protecting against pathogens, “microbiota-specific T cells have pathogenic potential.” For example, “defects in these mechanisms could help explain why the immune system sometimes attacks good bacteria in the wrong place, causing the chronic inflammation that’s responsible for inflammatory bowel disease,” they suggested.
Other Clinical Laboratory Research into the Human Microbiome
All of this suggests the potential in the future “for clinical laboratories and microbiologists to do microbiome testing in support of clinical care,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report. Of course, more research is needed in these areas.
“We believe that our findings may be extended to areas of research where certain bacteria have been found to be either protective or pathogenic for other conditions, such as Type 1 and Type 2 diabetes,” Bettini said in the University of Utah news release. “Now we’re wondering, will this window of bacterial exposure and T cell development also be important in initiating these diseases?”
Following the raid, the company’s co-founders resigned
from the board of directors
Microbiome testing company, uBiome, a biotechnology developer that offers at-home direct-to-consumer (DTC) test kits to health-conscious individuals who wish to learn more about the bacteria in their gut, or who want to have their microbiome genetically sequenced, has recently come under investigation by insurance companies and state regulators that are looking into the company’s business practices.
reported that the Federal Bureau of
Investigation (FBI) raided the company’s San Francisco headquarters in
April following allegations of insurance fraud and questionable billing
practices. The alleged offenses, according to CNBC, included claims that
uBiome routinely billed patients for tests multiple times without consent.
Hospital Review wrote that, “Billing documents obtained by The Wall Street
Journal and described in a June 24 report further illustrate uBiome’s
allegedly improper billing and prescribing practices. For example, the
documents reportedly show that the startup would bill insurers for a lab test
of 12 to 25 gastrointestinal pathogens, despite the fact that its tests only
included information for about five pathogens.”
Company Insider Allegations Trigger FBI Raid
In its article, CNBC stated that “company insiders”
alleged it was “common practice” for uBiome to bill patients’ insurance
companies multiple times for the same test.
“The company also pressured its doctors to approve tests
with minimal oversight, according to insiders and internal documents seen by CNBC.
The practices were in service of an aggressive growth plan that focused on
increasing the number of billable tests served,” CNBC wrote.
FierceBiotech reported that, “According to previous
reports, the large insurers Anthem, Aetna, and Regence BlueCross BlueShield
have been examining the company’s billing practices for its physician-ordered
tests—as has the California Department of Insurance—with probes focusing on
possible financial connections between uBiome and the doctors ordering the
tests, as well as rumors of double-billing for tests using the same sample.”
Becker’s Hospital Review revealed that when the FBI
raided uBiome they seized employee computers. And that, following the raid,
uBiome had announced it would temporarily suspend clinical operations and not
release reports, process samples, or bill health insurance for their services.
The company also announced layoffs and that it would stop
selling SmartJane and SmartGut test kits, Becker’s reported.
uBiome Assumes New Leadership
Following the FBI raid, uBiome placed its co-founders Jessica
Richman (CEO) and Zac
Apte (CTO) on administrative leave while conducting an internal
investigation (both have since resigned from the company’s board of directors).
The company’s board of directors then named general counsel, John Rakow, to be interim CEO,
After serving two months as the interim CEO, Rakow resigned
from the position. The interim leadership of uBiome was then handed over to
three directors from Goldin
Associates, a New York City-based consulting firm, FierceBiotech
reported. They include:
SmartFlu: a nasal microbiome swab that detects bacteria and viruses associated with the flu, the common cold, and bacterial infections.
What Went Wrong?
Richman and Apte founded uBiome in 2012 with the intent of
marketing a new test that would prove a link between peoples’ microbiome and their
overall health. The two founders initially raised more than $100 million from
venture capitalists, and, according to PitchBook,
uBiome was last valued at around $600 million, Forbes
Nevertheless, as a company, uBiome’s future is uncertain. Of
greater concern to clinical laboratory leaders is whether at-home microbiology
self-test kits will become a viable, safe alternative to tests traditionally performed
by qualified personnel in controlled laboratory environments.
If the link between certain types of gut bacteria and improved effectiveness of certain cancer treatments can be leveraged, then medical laboratories could soon have another diagnostic tool to use in supporting physicians with cancer care
The goal of both studies was to determine whether there was a link between gut bacteria and the efficacy of cancer drugs known as PD-1 inhibitors. These drugs are used for several types of cancer, including:
They function by freeing up the immune system to attack cancer cells.
Greater Bacterial Diversity in Gut Brings Improved Response to PD-1 Inhibitors
For this study, researchers at the MD Anderson Cancer Center at the University of Texas collected oral, gut, and fecal microbiome samples and tumor biopsies from 112 patients with advanced melanoma. Clinical laboratorians took the samples before and after PD-1 treatments. They divided the patients into two groups—responders and non-responders—and profiled each microbiome using genetic sequencing.
“What we found was impressive: There were major differences both in the diversity and composition of the gut microbiome in responders versus non-responders,” Jennifer Wargo, MD, MMSc, leader of the study, told STAT. “Those who did well had greater bacterial diversity in their gut, whereas those whose tumors didn’t much shrink had fewer varieties of microbes present.”
Melanoma patients who experienced success with PD-1 therapy had a more diverse microbiome and higher concentrations of bacteria known as Ruminococcus and Faecalibacterium. Patients involved in the study who did not respond well to PD-1 therapy had the presence of another bacterium called Bacteroidales.
Jennifer Wargo, MD (above center) with her team at the MD Anderson laboratories. The researchers cautioned that clinical trials are needed before a definitive conclusion can be reached on whether altering gut bacteria can improve the effectiveness of PD-1 therapy. “If you’re changing the microbiome, depending on how you do it, it may not help you—and it might harm you,” Wargo emphasized in STAT. “Don’t try this at home.” (Photo copyright: MD Anderson.)
Antibiotics Can Reduce Effectiveness of PD-1Therapy
Researchers for this study, led by Laurence Zitvogel, MD, PhD, of the Gustave Roussy Cancer Campus in Villejuif, France, examined 249 patients who were given a PD-1 inhibitor for lung, kidney, or urinary tract cancers. A little over one fourth of these patients had recently taken antibiotics, which can strip the gut of essential bacteria necessary to treat infections.
The team found that patients who had ingested an antibiotic relapsed faster and did not live as long as patients who had not taken an antibiotic before receiving PD-1 therapy. When they analyzed variances between patients who responded well to treatment versus patients who did not, they detected the presence of Akkermansia muciniphila, a mucin-degrading bacterium, in the responders.
Personalized Treatment Based on Each Patient’s Gut Microbiome
The culmination of this type of research raises questions about how cancer medications may interact with microbiomes.
“Should we be profiling the gut microbiome in cancer patients going into immunotherapy?” asked Wargo in the STAT article. “And, should we also be limiting, or closely monitoring, the antibiotic use in these patients?
“This is all very context-specific, and multiple different factors need to be considered on how best to change the microbiome,” she continued. “When it comes to optimizing cancer therapy, treatments will have to be heavily personalized, based on what a patient’s gut microbiome looks like already.”
Diagnostic tests that could determine whether a certain drug will be beneficial for a patient would perform a critical role in healthcare decision-making. Since cancer drug treatments can cost tens of thousands of dollars or more, it would be advantageous to know which therapies would be optimal for individual patients. The hope is that in the future, clinicians, working with anatomic pathologists and clinical laboratories, will have the tools needed to ascertain if patient’s microbiomes will best work with a particular drug and if they would likely encounter any side effects.
Additional studies are needed before medical laboratory tests for ‘lean’ microbes can be developed for use by physicians treating overweight and obese patients
Researchers at Cornell University have identified a family of microbes that may provide a genetic explanation for why some people are able to stay thin. If their findings are validated, a clinical laboratory test for these bacteria, and a macrobotic regiment to help people lose weight or stay lean, could be down the road.
Ruth Ley, Ph.D., is a Cornell University Associate Professor of Microbiology, and the research paper’s senior author. She believes the new Cornell study makes clear the connection between the human genotype and health-associated gut bacteria. (more…)