Friday, 23 June 2017

Chemical purity regulatory findings

New Applications for Certificates of Suitability (CEP) for chemical purity (Top 10 deficiencies)

The EDQM has issued a document that summarises the ten most frequent questions raised after the initial evaluation of new applications for Certificates of suitability (CEP) for chemical purity.

In the document, the top ten most frequent questions are listed together with expectations and recommendations on how to address the specific deficiencies, with reference to applicable guidelines.

This document is intended to help applicants to improve the quality of their dossiers, in order to facilitate and speed up the granting of their CEPs. The information should be taken into account while building up a dossier, in combination with the EDQM Guideline “Content of the Dossier for Chemical Purity and Microbiological Quality (PA/PH/CEP 04 1)” available on the EDQM website.

The top 10 deficiencies are:

  1. Absence or deficient discussion on the risk of having potential mutagenic impurities in the final substance.
  2. Absence or insufficient discussion on fate and carryover of related substances of starting materials (included) to the final substance.
  3. Lack of details and/or poor description of the manufacturing process of the substance from the introduction of starting materials
  4. Non-acceptable starting materials, necessity to redefine them earlier in the process.
  5. Non-adequate or poorly justified specifications in place to control the quality of starting materials
  6. Non-adequate or missing specifications (and analytical methods) for reagents and solvents (recovered and recycled included) used to manufacture the substance from the introduction of starting materials.
  7. Non-adequate or missing discussion on carryover of reagents and elemental impurities to the final substance.
  8. Non-adequate or poorly justified specifications in place to control the quality of isolated intermediate.
  9. Absence or insufficient discussion on fate and carryover of impurities from synthetic intermediates (included) to the final substance.
  10. Non-adequate or missing information on the synthesis of starting materials and their manufacturers
For further details see EDQM:

Posted by Dr. Tim Sandle

Thursday, 22 June 2017

Guidance on quality of water for pharmaceutical use

Concept paper on the need for revision of note for guidance on quality of water for pharmaceutical use

Up to now, the production of Water for Injections (WFI) had been limited to distillation only. The revision of the monograph for Water for Injections (0169) allows for production of WFI by a purification process equivalent to distillation such as reverse osmosis, coupled with appropriate techniques. This brings the Ph. Eur. more closely in line with the US Pharmacopeia and the Japanese Pharmacopoeia which allow for production of WFI by distillation or a purification process proven being equal or superior to distillation, and by distillation or reverse osmosis followed by ultrafiltration.

A new concept paper has been issued by the European Medicines Agency: “This concept paper addresses the need to update and revise the Note for Guidance on Quality of water for pharmaceutical use (CPMP/QWP/158/01 EMEA/CVMP/115/01). This guideline was originally adopted in May 2002 and came into operation on 1st June 2002.

Since then, there have been ongoing discussions for many years as to whether there is a need to include non-distillation technologies as a method for production of water for injections (WFI) and eventually, during its 154th Session, the Ph. Eur. Commission adopted a revision of the monograph for Water for Injections (0169) allowing the use of non-distillation technologies for WFI production (the revised monograph will be published in the Ph. Eur. Supplement 9.1 and will become effective in April 2017).

For further details see: EMA

Posted by Dr. Tim Sandle

Wednesday, 21 June 2017

Why we get diarrhea

Does diarrhea serve a purpose? Does it actually help clear the bacteria causing a gastrointestinal infection, or is it merely a symptom of disease that should be prevented as much as possible? In a new study from Brigham and Women's Hospital, investigators explore the immune mechanism that drives diarrhea, concluding that it does play a critical role in pathogen clearance in the early stages of infection. A new study also uncovers a previously unrecognized role for interleukin-22, an immune system molecule, in the host's defense against infection.

To investigate, researchers used a mouse model infected with Citrobacter rodentium, the mouse equivalent of an E. coli infection. Using this model, they saw an increase in the permeability of the intestinal barrier within just two days of infection -- well before inflammation and epithelial damage. In particular, they uncovered a critical role for interleukin-22 that in turn influences another molecule called claudin-2, previously known to be involved in causing diarrhea. They found that diarrhea resulting from the signaling of these two molecules helped promote pathogen clearance and limited disease severity.

Other investigators have proposed developing new therapeutics to inhibit claudin-2. However, Turner and colleagues explain that the activation of this pathway may be critical for combating an infection, particularly in the early stages of a disease. They conclude that diarrhea is critical to enteric pathogen clearance, and that IL-22 may play a key role in host defense.


Tsai PY et al. L-22 upregulates epithelial claudin-2 to drive diarrhea and enteric pathogen clearance. Cell Host & Microbe, 2017 DOI: 10.1016/j.chom.2017.05.009

Posted by Dr. Tim Sandle

Test for Abnormal Toxicity

The scientific validity and rationale of the test for abnormal toxicity has been the subject of debate for some time in Europe. The test was originally developed for detecting external contaminants in biological products, but over time the introduction of Good Manufacturing Practices and the use of appropriate and stringent Quality Control measures have rendered their use less necessary. Current scientific evidence suggests that, in light of such debatable relevance, the omission of the test for abnormal toxicity would not compromise the safety of biological medicines.

The European Pharmacopeia is considering the possible deletion from the European Pharmacopoeia. The European Pharmacopoeia Commission is seeking public feedback on its proposal to remove the requirements for a test for abnormal toxicity from 49 monographs of the European Pharmacopoeia (Ph. Eur.).

This consultation will run until June 2017 for all users, and will be extended until August for National Pharmacopoeia Authorities.


Posted by Dr. Tim Sandle

Tuesday, 20 June 2017

FDA - Burkholderia cepacia complex poses a contamination risk

FDA warned drug manufacturers on May 22, 2017 about a series of product recalls involving Burkholderia cepacia complex (BCC) contamination. BCC is a water-borne pathogen that can be found in pharmaceutical water systems. According to FDA, it can be a challenge to detect BCC, and validated testing methods should take the “unique characteristics of different BCC strains” into consideration.

The FDA advises drug manufacturers of non-sterile, water-based drug products that there have been recent product recalls due to Burkholderia cepacia complex (BCC or B. cepacia) contamination.(1, 2, 3) BCC and other water-borne opportunistic pathogens are among the contaminants that can be found in pharmaceutical water systems.

BCC can survive or multiply in a variety of non-sterile and water-based products because it is resistant to certain preservatives and antimicrobial agents.(4, 5) Detecting BCC bacteria is also a challenge and requires validated testing methods that take into consideration the unique characteristics of different BCC strains.

People exposed to BCC are at an increased risk for illness or infection, especially patients with compromised immune systems.(3, 6)

Specifically, the FDA is reminding drug manufacturers to:

  • Establish procedures designed to prevent objectionable microorganism contamination of non-sterile drug products, such as procedures to assure adequate quality of incoming materials, sanitary design, maintenance and cleaning of equipment, production and storage time limitations, and monitoring of environmental conditions (21 CFR 211.113(a)).7
  • Use scientifically sound and appropriate acceptance criteria (e.g., USP Chapter <1111> Microbiological Examination of Non-sterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use)8 and test procedures (e.g., USP <61>/<62> Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests and Tests for Specified Microorganisms, respectively) to assure that drug product components (including pharmaceutical water) and finished drug products conform to appropriate quality standards (21 CFR 211.160(b)).
  • Provide appropriate drug product specifications (tests, methods, and acceptance criteria) in applications submitted to the FDA (21 CFR 314.50(d)(1) for new drug applications, or 21 CFR 314.94(a)(9) for abbreviated new drug applications). As appropriate, additional laboratory tests may be needed to determine whether products are suitable for release.
  • Ensure that the methods used to test finished drug products prior to release for distribution are appropriately validated, accurate, sensitive, specific and reproducible (21 CFR 211.165).
  • Test in-process materials during the production process (e.g., at commencement or completion of significant phases, or after storage for long periods), using valid in-process specifications to assure, among other things, that the drug product will meet its final specification, including criteria for absence of microbial contamination, where appropriate (21 CFR 211.110).
  • Investigate any failure to meet specifications, including other batches of the same drug product and other drug products that may have been associated with the specific failure or disrepancy(21 CFR 211.192), and implement appropriate corrective and follow-up actions to prevent recurrence.
  4. Torbeck L, D. Raccasi, D.E. Guilfoyle, R.L. Friedman, D. Hussong. 2011. Burkholderia cepacia: This Decision is Overdue. PDA J. Pharm. Sci. Tech., 65(5): 535-43.
  6. Hutchinson, J., W. Runge, M. Mulvey, G. Norris, M. Yettman, N. Valkova, R. Villemur, and F. Lapine. 2004. Burkholderia cepacia infections associated with intrinsically contaminated ultrasound Gel: The role of microbial degradation of parabens. Infec. Cont. Hosp. Epid., 25: 291-296.
  7. As noted in the preamble to the 1978 CGMP final rule, parts 210/211, “Microorganisms could be objectionable by virtue of their total numbers or their detrimental effect on the product or by their potential for causing illness in the persons ingesting them. A definition of the term is not practical in the regulations, however, because the objectionable nature of a microorganism may develop only in relation to the unique circumstances of a particular formulation, a particular ingredient, a particular method of manufacture, or the conditions found at a particular firm.” 43 FR 45053.
  8. Guidance for Industry: Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions:
Posted by Dr. Tim Sandle

Monday, 19 June 2017

Risk assessment and pharmaceutical processing hazards

Pharmaceutical medicines are expected to be efficacious and to perform according to the product licence or as directed by the medical practitioner. Medicines are also expected to be safe, and the basis of a safe medicine is one that has been manufactured consistently and with a review of potential manufacturing hazards completed.

In relation to the issue of hazards, Tim Sandle has written a review for Microbioz India of the types of hazards common to pharmaceutical manufacturing (including microbial and chemical) and the risk mitigations that can be deployed to address them. This includes consideration of risk assessment tools and techniques.

The reference is:

Sandle, T. (2017) Risk assessment and pharmaceutical processing hazards, Microbioz India 3 (3): 10-18

For further details, see Microbioz India.

Posted by Dr. Tim Sandle

Sunday, 18 June 2017

Continuous Manufacturing Provides Many Benefits for the Pharmaceutical Industry

Continuous manufacturing is a process people adopted since the beginning of the industrial revolution — production for a product continues for months or years uninterrupted, creating an unbroken supply chain. It’s used in everything from oil refining and power generation to wastewater treatment and the creation of pig iron.

Guest post by Megan Ray Nichols (Schooled by Science)

Continuous manufacturing is one of the most efficient forms of production and it is finally making its way into the pharmaceutical industry. What benefits does continuous manufacturing provide to the pharmaceutical industry?

Continuous Manufacturing in Pharmaceuticals

Traditional manufacturing of pharmaceutical products is done in batches — a single batch of a medication is produced from start to finish. Then the completed batch ships and the process can start all over again from square one.

While some types of pharmaceutical products might still require this, due to chemicals or components that cannot be easily adapted to continuous production styles, many products are fit for continuous production.

This prevents the loss of time that comes with traditional batch production. If your product requires many different steps, each one has to be reset and prepared before the new batch can begin production.

Benefits of Continuous Production
What are the benefits of continuous production? Depending on the type of production, a company may experience:

  • Reduced carbon footprint. Eliminating unnecessary steps, like resetting batch production, helps to reduce waste.
  • Production optimization. In one case, production that normally took more than 200 days was streamlined down to a process that took only two days. 
  • Price reduction. The decrease in production times can be passed on to the consumer in the form of reduced drug costs. This improves patient access by making the drugs more affordable for low income or uninsured individuals. 
  • Higher and more uniform quality. Batch-produced products often vary in quality from batch to batch. Continuous production eliminates that variability by creating a constant uniform product

In many cases, there are no downsides to establishing a continuous manufacturing set up for the production of pharmaceuticals.

Challenges of Continuous Manufacturing

The primary challenge when establishing a continuous manufacturing program in the pharmaceutical industry is that there is already an established manufacturing infrastructure in place. Changing from a batch-based manufacturing system could take both a considerable investment and result in a potential loss of revenue as your manufacturing would be offline during the switch.

For a company that produces multiple different products, the best solution would be to convert the production of one product at a time to continuous manufacturing practices.

There are a number of compounds that will not be able to be converted to continuous manufacturing practices due to the delicate nature of the components. Those will continue to lend themselves to batch manufacturing.

Establishing a Continuous Manufacturing Program

Those looking to implement a continuous manufacturing strategy should look into the makeup of their individual products. Will they translate well to the style of production that allows the pharmaceuticals to be continuously manufactured or are they too delicate to translate well?

If the former is the case, the next step is to formulate a plan that will allow you to switch to a continuous manufacturing program without compromising your supply chain.

The most efficient and cost-effective way to do this is to build on the existing manufacturing infrastructure, but, if doing so compromises your ability to produce and supply your pharmaceutical products, it may be more efficient to build a new continuous manufacturing infrastructure from the ground up.

More efficiently produced medications can be made less expensively, a savings that can be passed on to the consumer and make the medication more accessible to everyone. This can all be accomplished, theoretically, while still maintaining profit margins.

Continuous manufacturing could easily change the shape of pharmaceutical manufacturing if it is adapted on a large scale. Right now, it’s harder for established manufacturers to change their ways, but a fully adapted continuous manufacture could be a boon, not just for the company crafting the pharmaceuticals, but for the consumer as well.

Antibiotics are a potential link to bowel cancer precursor

A new study has found that people who take antibiotics over long time are more at risk of developing growths on the bowel that could be a precursor to cancer.
The research forms part of a wider line of scientific inquiry about the effect that antibiotics and other antimicrobials have on the human digestive tract and that microorganisms that live within it. Antibiotics are designed to kill harmful bacteria but they are not precise and they kill beneficial bacteria as well. If the balance slips too far and too many beneficial bacteria are killed, this imbalance has been linked to adverse health events. The likelihood of this change to the body's microbiome is greater the longer the period of time that a course of medication is taken for. The term microbiome refers to the microorganisms living in a given ecological niche - in this case the human intestines.

Data about long-term antibiotic use and bowel growths comes from a major U.S. trial called the Nurses' Health Study, which reviewed data from 16,000 nurses. The main findings, as summarized by BBC Science, were:
Nurses who took antibiotics for two months or more, aged between of 20 and 39 years, were more likely to be diagnosed with bowel polyps (called adenomas) compared with people who had not taken long-term antibiotics
Nurses who had taken antibiotics for two months or more in their 40s and 50s were even more likely to be diagnosed with an adenoma decades later.
This led the researchers to conclude: "Antibiotics fundamentally alter the gut microbiome, by curbing the diversity and number of bacteria, and reducing the resistance to hostile bugs." This led principal scientist Yin Cao of Harvard University to tell The Tribune: "The findings, if confirmed by other studies, suggest the potential need to limit the use of antibiotics and sources of inflammation that may drive tumor formation."
While the new research, which examines cases of long-term antibiotic use with signs of growth, signals a potential link to cancer, what is being reported is bowel polyps. These are tiny growths on the lining of bowel. These growths are common and they affect around one fifth of the population. In many cases these growths do not cause any symptoms and do not become cancerous. However, some can, if untreated, become cancerous.
The research is published in the journal Gut, in a paper titled "Long-term use of antibiotics and risk of colorectal adenoma."
This is an observational study so no firm conclusions can be drawn about cause and effect. Readers should be aware that this article refers to one study and that further research is needed in this area. Any person on antibiotics should continue with their course and raise any concerns with a medical professional.

Posted by Dr. Tim Sandle

Saturday, 17 June 2017

Can airborne viruses survive in water?

A new study challenges the tenet that herpes viruses, like most enveloped viruses, are relatively unstable outside their host. Under a variety of conditions equine herpesvirus remained stable and infectious over a three week period. This suggests that untreated water could be a source of infection by some herpesviruses.

Enveloped viruses such as herpesviruses can cause disease when spread from host to host by aerosol transmission. They are generally thought to be unstable in the environment, requiring rapid and direct transfer among hosts in order to 'survive' and remain infectious. A research team lead by scientists from the Leibniz Institute for Zoo and Wildlife Research in collaboration with the Institut für Virologie of the Freie Universität Berlin tested this assumption by spiking water with equine herpesviruses under different conditions over a three week period and examining whether viral DNA could be retrieved and to what extent the virus remained infectious after having been in the water.

The results demonstrate that the virus does remain stable and infectious for up to three weeks, with pH and temperature being the two most important factors to determine how long the virus 'survived'. Surprisingly, the addition of soil to the water appeared to "pull" the virus out of the water and stabilize it in the soil, suggesting that in natural water bodies viruses may persist for an extended time without infecting additional hosts. Therefore, in the case of equine herpesviruses, horses or other mammals susceptible to these viruses could be infected by herpesviruses from water bodies long after the animals that shed the virus had left the area.

These results suggest that viruses such as equine herpesviruses may become a part of the environmental "virome" and remain infectious. Equine herpesviruses have spread among mammals such as polar bears and rhinos without direct contact with horses or their relatives in both the wild and in captivity, often resulting in fatal consequences. Shared water sources may be a source and potential vector for infection.

For further details see:

Anisha Dayaram, Mathias Franz, Alexander Schattschneider, Armando M. Damiani, Sebastian Bischofberger, Nikolaus Osterrieder, Alex D. Greenwood. Long term stability and infectivity of herpesviruses in water. Scientific Reports, 2017; 7: 46559 DOI: 10.1038/srep46559

Posted by Dr. Tim Sandle

Friday, 16 June 2017

Foods as a potential source of spread of Clostridium difficile

Foods should be investigated as a potential source of spread of Clostridium difficile, according to research presented at the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).

C. difficile causes gut infections and can be particularly dangerous for elderly patients. Because it is resistant to commonly used antibiotics it can emerge in patients who are already being treated in hospital for unrelated conditions.

The new research used DNA fingerprinting to examine which particular types of the bacteria were causing infections in patients and how widely they are distributed in Europe.

Some strains were found clustered within a particular country, suggesting they were possibly being passed around within hospitals -- a well-recognised route of transmission. However, because some other strains were found dispersed in several different countries, this adds weight to the idea that C. difficile could also be transmitted via our food.

The research was presented by Dr David Eyre, a clinical lecturer at the University of Oxford, United Kingdom. He explained: "We know that C. difficile lives in the gut in a small proportion of healthy people, where it causes no symptoms. However, its resistance to antibiotics means it can grow uncontrollably in patients treated with the drugs, causing diarrhea that can be severe or even fatal. It is the most frequent cause of infectious diarrhea in hospitalised patients, and the increase in the use of antibiotics has allowed C. difficile to spread more effectively.

Posted by Dr. Tim Sandle

Thursday, 15 June 2017

Ocean acidification impairs the nitrogen-fixing bacteria

While increased carbon dioxide levels theoretically boost the productivity of nitrogen-fixing bacteria in the world's oceans, because of its "fertilizing" effect, a new study reveals how increasingly acidic seawater featuring higher levels of this gas can overwhelm these benefits, hampering the essential service these bacteria provide for marine life.

The new data help explain disparities in previous studies exploring the effects of ocean acidification on nitrogen fixation. The abundant cyanobacteria Trichodesmium is estimated to contribute up to 50% of marine nitrogen fixation; therefore, understanding how this species will respond to a changing environment is critical.

Some studies have reported that, under acidified conditions, Trichodesmium significantly increases its rates of nitrogen fixation, photosynthesis and growth, whereas others have documented significant decreases in these processes. Haizheng Hong et al. studied Trichodesmium under controlled conditions, correcting for ammonium and copper contamination (which they say affected some previous results).

They found that increasingly acidic water negatively impacted the bacterium's ability to fix nitrogen. The negative impacts were even more pronounced if iron, an essential nutrient for Trichodesmium, was limited. Further analysis of key bacterial proteins revealed that acidification under iron-limited conditions requires a reallocation of iron among proteins to compensate for the loss of nitrogen-fixation efficiency.

The researchers also sampled Trichodesmium at three stations in the northern South China Sea, where surface iron concentrations are very low; nitrogen fixation was also limited in these locations.


Haizheng Hong, Rong Shen, Futing Zhang, Zuozhu Wen, Siwei Chang, Wenfang Lin, Sven A. Kranz, Ya-Wei Luo, Shuh-Ji Kao, François M. M. Morel, Dalin Shi. The complex effects of ocean acidification on the prominent N 2 -fixing cyanobacterium Trichodesmium. Science, 2017; eaal2981 DOI: 10.1126/science.aal2981

Posted by Dr. Tim Sandle

Wednesday, 14 June 2017

Guide to the preparation, use and quality assurance of blood components (new version)

The EDQM have issued the 19th Edition of the ‘Guide to the preparation, use and quality assurance of blood components’ (Blood Guide).

The 19th Edition of the Guide contains an updated version of the Good Practice Guidelines to fully reflect the most recent changes in good manufacturing practices relevant for blood establishments. The Good Practice Guidelines have been jointly developed by the European Directorate for the Quality of Medicines & HealthCare and the Commission of the European Union. This section of the Guide describes standards and specifications for the quality system to be implemented by blood establishments. In the European Union, Directive (EU) 2016/1214, published in July 2016, requests member states to ensure that blood establishments comply with the Good Practice Guidelines for their quality system by 15 February 2018.

Posted by Dr. Tim Sandle

Tuesday, 13 June 2017

Novel antibiotic resistance gene in milk

A new antibiotic resistance gene has been found in bacteria from dairy cows. This gene confers resistance to all beta-lactam antibiotics including the last generation of cephalosporins used against methicillin-resistant Staphylococcus aureus. A transfer to S. aureus which is likely according to the researchers would jeopardize the use of reserve antibiotics to treat human infections caused by multidrug-resistant bacteria in hospitals.

Macrococcus caseolyticus is a harmless bacterium naturally found on the skin of dairy cows which can spread to milk during the milking process. It can also be present in dairy products made from raw milk like e.g. cheese. Researchers of the Institute of Veterinary Bacteriology of the University of Bern have identified a new methicillin resistance gene in strains of M. caseolyticus isolated from milk. Transfer of the gene to Staphylococcus aureus, a bacterium found on the skin and mucosa of animals and humans, would have dramatic consequences for public health. This methicillin resistance gene would turn this bacteria into a hazardous methicillin-resistant S. aureus (MRSA), which is known to cause difficult-to-treat infections in hospitals. Acquired methicillin resistance in bacteria is associated with genes mecA, mecB, or mecC. However, none of these genes were present in the M. caseolyticus strains -- they carried the novel resistance gene mecD.


Sybille Schwendener, Kerstin Cotting, Vincent Perreten. Novel methicillin resistance gene mecD in clinical Macrococcus caseolyticus strains from bovine and canine sources. Scientific Reports, 2017; 7: 43797 DOI: 10.1038/srep43797

Posted by Dr. Tim Sandle

Monday, 12 June 2017

Chronic fatigue syndrome linked to imbalanced microbiome

Scientists at the Center for Infection and Immunity (CII) at Columbia University's Mailman School of Public Health have discovered abnormal levels of specific gut bacteria related to chronic fatigue syndrome/myalgic encephalomyelitis, or ME/CFS, in patients with and without concurrent irritable bowel syndrome, or IBS. Findings are published in the journal Microbiome.

The study is among the first to disentangle imbalances in the gut bacteria in individuals with ME/CFS and IBS. ME/CFS is a complex, debilitating disorder characterized by extreme fatigue after exertion and other symptoms including muscle and joint pain, cognitive dysfunction, sleep disturbance, and orthostatic intolerance. Up to 90 percent of ME/CFS patients also have IBS.

The researchers followed 50 patients and 50 matched healthy controls recruited at four ME/CFS clinical sites. They tested for bacterial species in fecal samples, and for immune molecules in blood samples.


Dorottya Nagy-Szakal, Brent L. Williams, Nischay Mishra, Xiaoyu Che, Bohyun Lee, Lucinda Bateman, Nancy G. Klimas, Anthony L. Komaroff, Susan Levine, Jose G. Montoya, Daniel L. Peterson, Devi Ramanan, Komal Jain, Meredith L. Eddy, Mady Hornig, W. Ian Lipkin. Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome, 2017; 5 (1) DOI: 10.1186/s40168-017-0261-y

Posted by Dr. Tim Sandle

Sunday, 11 June 2017

Giardiasis may be a disease of the ecology of the GI tract

Colonization by the human and animal parasite, Giardia, changed the species composition of the mouse microbiome in a way that might be harmful.

"This shift is generally characterized by more aerobic bacteria and less diversity of anaerobic species in the gastrointestinal tract," said coauthor Scott C. Dawson, Associate Professor of Microbiology and Molecular Genetics, the University of California, Davis. "This suggests that Giardia infection could -- at least in part -- be an ecological disease, with parasite colonization disrupting the previously stable ecology of the gut."

Indeed, "We found changes in the host microbial community throughout the entire gastrointestinal tract," said Dawson. These findings challenge the conventional wisdom that Giardia is a disease of the small intestine.

"We infected mice with Giardia, sacrificed them at different times post-infection, and sequenced specific regions throughout the entire gastrointestinal tract using high-throughput 16S ribosomal RNA sequencing," said Dawson. This enabled the investigators to quantify the shifts in microbial diversity in each part of the GI tract, following infection. They also pre-treated one cohort of mice with antibiotics, to determine if that pretreatment resulted in different shifts in the microbiome as compared to those in mice not receiving antibiotics (it did so).


N. R. Barash, J. G. Maloney, S. M. Singer, S. C. Dawson. Giardia alters commensal microbial diversity throughout the murine gut. Infection and Immunity, 2017; IAI.00948-16 DOI: 10.1128/IAI.00948-16

Posted by Dr. Tim Sandle