Tag: 9/12/21

Categories : GastrointestinalTags :

Commonly Used Drugs Have a Significant Impact on Gut Microbiome

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Many commonly used drugs have powerful effects on the human gut microbiome, according to a large cohort study published in the journal Nature. These include drugs used to treat cardiometabolic disorders and antibiotics.

The human microbiome is composed of microbes that reside in and on our bodies, which have tremendous potential to impact our physiology, both in health and in disease. They contribute metabolic functions, protect against pathogens, educate the immune system, and, through these basic functions, affect directly or indirectly most of our physiologic functions.

“We analysed the effects of 28 different drugs and several drug combinations,” explained Professor Peer Bork, Director of Scientific Activities at EMBL Heidelberg, “Many drugs negatively impact the composition and state of the gut bacteria, but others, including aspirin, can have a positive influence on the gut microbiome. We found that drugs can have a more pronounced effect on the host microbiome than disease, diet, and smoking combined.”

While the negative and lasting impact of antibiotics on gut bacteria is already well-known, this study showed that such effects likely accumulate over time. “We found that the gut microbiome of patients taking multiple courses of antibiotics over five years became less healthy. That included signs indicating antimicrobial resistance,” said co-first author of the study Dr Sofia Forslund.

“We wanted to disentangle the effect that diseases have on host microbiomes from the effect of medications, particularly in patients taking more than one drug at the same time,” said co-first author Dr Maria Zimmermann-Kogadeeva. “Being part of the MetaCardis consortium enabled us to use multi-omics data from more than 2000 patients with cardiometabolic diseases,” she added. The cohort’s large size also let the researchers establish that drug dosage also has a significant effect on the level of impact on the microbiome.

“We know that the microbiome can reflect the status of a patient’s health and provide a range of biomarkers to assess the severity of diseases. What is often overlooked, however, is that the medication used to treat a disease also affects the state of the microbiome,” added Dr Rima Chakaroun, one of the lead authors.

The researchers came up with a statistical approach to tease out the effects of drugs and disease separately. “We now have a robust methodological framework that makes it possible to get rid of many of the standard errors,” said Professor Bork. “That allowed us to show that medication can mask the signatures of disease and conceal potential biomarkers or therapeutic targets.”

It is hoped that these results could potentially inform drug repurposing as well as in planning individualised treatment and prevention strategies.

The study combined the insight, knowledge and approaches of experts in six countries. “It was very motivating to work with an interdisciplinary team of clinicians, bioinformaticians, and computational systems biologists to advance our understanding of molecular interactions in cardiometabolic disease,” said Dr Zimmermann-Kogadeeva.

Source: European Molecular Biology Lab

Categories : Obstetrics & GynaecologyTags :

Thyroid Conditions may Affect Egg Reserves in Ovaries

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In an analysis published in Reproductive Medicine and Biology, researchers found evidence that thyroid conditions in women could negatively impact egg reserves in their ovaries.

Hypothyroidism is a disease that is prevalent in women, even in those of reproductive age. Thyroid hormones are involved in the control of the menstrual cycle. Oocytes express cell surface receptors for thyroid hormones that affect the actions of follicle-stimulating hormone and luteinising hormone through steroid biosynthesis. As such, thyroid dysfunction disturbs menstrual regularity and ovulation. However, the effects of low thyroid hormone levels (hypothyroidism) and thyroid autoimmune diseases on the functioning of a woman’s ovaries are not fully understood. This analysis aimed to investigate whether hypothyroidism and/or thyroid autoimmunity  affect the ovarian reserve, evaluated using levels of anti-Mullerian hormone (AMH).

The researchers found nine relevant trials, and their findings indicated that hypothyroidism and thyroid autoimmunity can negatively impact a woman’s ovarian reserve, or the total number of healthy immature eggs in the ovaries.

“Our age-stratified analysis demonstrated that thyroid autoimmunity and hypothyroidism possibly have different impacts on the ovarian reserve. It provides an important clue in determining how these conditions affect the development of ovarian follicles,” said senior author Akira Iwase, MD, PhD, of the Gunma University Graduate School of Medicine, in Japan.

Source: Wiley

Categories : COVIDTags :

New BA.2 ‘Stealth’ Omicron Variant Discovered

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Scientists have reported identifying a ‘stealth’ version of Omicron that cannot be distinguished from other variants based on standard PCR tests.

The so-called stealth variant has a number of mutations in common with standard Omicron, but it lacks the key genetic change that makes it stand out in PCR tests. This means probable cases are not flagged by routine PCR tests, even though genomic testing can identify it as the Omicron variant.

This distinctive marker had been one of the fortunate features of the new variant, as Tulio de Oliveira, director of the Centre for Epidemic Response and Innovation in South Africa, had explained: “We can detect [Omicron] very quickly, and this will help us to track and understand the spread.”

It is still too early to know whether the new form of Omicron will spread in the same way as the standard Omicron variant, researchers say. However the ‘stealth’ version is genetically distinct and so may behave differently.

The stealth variant was first spotted among recently submitted COVID virus genomes from South Africa, Australia and Canada, but it may already have spread more widely. So far it has been detected in seven individuals.

As a result of this new variant, researchers have split the B.1.1.529 lineage into standard Omicron (BA.1) and the newer variant (BA.2).

“There are two lineages within Omicron, BA.1 and BA.2, that are quite differentiated genetically,” said Professor Francois Balloux, director of the University College London Genetics Institute. “The two lineages may behave differently.”

Whole genome analysis confirms which variant has caused a COVID infection, but PCR tests can sometimes give an indication. About half of the UK’s PCR machines search for three genes in the virus, but Omicron only tests positive for two. This is because Omicron has a deletion in the “S” or spike gene, similar to Alpha before it. This glitch means PCR tests displaying so-called “S gene target failure” strongly suggest Omicron infection.

Informally, some researchers are calling the new variant “stealth Omicron” because it lacks the deletion that allows PCR tests to spot it.

One major unknown is how the new variant emerged. While it falls under Omicron, it is so genetically distinct that it may qualify as a new “variant of concern” if it spreads rapidly. Having two variants arise in quick succession with shared mutations is “worrying” according to one researcher, and suggests public health surveillance “is missing a big piece of the puzzle”.

Source: The Guardian

Categories : Medical Research & TechnologyTags :

US Army Scientists Develop Novel Anthrax Treatment

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Capsule removal from Bacillus anthracis by treatment with Capsule Depolymerase (capsule shown in red). Credit: Photomicrograph by Wilson J. Ribot, USAMRIID

By modifying an enzyme produced by the bacterium that causes anthrax, US Army scientists were able to protect mice from infection with the deadly disease. 

Their findings, published in Science Translational Medicine, suggest a potential therapeutic strategy for treating multidrug-resistant strains of anthrax, and could aid in the development of new treatments for other bacterial infections.

Bacillus anthracis, the bacterium that causes anthrax, is one of the most significant bioterrorism threats, as well as a public health challenge in many places around the world. Its disease-causing capability arised from three main components – lethal toxin, oedema toxin, and the capsule. Researchers in this study developed a method to degrade the capsule surrounding the bacterium, allowing it to be ingested and destroyed by white blood cells, reducing virulence.

There is increasing concern about strains of anthrax that appear to be resistant to treatment with known antibiotics, said Arthur M. Friedlander, MD, the paper’s senior author. He and his team explored alternative treatment approaches that do not rely on the use of antibiotic drugs.

One promising avenue is to make the bacterium more susceptible to the innate immune system. Enzymes known as capsular depolymerases, which are naturally produced by several classes of bacteria, have emerged as a potential new line of antivirulence agents.

“Identification of the capsule depolymerase enzyme within the anthrax bacillus led us to attempt to use that enzyme to remove the capsule,” said Friedlander. “When this proved successful, we utilised recombinant DNA technology and protein engineering methods to engineer and reconfigure the enzyme in new ways.”

Those “engineering changes” included enhancing stability and making production easier, and pegylation, to improve pharmacokinetics. The team then tested the pegylated enzyme, known as PEG-CapD-CPS334C, to be sure it had retained its enzymatic activity.

In the study, 10 out of 10 mice infected with anthrax spores from a nontoxigenic encapsulated strain were completely protected after treatment with PEG-CapD-CPS334C, compared to only 1 of 10 control mice surviving. Similarly, treatment of mice infected with a fully virulent encapsulated strain using PEG-CapD-CPS334C protected 8 of 10, while only 2 of 10 controls survived.

“This strategy renders B. anthracis susceptible to the innate immune responses and does not rely on antibiotics,” the authors concluded. “These findings suggest that enzyme-catalysed removal of the capsule may be a potential therapeutic strategy for the treatment of multidrug-resistant anthrax and other bacterial infections.”

It could also allow the treatment of soldiers exposed to anthrax through natural means or enemy attacks.

Source: EurekAlert!

Categories : Hospitals PaediatricsTags :

One-sixth of Patients in PICUs Harmed by Medications

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One-sixth of children in paediatric intensive care units (PICUs) were harmed by medications, of which most cases were preventable, according to a new study published in the British Journal of Clinical Pharmacology.

Researchers conducted an observational study across three PICUs in England over a three-month period in 2019.

The study included 302 patients and 62 adverse drug events were confirmed. The estimated incidence of adverse drug events were 20.5 per 100 patients, and most were preventable as judged by the expert panel. ADEs were commonly involved with medicines prescribing (46.8%) and caused temporary patient harm (67.7%). 

Medications for the central nervous system (22.6%), infections (20.9%), and the cardiovascular system (19.4%) were commonly implicated with adverse drug events. Analysis revealed that patients who stayed in PICU for seven or more days were more likely to experience an adverse event compared to patients with a shorter stay. 

“This multicentre study is the first of its kind in the UK hospitals, and its findings can guide future remedial interventions to reduce avoidable medication-related harm in this vulnerable patient population,” said lead author Anwar A. Alghamdi, PhD, of the University of Manchester.

Source: Wiley