Aug 13, 2018 | Laboratory Management and Operations, Laboratory News, Laboratory Pathology, Laboratory Testing
Without the beneficial bacteria, infants can develop gut dysbiosis, which can lead to severe chronic diseases
Another key insight into how the human microbiome performs essential functions has been discovered by a research team at the University of California, Davis (UCD). They have learned that nearly all babies born in developed nations no longer have a specific strain of bacteria called B. infantis, which digests a certain type of sugar found in breast milk.
Microbiologists, clinical laboratory scientist, and pathologists will find the UCD researcher’s discovery to be a fascinating insight into a newly-understood function of the human microbiome. Assuming that further research confirms these early findings, it also could lead to a medical laboratory assay for use during pregnancy or after delivery that would enable physicians to determine if the newborn is missing this strain of bacteria and what therapies would be appropriate.
Babies in Developed Nations Lack Beneficial B. infantis Bacteria
“The central benefits of having a microbiota dominated by B. infantis is that it crowds all the other guys out—especially pathogenic bacteria, which can cause both acute illnesses and chronic inflammation that leads to disease,” UC Davis researcher Bruce German, PhD, Professor and Chemist, Food Science and Technology, told the New York Times.
The UC Davis researchers published their study findings in mSphere, a journal of the American Society for Microbiology. In their paper they note that Bifidobacterium Infantis or B. infantis, a beneficial bacteria that aids in digestion, is missing from the microbiomes of infants in developed nations, such as the United States.
The study hypothesized that the reduction and eventual absence of B. infantis in American babies was the consequence of three factors:
- An increase in cesarean births;
- Use of commercial formulas instead of breast milk; and,
- Heightened use of antibiotics.
According to the New York Times, “Dr. German and his colleagues learned about the missing bacterium by studying breast milk. They found that the milk contains an abundance of oligosaccharides, carbohydrates that babies are incapable of digesting. Why would they be there if babies can’t digest them? They realized that these carbohydrates weren’t feeding the baby—they were feeding B. infantis.”
Good versus Bad Gut Bacteria
Because 70-80% of our immune system resides within our gastrointestinal tract, gut bacteria play an important role in our overall health. Breast milk contains essential probiotics and anti-inflammatory compounds that help “friendly” bacteria flourish in the infant gut.
There are more than two hundred different sugars or carbohydrates found in breast milk, known as human milk oligosaccharides (HMOs). They are one of the most copious components in breast milk but are completely indigestible by humans. So, why are they there?
Because they serve a critical role as food for microbes or prebiotics. Scientists have discovered that HMOs present in breast milk are there to feed the B. infantis, not to nourish the baby.
HMOs also act as a decoy to confuse undesirable bacteria from doing damage in the gut.
“Bad” bacteria are inclined to latch onto sugar molecules in intestinal cells. Because HMOs are very similar to those sugar molecules, the undesirable bacteria will instead latch onto the HMOs in a baby’s gut and leave vulnerable intestinal cells alone.
The primary benefits of B. infantis include:
- Production of short-chain fatty acids. When infantis digests HMOs, some short-chain fatty acids are released, which provide energy and help control yeast and fungus growth.
- Support for gut integrity. infantis signals gut cells in infants to generate proteins that fill gaps between intestinal cells. These gaps can be dangerous as they may allow toxins and bad bacteria to get into the bloodstream.
- Keeping undesirable bacteria at bay. infantis consumes HMOs and usurps space in the gut so potentially dangerous bacteria cannot take up residence or cause problems.
- Release of sialic acid. As it devours HMOs, infantis churns and releases sialic acid, a crucial nutrient for the brain development of infants.
- Production of folate. infantis also produces folate, which is necessary for infant development and growth and the creation of red blood cells.
“The need for clinicians to have a quick and reliable method to determine Bifidobacterium levels in [a] baby’s gut, and an effective way to replace the right Bifidobacterium to correct dysbiosis when detected, are the critical next steps for infant health,” noted Jennifer Smilowitz, PhD (above), Associate Director of Human Studies Research Program for the Foods for Health Institute at UC Davis, and one of the study authors, in a news release. (Photo copyright: UC Davis.)
The UC Davis study is the latest example of new insights about the microbiome, which refers to the collected genetic material of human microbiota. This promising field of research is expected to lead to a better understanding of how human gut bacteria affects resistance to certain chronic diseases, such as cancer, and to new clinical laboratory treatments and drug therapies.
Different research initiatives involving the human microbiome continue to indicate that gut bacteria can be a source of useful biomarkers for improving the health of individuals. Dark Daily has covered the study of human microbiome and development of new cancer therapies based on that research for many years.
Microbiome research, however, sometimes uncovers negative findings as well.
Lack of B. infantis, a principle gut microbe, can contribute to gut dysbiosis, which has been linked to chronic health conditions such as:
Researchers observed that reduction in B. infantis in the infant gut also has resulted in a rise in the pH of infant fecal matter. An analysis of 14 clinical studies performed between 1926 and 2017 showed a startling increase of pH from 5.0 to 6.5 in infant stools.
“These alarming changes to the infant gut microbiome and thus, gut environment, may be due to modern medical practices like antibiotics, C-sections, and formula feeding,” Jennifer Smilowitz, PhD, Associate Director of Human Studies Research Program for the Foods for Health Institute at UC Davis, and one of the study authors, noted in a news release. “These are all potentially life-saving medical practices but have unintended consequences on the infant gut microbiome. As a result, certain pathogenic bacteria—those linked to higher risk of health issues, such as colic, eczema, allergies, diabetes, and obesity—thrive.”
The process by which the researchers in this study identified the missing bacteria illustrates how more refined ways to examine molecules in the body are providing streamlined tools to identify elements within the body and their interaction with each other.
This new insight is one more confirmation that the human microbiome will be the source of useful diagnostic biomarkers, associated with medical laboratory therapies that can improve the health of individual patients.
—JP Schlingman
Related Information:
Elevated Fecal pH Indicates a Profound Change in the Breastfed Infant Gut Microbiome Due to Reduction of Bifidobacterium over the Past Century
The Bacteria Babies Need
Bifidobacterium Longum Subspecies Infantis: Champion Colonizer of the Infant Gut
Evolve BioSystems’ Activated B. infantis EVC001 Demonstrates Substantial and Persistent Remodeling of the Infant Gut Microbiome
How Baby’s First Microbes Could be Crucial to Future Health
Breast Milk and B. Infantis: Nature’s Favorite Probiotic
New Study Shows Significant Changes to Infant Fecal pH Over Last 100 Years
Researchers Discover Link between Gut Bacteria and the Effectiveness of Certain Cancer Drugs; Knowledge May Lead to New Types of Clinical Laboratory Tests
Researchers in Two Separate Studies Discover Gut Microbiome Can Affect Efficacy of Certain Cancer Drugs; Will Findings Lead to a New Clinical Laboratory Test?
Microbiologists at Weill Cornell Use Next-Generation Gene Sequencing to Map the Microbiome of New York City Subways
Jan 8, 2018 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Pathology, Laboratory Testing
Microbiome is once again leading scientists toward a new understanding of how human gut bacteria can impact the efficacy and side-effects of certain cancer therapies
Anatomic pathology researchers already know that a person’s genetics can affect the results of cancer treatments. Now it is becoming clear that a patient’s microbiome—which includes gut bacteria—may also impact the efficacy of particular cancer treatments. A recent study showed that gut bacteria can be used to determine whether a cancer drug will work for a certain individual and also if the patient might suffer side effects from certain cancer treatments.
Working with this knowledge, diagnostic test companies may possibly develop new clinical laboratory tests designed to help physicians better diagnose and treat cancer patients. This, in turn, advances personalized medicine and treatments for chronic diseases tailored to patients’ specific physiologies and conditions. This is a healthcare trend where medical laboratories can expect to play a critical role.
Gut Bacteria as Important as Genetics in Cancer Treatments
A recent article published in the journal Nature: npj Biofilms and Microbiomes, outlined a correlation between gut bacteria and side effects of irinotecan (sold as Camptosar), a drug used to treat metastatic colorectal cancer.
Libusha Kelly, PhD, Assistant Professor in the Departments of Systems and Computational Biology, and Microbiology and Immunology, led researchers from the Albert Einstein College of Medicine located in Bronx, N.Y., in conducting the study.
“We’ve known for some time that people’s genetic makeup can affect how they respond to a medication,” noted Kelly in an Einstein news release. “Now, it’s becoming clear that variations in one’s gut microbiome—the population of bacteria and other microbes that live in the digestive tract—can also influence the effects of treatment.”
Irinotecan is administered intravenously to colorectal cancer patients in an inactive form and is metabolized to an active form by liver enzymes. The drug is later converted back to an inactive form by other liver enzymes and the addition of a Glucuronidase chemical group. The irinotecan then enters the intestine for expulsion by the body.
Taken from the Einstein College of Medicine published study, the graph above illustrates “Two distinct metabolizer phenotypes or ‘metabotypes’ based on % SN-38 formation during a time course incubation of SN-38G with fecal samples from 20 individuals quantified by LC-MS/MS. Participants were sub-grouped into low (n = 16) and high (n = 4) metabolizer phenotypes. All samples were run in triplicate and values are the mean ± sem.” (Graphic copyright: Nature/Albert Einstein College of Medicine.)
However, bacteria residing in the digestive tract of some individuals prevent the medication from metabolizing properly and reactivates the medication, which transforms the irinotecan into a toxic substance that can cause side effects.
To perform the research, Kelly and her team collected fecal samples from 20 healthy individuals and treated those samples with inactive irinotecan. The samples were then examined and categorized by whether or not they were able to metabolize or reactivate the drug.
Identifying Potential for Side Effects in Patients a Powerful Tool for Medical Laboratories
Irinotecan can cause severe diarrhea and dehydration in up to 40% of patients who take the medication. By focusing on the presence of beta-glucuronidase (enzymes that are used to catalyze the breakdown of complex carbohydrates) the researchers found that gut bacteria can also be used to distinguish which patients will encounter side effects from the drug.
“As you can imagine, such patients are already quite ill, so giving them a treatment that causes intestinal problems can be very dangerous,” said Kelly in the news release. “At the same time, irinotecan is an important weapon against this type of cancer.”
Four of the 20 subjects in the study were determined to be high metabolizers. Due to differences in the composition of their microbiomes, the team concluded that the high metabolizers were more likely to experience side effects from irinotecan.
The research also demonstrated that beta-glucuronidase enzymes in the gut may adversely interact with some commonplace drugs, such as ibuprofen and other nonsteroidal anti-inflammatory medications (NSAIDs), morphine, and Tamoxifen, a drug that is prescribed mainly to breast cancer patients.
“In these cases, the issue for patients may not be diarrhea,” states Kelly in the news release. “Instead, if gut bacteria reactivate those drugs, then patients might be exposed to higher-than-intended doses. Our study provides a broad framework for understanding such drug-microbiome interactions.”
Microbiome Takes Center Stage in Pathology Research
As Dark Daily previously reported, from extending life to developing more powerful treatments for chronic diseases, the human microbiome is quickly becoming an important subject of research studies. The findings from such studies will trigger advances in precision medicine. And, the clinical laboratory assays developed from this research will give physicians the knowledge needed to select the most appropriate drug therapies and treatments for individual patients.
—JP Schlingman
Related Information:
Gut Bacteria Can Stop Cancer Drugs from Working
Gut Microbiome May Make Chemo Drug Toxic to Patients
Human Microbiome Signatures of Differential Colorectal Cancer Drug Metabolism
Researchers in Two Separate Studies Discover Gut Microbiome Can Affect Efficacy of Certain Cancer Drugs; Will Findings Lead to a New Clinical Laboratory Test?
Attention Microbiologists and Medical Laboratory Scientists: New Research Suggests an Organism’s Microbiome Might Be a Factor in Longer, More Active Lives
Mayo Clinic and Whole Biome Announce Collaboration to Research the Role of the Human Microbiome in Women’s Diseases Using Unique Medical Laboratory Tests
Dec 29, 2017 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory News, Laboratory Pathology, Laboratory Testing
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
From improving treatments for chronic diseases to extending lives, gut microbiome (bacteria that is part of human microbiota) has been at the forefront of developing clinical laboratory testing and anatomic pathology diagnostic technologies in recent years. Now, two studies recently published in the online journal Science confirm research that the “composition” of gut bacteria may have a significant influence on the effectiveness of certain cancer drugs.
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:
- Melanoma;
- Lung;
- Bladder; and,
- Stomach cancers.
They function by freeing up the immune system to attack cancer cells.
Greater Bacterial Diversity in Gut Brings Improved Response to PD-1 Inhibitors
One of the studies, “Gut Microbiome Modulates Response to Anti–PD-1 Immunotherapy in Melanoma Patients,” found that a microbiome populated with “good” bacteria can elevate the potency of certain drug treatments. The researchers discovered that the gut bacteria in patients who responded well to PD-1 inhibitors differed from that found in patients who did not respond to the treatment.
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
The other study, “Gut Microbiome Influences Efficacy of PD-1-based Immunotherapy Against Epithelial Tumors,” discovered that some drug therapies were less effective in patients who were also taking antibiotics to treat infections shortly before beginning treatment with PD-1 drugs.
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.
—JP Schlingman
Related Information:
Patients’ Gut Bugs May Play Role in Cancer Care
Gut Microbiome Modulates Response to Anti–PD-1 Immunotherapy in Melanoma Patients
Gut Microbiome Influences Efficacy Of PD-1–Based Immunotherapy Against Epithelial Tumors
Your Gut Bacteria Could Determine How You Respond to Cutting-edge Cancer Drugs
The Bacteria in Your Gut Could Help Determine if a Cancer Therapy Will Work
Attention Microbiologists and Medical Laboratory Scientists: New Research Suggests an Organism’s Microbiome Might Be a Factor in Longer, More Active Lives
Get the Poop on Organisms Living in Your Gut with a New Consumer Laboratory Test Offered by American Gut and uBiome
Mayo Clinic and Whole Biome Announce Collaboration to Research the Role of the Human Microbiome in Women’s Diseases Using Unique Medical Laboratory Tests
