The Pathobiome: A New Framework to Understanding Diseases Better

 

 

|| Monday: September 16: 2019 || ά.  CEFAS and University of Exeter scientists have presented a new concept, describing the complex microbial interactions, that lead to disease in plants, animals and humans. Microbial organisms and viruses cause many diseases of plants and animals.

They can, also, help protect life from diseases, for example, the complex communities of microbes in the human gut, which are very important for our health. However, very little is known about these microbes and how they cause and prevent disease.

The ‘pathobiome’ concept opens a door on this unexplored world of microbial diversity and how it controls all other organisms on the planet. It will change the way we approach health and disease control in animals, plants and humans.

Traditional approaches to describe infectious disease in plants, animals and in humans are based on the concept that single pathogens are responsible for the signs or symptoms of disease observed in those hosts. The pathobiome concept sees to offer another explanation: according to this concept, disease occurrence in reality is much more complex.

The concept acknowledges that all organisms are, in fact, complex communities of viruses, microbes and other small organisms, e.g, parasites, which can interact to affect health or disease status at any given time.

These complex communities continually interact with their hosts, sometimes, conferring benefits, e.g, good bacteria in the human gut microbiome and, at other times, causing harm by contributing to disease. When these communities combine to cause disease they are termed ‘pathobiomes’, a recognition of their collective shift away from the healthy-state ‘symbiome’.

The recognition that the pathobiome plays a key role in those signs and symptoms of disease, that we observe in the host, is becoming a more accurate way of considering disease than by simply referring to it as the outcome of the effects of a single pathogen, e.g., the influenza virus.

Even, when a single agent is implicated, its effects are likely to be modified, enhanced or mitigated by others in the accompanying pathobiome and so should not be considered in isolation in the disease process. The influence of the surrounding environment on animal and plant health is hugely important as well.

For example, aquatic organisms live in a microbial soup; there are millions of microbes and viruses in every drop of fresh and seawater. Some of these are already known to cause diseases in different organisms.

In other cases, microbes not previously thought to be pathogenic can, in fact, become so under certain environmental conditions. ‘As a result of this we are revising our understanding of what a pathogen actually is as we start to recognise that this can be determined by the context, in which a microbe finds itself.

Professor David Bass, the Lead Author at CEFAS, said: “The vast majority of cells in our bodies are bacterial, not human. “Therefore, we are walking eco-systems, interacting communities of many different organisms. This is, also, true for all other animals and plants. The organisms in these complex communities play key roles in determining the health of their host animals and plants.

The pathobiome concept will lead to understanding these relationships better and help us manage disease in crop plants and animals, wildlife, pets and ourselves.”

Professor Charles Tyler, of the University of Exeter, said, “As we seek to better understand how pathogens cause diseases, we increasingly recognise that the environment, of both the host and pathogen, plays a vital role.

The concept of the pathobiome seeks to understand how interactions between organisms in and immediately surrounding, a host, together with the associated physico-chemistries of those environments enable or inhibit an organisms’ ability to cause disease.

As such, this presents a more holistic and realistic approach to understanding the disease process. It is great to see this conceptual paper coming out of the Centre for Sustainable Aquaculture Futures, a partnership between the University of Exeter and CEFAS, where disease diagnosis, avoidance and mitigation of disease in aquaculture is a major focus.”

Professor Grant Stentiford, Co-author and Science Theme Lead for Animal and Human Health at CEFAS, said, “Conceptualising the pathobiome as a community of microbes, which have the capacity to change in the host over space, e.g, between tissues and organs and time and are associated with observable changes in the health of the host, will revolutionise our understanding of how to describe and manage disease in animals and plants.

In the case of farmed animals and plants, optimising those conditions, which discourage formation of a pathobiome, may, become as important as existing controls, which aim to minimise exposure to single, specific pathogens.”

The Paper has been published in the journal Trends in Ecology and Evolution: The pathobiome in animal and plant diseases.”:::ω.

Readmore

|| reginehumanicsfoundation.com || 160919 || Up ||

 

 

 

 

 

Let Us Put This to This Utterly Arrogant Age of Humanity That Believes and Behaves As If We Know It All and That Values Education Learning and Development the Least: A Collection of 100 Trillion Micro-organisms Live in Each and Every Human Being: How Long Will It Take for Us to Have an Atlas Made About These 100 Trillion Entities: We Know So Little of Them That Researchers Have Discovered a New Giant Bacterial Virus in Human Gut and It Infects Bacteria: Here Is the Megaphage Lak

|| January 29: 2019: UCL News || ά. A new giant virus, that infects bacteria, commonly, found in the human gut, has been discovered by an international team led by researchers from UCL and UC Berkeley. The new ‘megaphage’, called, ‘Lak’, is the same size as some bacteria and is the biggest ever reported phage found in the human gut. A Study, published in Nature Microbiology, describes the discovery of Lak phage and reports that they, specifically, infect bacteria, called, Prevotella, which live in all people but, most notably, those, who have a traditional ‘hunter gatherer’ high in fibre and low in fat diet.

Prevotella is, also, associated with upper respiratory tract infections and is prevalent in periodontal disease, which means the new megaphage, may, open up the development of new phage-based treatments for infections, caused by Prevotella. “Despite the high prevalence of phage in our environment and bodies, we still have much to learn about the role they play in the human microbiome, the collection of 100 trillion micro-organism, that live in each of us.” said the Study Co-author Professor Joanne Santini, UCL Structural and Molecular Biology.

“Phage could be, really, important in regulating the populations of micro-organisms, living in our bodies but more research is needed to understand how these viruses affect our health, for better or worse. Phage could be killing bacteria, that would, otherwise, cause infections or they could be attacking bacteria, that benefit us; we don’t know.”

While Prevotella is, commonly, found in many populations, the researchers discovered the Lak phage, living in the guts of people, who are living in rural Baangladesh and the Hadza tribe in Tanzania, who subsist, mostly, on vegetables and some seafood but eat very little meat, sugar and fat.

Lak phage populations were, also, found in the guts of baboons and a pig, demonstrating that phage, which can carry human health-relevant genes, can move between humans and animals and perhaps carry disease. Phage are known to carry genes, that exacerbate many human illnesses. They can carry genes, that encode botulism, cholera and diphtheria toxins, for example, making symptoms much worse for those infected with the bacteria.

“Phage are well-known to carry genes, that cause disease and genes, that code for antibiotic resistance.” said the Study’s Lead Author, Professor Jill Banfield, UC Berkeley.

“The movement of megaphage along with the movement of their host bacteria raises the possibility that disease, also, can move between animals and humans and the capacity for this is much larger with megaphage.” And because megaphage, which, most, biologists do not consider to be ‘living’, are bigger than life-forms like bacteria, they blur the distinction between what is alive and what isn’t.

These huge entities fill the gap between what we think of as non-life and life and in a sense, we have, mostly, missed them.” The megaphage were discovered while Professor Santini was sequencing gut bacteria from people in Baangladesh to explore the effects of arsenic-tainted water on intestinal flora.

By reassembling their entire genomes, Professor Banfield saw that all of them were 10 times bigger than the average phage encountered in other microbiomes at 550 kilobase pairs. Using a method, called, CRISPR, the research team found that Prevotella contained snippets of megaphage DNA, suggesting that Lak prey on Prevotella but they found no evidence that it integrated its genes into the genome of Prevotella.

In two Baangladeshis, whose gut microbiomes were sampled, scientists found changing levels of phage and Prevotella over time, indicating a constant cycle where rising populations of phage drive down bacterial populations, followed by a drop in phage, that allows Prevotella to rebound.

“We see a classic predator-prey interaction between Lak phage and Prevotella. It uses the bacteria to replicate itself before destroying the infected bacterial cell and its membrane to release the newly made megaphage into the environment.” said Professor Santini.

“We don’t know what impact this has on the human host or how widespread the phage is but, the next step is to isolate it and characterise it further to find out. We, also, aim to find out whether it is transmitted from parent to offspring or between humans and animals.”

The researchers now plan to see how populations of phage and the bacteria they prey on in the gut change over time and with diet and how that affects health.

The Paper: Megaphages infect Prevotella and variants are widespread in gut microbiomes: Audra E. Devoto, Joanne M. Santini, Matthew R. Olm, Karthik Anantharaman, Patrick Munk, Jenny Tung, Elizabeth A. Archie, Peter J. Turnbaugh, Kimberley D. Seed, Ran Blekhman, Frank M. Aarestrup, Brian C. Thomas and Jillian F. Banfield: Published in Nature Microbiology:::ω.

|| Readmore || 300119 || Up || 

A Hive for the Honey and a Vaccine for the Honey Bees: That’s What A Bee Calls PrimeBEE

|| November 01: 2018: University of Helsinki News: Elina Raukko Writing || ά. An easily administered edible vaccine could keep the pollinating bees safe from bacterial diseases and give invaluable support for food production worldwide. Food and pollination services are important for everyone: humans, production animals and wildlife alike. Inventing something, that guards against pollinator losses will have a tremendous impact. PrimeBEE is the first-ever vaccine for honey bees and other pollinators.

It fights severe microbial diseases, that can be detrimental to pollinator communities. The invention is the fruit of research carried out by two scientists in the University of Helsinki, Dalial Freitak and Heli Salmela. The basis of the innovation is quite simple. When the queen bee eats something with pathogens in it, the pathogen signature molecules are bound by vitellogenin. Vitellogenin, then, carries these signature molecules into the queen’s eggs, where they work as inducers for future immune responses.

Before this, no-one had thought that insect vaccination could be possible at all. That is because the insect immune system, although, rather similar to the mammalian system, lacks one of the central mechanisms for immunological memory, antibodies. "Now we've discovered the mechanism to show that you can actually vaccinate them. You can transfer a signal from one generation to another." Ms Dalial Freitak, Researcher says.

Ms Dalial Freitak has been working with insects and the immune system throughout her career. Starting with moths, she noticed that, if, the parental generation is exposed to certain bacteria via their food, their offspring show elevated immune responses.

"So, they could actually convey something by eating. I just didn't know what the mechanism was. At the time, as I started my post-doc work in Helsinki, I met with Heli Salmela, who was working on honeybees and a protein, called, vitellogenin. I heard her talk and I was like: OK, I could make a bet that it is your protein, that takes my signal from one generation to another. We started to collaborate and that was actually the beginning of PrimeBEE." Ms Dalial Freitak says.

PrimeBEE's first aim is to develop a vaccine against American foulbrood, a bacterial disease, caused by the spore-forming Paenibacillus larvae ssp. larvae. American foulbrood is the most widespread and destructive of the bee brood diseases.  

"We hope that we can, also, develop a vaccination against other infections, such as, European foulbrood and fungal diseases. We have already started initial tests. The plan is to be able to vaccinate against any microbe."

At the same time as the vaccine’s safety is being tested in the laboratory, the project is being accelerated towards launching a business. Ms Sara Kangaspeska, the Head of Innovation at Helsinki Innovation Services HIS, has been involved with the project right from the start.

"Commercialisation has been a target for the project from the beginning. It all started when Dalial and Heli contacted us. They first filed an invention disclosure to us describing the key findings of the research. They, then, met with us to discuss the case in detail and, since then, the University has proceeded towards filing a patent application, that reached the national phase in January 2018.”

A big step forward was to apply for dedicated commercialisation funding from Business Finland, a process, which is co-ordinated and supported by HIS. HIS assigns a case owner for each innovation or commercialisation project, who guides the project from A to Z and works hands-on with the researcher team.

“HIS core activities are to identify and support commercialisation opportunities stemming from the University of Helsinki research. PrimeBEE is a great example of an innovation maturing towards a true commercial seed ready to be spun-out from the University soon. It has been inspiring and rewarding to work together with the researchers towards a common goal.” says Ms Sara Kangaspeska.

"We need to help honey bees, absolutely. Even, improving their life a little would have a big effect on the global scale. Of course, the honeybees have many other problems as well: pesticides, habitat loss and so on, but diseases come hand in hand with these life-quality problems. If, we can help honey bees to be healthier and, if, we can save even a small part of the bee population with this invention, I think, we have done our good deed and saved the world a little bit." Ms Dalial Freitak says. :::ω.

|| Readmore  || 011118 || Up || 

Breast Feeding Protects Infants From Antibiotic Resistant Bacteria

|| October 14: 2018: University of Helsinki News: Anu Partanen Writing || ά. A new study shows that babies, that are breastfed for at least six months, have less antibiotic-resistant bacteria in their gut compared with infants breastfed for a shorter time. In addition, antibiotic use by mothers increases the number of antibiotic-resistant bacteria in infants. Bacteria resistant to antibiotics are everywhere. They are present in the human gut, regardless of whether a person has taken antibiotics. They are transmitted between individuals in the same way as bacteria, viruses and other micro-organisms usually are: through, for example, direct contact and in food.

A recent study completed at the University of Helsinki investigated the amount and quality of bacteria resistant to antibiotics in breast milk and the gut of mother-infant pairs, resulting in three findings. First, infants, who were breastfed for at least six months had a smaller number of resistant bacteria in their gut than babies, who were breastfed for a shorter period or not at all. In other words, breastfeeding seemed to protect infants from such bacteria. Second, antibiotic treatment of mothers during delivery increased the amount of antibiotic-resistant bacteria in the infant gut. This effect was still noticeable six months after delivery and the treatment.

The third finding, meanwhile, was that breast milk, also, contains bacteria resistant to antibiotics and that the mother is likely to pass these bacteria on to the child through milk. Nevertheless, breastfeeding reduced the number of resistant bacteria in the infant gut, an indication of the benefits of breastfeeding for infants. The findings were published in the journal Nature Communications.

The increasingly frequent occurrence of bacteria resistant to antibiotics is among the greatest global threats to human health. According to estimates by previous research, bacteria and other micro-organisms resistant to antibiotics and other drugs will, by 2050, cause more deaths than cancer, since infections can no longer be effectively treated.

Microbiologist Katariina Pärnänen of the University of Helsinki’s Faculty of Agriculture and Forestry investigated with her colleagues the breast milk and faecal matter of 16 mother-infant pairs. The DNA in the milk and faeces were sequenced or their genetic code decoded. However, the study did not focus on the mother’s DNA found in milk. Rather, the researchers focused on the bacterial DNA and genes in the milk. They created the most extensive DNA sequence library of breast milk thus far.

“Such studies were practically impossible only a few years ago. For instance, the laboratory techniques required for processing DNA into sequenceable form have advanced to the extent that the amount of source material needed is today a thousand times smaller than, say, five years ago.” Dr Pärnänen.

The specific focus of the study was the number of antibiotic resistance genes:ARGs. Such genes make bacteria resistant to certain antibiotics and they are, often, able to transfer between bacteria. Individual bacteria can have several antibiotic resistance genes, making them resistant to more than one antibiotic. The study demonstrated, for the first time, that breast milk, indeed, contains a significant number of genes, that provide antibiotic resistance for bacteria and that these genes, as well as, their host bacteria, are most likely transmitted to infants in the milk.

Mothers transmit antibiotic-resistant bacteria residing in their own gut to their progeny in other ways as well, for example, through direct contact. Yet, only some of the resistant bacteria found in infants originated in their mothers. The rest were likely from the environment and other individuals.

The study does, however, support the notion that breastfeeding overall is beneficial for infants. Although, breast milk contains bacteria resistant to antibiotics, sugars in the milk provide sustenance to beneficial infant gut bacteria, such as, Bifidobacteria, which are used as probiotics.

Breast milk helps such useful bacteria gain ground from resistant pathogens, which is, probably, why infants, who were nursed for at least six months have less antibiotic-resistant bacteria in their gut compared to infants, who were nursed for a shorter period.

“As a general rule, it could be said that all breastfeeding is for the better.” says Dr Pärnänen. “The positive effect of breastfeeding was identifiable, also, in infants, who were given formula in addition to breast milk. Partial breastfeeding already seemed to reduce the quantity of bacteria resistant to antibiotics. Another finding was that nursing should be continued for at least the first six months of a child’s life or even longer. We have already known that breastfeeding is all in all healthy and good for the baby but we now discovered that it, also, reduces the number of bacteria resistant to antibiotics.”

Women can be prescribed an intravenous antibiotic treatment during labour for various reasons, for example, if, they have tested positive for Streptococcus, a bacterium hazardous to infants. In such cases, antibiotic treatment is intended to prevent the transmission of bacteria living in the birth canal to the infant during delivery.

Antibiotic treatment can, also, be used, if, the mother’s waters have broken long before labour begins or, if, potential infection is otherwise suspected. However, the study indicated that the antibiotic treatment of the mother increases the number of bacteria resistant to antibiotics in the infant’s gut.

While the study did not demonstrate why this happens, according to one theory, the bacteria, that first reach the infant gut gain a head start. Since antibiotics administered to the mother eliminate all bacteria except those resistant to the drug, in such deliveries the mother is likely to pass mainly resistant bacteria on to her child.

“We can not advise that mothers should not be given antibiotics during delivery.” says Dr Pärnänen. “The consequences of infection for both mother and infant are potentially serious. What we can state is our findings and physicians can use them to consider whether practices should be changed or not.”

However, antibiotic treatment administered during delivery is only one of all the antibiotic courses taken by mothers at some point in their life, that, ma,  impact the gut microbiota of infants. The bacterial flora in our gut changes every time we take antibiotics. Antibiotics kill both good and bad bacteria, leaving alive only those bacteria, that are resistant to the antibiotic in question. These bacteria, may, gain a permanent foothold in the gut, even, though, most of the other bacteria will return soon after the antibiotic treatment as well.

Since the mother transmits bacteria resistant to antibiotics to the infant, all of the antibiotic courses taken by the mother in her life, may, also, affect the bacterial flora of the infant’s gut and the prevalence of resistant bacteria in the gut. All resistant bacteria do not cause diseases and, thus, do not, as such, harm their carriers. In suitable conditions, however, such bacteria can either induce the onset of a disease or transfer the gene, that provides antibiotic resistance to another bacterial pathogen.

Because such bacteria can not be killed with antibiotics and because the immune system of infants is weak, infections caused by resistant bacteria can be fatal to infants. In Finland, where Dr Pärnänen is based, babies die of such infections only rarely. Yet, prior studies show that, globally, more than 200,000 new-borns die annually of infections, caused by antibiotic-resistant bacteria, that have advanced to the stage of sepsis.

“Babies inherit every facet of antibiotic misuse since the discovery of antibiotics. The amount of bacteria resistant to antibiotics in the infant gut is alarming, since infants are, also, otherwise, vulnerable to diseases. Babies are more likely to suffer from this than adults, even, if, the babies have never been given antibiotics.”

Health problems originating in resistant bacteria are accrued by those with weak immunity. Infants and the elderly are in particular danger. Since the defence system of infants is yet to reach the efficiency of adult immunity, small children often need antibiotics to recover from diseases, which makes antibiotic inefficiency more dangerous to children.

The study was carried out in co-operation between the University of Helsinki, the University of Turku, the Turku University Hospital and the University of Gothenburg.

Dr Katariina Pärnänen will discuss the topic during One Health Finland’s evening on antibiotic resistance on  November 02 at the University of Helsinki Think Corner. The World Antibiotics Awareness Week runs from November 12 to 18.

The Paper: Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements:::ω.

|| Readmore  || 141018 || Up || 

Here You Go Virtanen With Your Own Bacterium: And What Is It Called The Humanion: Well It Is Acidipropionibacterium Virtanenii: That’s a Grand Name for a Bacterium: Well They Would Say It Is All Your Fault Because You Discovered It: Well I Can Not Do Much About That Now Can I

|| September 17: 2018: University of Helsinki News || ά. Artturi Ilmari Virtanen narrowly missed out on species naming for his original work in the 1920s. Now he has got Acidipropionibacterium Virtanenii named after him. Virtanen is best known for his work on fodder preservation method, which earned him a Nobel Prize award in Chemistry in 1945. What is rarely mentioned in his biographies, is his pioneering research on Propionic Acid Bacteria:PAB.

PAB, named collectively for their production of propionic acid as the main end product of fermentation, which includes several species of important bacteria: from the vitamin B12-producer and emerging probiotic Propionibacterium Freudenreichii, through industrial producer of propionic acid Acidipropionibacterium Acidipropionici, to opportunistic human pathogen Cutibacterium Acnes.The first reports of PAB being isolated and described came at the very beginning of the 20th century. In the early 1920s, Virtanen, also, worked on characterisation of strains he isolated from the brown spots of Finnish Emmental-type cheeses.

However, it was not until 1928 that a breakthrough in PAB research came with the doctoral thesis of Cornelius Bernardus van Niel from the Delft University of Technology, where systematic classification and species naming took place. To honour the researchers, who either first isolated or contributed to the understanding of the biology of PAB, van Niel named the species after the scientists, who discovered them, among them Eduard von Freudenreich:Freudenreichii, Sigurd Orla-Jensen:Jensenii, Gerda Troili Petersson:Peterssonii, James M. Sherman:Sshermanii and J. Thön:Thoenii.

However, Virtanen missed out on a species name, as he himself believed that his strains belonged to already described and named Acidipropionibacterium Thoenii. In the University of Helsinki, during sequencing project of PAB isolated from various environments, researchers worked with a PAB strain isolated from Finnish malted barley, which displayed similar pigmentation and branching cell shape to those described by Virtanen. As it turned out the, the strain was sufficiently genetically different from A. Thoenii and its known relatives to form a new species.

"While we have no way of knowing whether the novel species isolated in Finland could be, in fact, the species Virtanen described in his work, we still decided to name the novel species Acidipropionibacterium Virtanenii in his honour and to ensure Virtanen’s name is recognised among those, who contributed to the pioneering PAB research." says Dr Paulina Deptula, Postdoctoral Researcher in the Faculty of Agriculture and Forestry.

The Paper: Paulina Deptula,  Olli-Pekka Smolander,  Pia Laine,  Richard J. Roberts,  Minnamari Edelmann,  Petri Peltola,  Vieno Piironen,  Lars Paulin,  Erna Storgårds,  Kirsi Savijoki,  Arja Laitila,  Petri Auvinen, Pekka Varmanen. Acidipropionibacterium virtanenii sp. nov. isolated from malted barley. International Journal of Systematic and Evolutionary

Image: Paulina Deptula:University of Helsinki:::ω.

|| Readmore  || 180918 || Up || 

We Alter Together As We Evolve Together: The Duality That It Is

|| September 12: 2018: University of Exeter News || ά. A study of a songbird and a bacterium, that infects it has showed how species in conflict evolve in response to each other. University of Exeter researchers found North American house finches developed greater resistance to a bacterial pathogen, Mycoplasma Gallisepticum, thereby, pushing the pathogen to become more virulent. This process is known as ‘host-pathogen co-evolution’, which is believed to play a key role in evolution but until now evidence for it has been scarce.

“Our results show how these competitors respond to each other over time.” said Dr Camille Bonneaud, of the Centre for Ecology and Conservation on the University of Exeter’s Penryn Campus in Cornwall. “As the finches evolve better resistance to the pathogen, the pathogen becomes more potent to overcome these defences. It is widely assumed that animals, including, humans, co-evolve with their infectious pathogens and become ever more resistant but, in fact, most direct evidence for this comes from studies of bacteria and their viral pathogens.

In this study we show how a pathogen can shape evolution in a vertebrate and how this has consequences for the pathogen.” The research, supported by Auburn University, Alabama and Arizona State University, was made possible by differences in finch populations in these two US states.

House finches in Arizona have not been exposed to Mycoplasma Gallisepticum, while those in Alabama have been exposed to it for over 20 years. Researchers found that exposure to the pathogen led to eye swelling in birds from both states but that resistant Alabama birds were three times less likely to show symptoms, that would lead to death in the wild.

Similarly, the pathogen evolved to become better able to infect and transmit as the birds became more resistant. The findings have implications for our knowledge of diseases that affect humans.

Dr Bonneaud said, “The Plague and more recently the pandemic of HIV are sobering reminders of the impacts that emerging infectious diseases can have on us. We know that we can see the signature of such impacts on our genome.

This study provides a direct demonstration that these outbreaks can shape our evolution and that how we respond will, in turn, shape the evolution of our infectious pathogens.” 

The Paper: Published in the journal Current Biology: Rapid antagonistic coevolution in an emerging pathogen and its vertebrate host :::ω.

|| Readmore  || 130918 || Up ||