Tag Archives: stress

Night at the Vet College

Step inside the Royal Veterinary College’s inspiring campus on 22nd November for an evening of animal excitement at ‘Night at the Vet College’, in collaboration with The Physiological Society.

The theme of the night is ‘Wellbeing’, based on The Physiological Society’s 2017 theme of ‘Making Sense of Stress’. Complete with canine scientists, TV stars and a dissection, this event is not to be missed!

Wellbeing 2017 image crop

Go behind the scenes at the RVC’s 226 year old Camden campus, admiring animal skeletons and specimens which have shaped the study of thousands of veterinary students. In the main Anatomy Museum you have the chance to get up close and personal with your favourite specimen for a drawing session, with artist Tim Pond.  Tim has drawn every animal under the sun, and will be showcasing his animal anatomy studies, which are fundamental for understanding animal wellbeing.

At 6 pm, move into the Great Hall for an exciting talk by the star of ‘Trust Me I’m A Vet’, Judy Puddifoot, who will be discussing the work behind the scenes of the programme, in particular her work with dogs, guinea pigs and tortoises!

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Judy Puddifoot on Trust Me I’m a Vet. ©BBC Two

Throughout the college you will find stands dedicated to different professions who care for animal wellbeing, including staff from our Hertfordshire Queen Mother Animal hospital talking about how your dog could save lives by giving blood. Check out visiting animal charities and community teams to see how their work with animals benefits both human and animal wellbeing. For instance, hear about how dogs are trained to become assistance animals, from The Dogs for Good team. Try on surgical gowns and develop your clinical skills in our mock clinic area; our neighbours the Beaumont Sainsbury Animal Hospital will be showcasing their accredited dog and cat waiting rooms, complete with research-approved classical music for the cats!

At 7 pm, get ready for a dissection conducted by the Head of Anatomy services, Andrew Crook MBE. He can assure you that “this will be a fantastic opportunity to witness a real dissection and learn about anatomical structures first hand.” You can either watch the dissection first hand (max 100 spaces in the theatre, first come first served), or if you prefer, the whole thing will be being live streamed to the Great Hall lecture theatre, for you to watch the process without the olfactory component.

Dissection

©Royal Vet College

By taking part in our activities you can learn about the world–class science being produced by our researchers, including ferret preferences and how fractures relate to neurobiology. Postdoctoral Researcher Dr Rowena Packer and her team will be talking about stress levels in Border Collie dogs, how it is affected by neurological disorders, and how they can measure it. You will find out how this cutting-edge research will benefit the wellbeing of dogs with epilepsy!

Manager of the Grant Museum of Zoology and author Jack Ashby is also joining us with his new book – Animal Kingdom: A Natural History in 100 Objects.

You’ll have to try and remember all you heard about throughout the evening, because our student bar will be hosting a Pub Quiz. Time to use your new animal knowledge to win prizes!


Night at the Vet College is on November 22nd, 5.30-10pm, at the Royal Veterinary College’s Camden Campus: 4 Royal College Street, NW1 0TU (10 mins walk from Kings Cross, Mornington Crescent or Camden Town tube stations). You can book your free place here, however there is limited capacity so early booking is encouraged: https://www.eventbrite.co.uk/e/night-at-the-vet-college-wellbeing-tickets-38770001117

Stress and the gut – it’s not all in your mind (Part 2)

By Kim E. Barrett, Division of Gastroenterology, Department of Medicine, University of California, San Diego, USA, @Jphysiol_eic.

This article originally appeared in our magazine, Physiology News.

The numerous microbes living inside of us help break down nutrients and “educate” our immune system to fight infection, but how do they help us respond to stress?

The microbiota as a mediator of responses to stress

Gut microbes change when people have intestinal diseases, such as inflammatory bowel diseases and irritable bowel syndrome. Indeed, some of the characteristics of these diseases can be transferred to animals in the lab that lack microbes, using microbes from diseased mice or humans. It is also becoming increasingly clear that gut microbes and their products may have effects well beyond the confines of the intestine itself.

Perhaps the most intriguing aspects of this area of research is that which ties the composition of the gut microbiome to brain function and the brain’s response to stress. Further, the adverse effects of stressful situations on gut function depend on the presence of intestinal microbes. To date, research supports bi-directional communication between the gut and brain (pictured below) that influences the normal function of both bowel and brain alike. This may explain, for example, why some digestive and psychiatric disorders go hand-in-hand (Gareau, 2016).

gut brain

Bi-directional communication between the gut and brain.

Evidence in human patients largely shows correlation not causation so far. Still, it is intriguing to observe that derangements in the microbiome have been associated with many conditions, including depression, autism, schizophrenia and perhaps even Parkinson’s disease (Dinan & Cryan, 2017).

Therapeutic manipulation of the microbiota – from probiotics to transplants

So if both intestinal and neuropsychiatric conditions are potentially caused by changes in the gut microbes (at least in part), and if such alterations also mediate the impact of stress on the relevant organ systems, can we mitigate these outcomes by targeting the microbiota?

Several approaches have been posited to have either positive or negative effects on the make-up of the gut microbiota and its intestinal and extra-intestinal influences.  Perhaps the most obvious of these is the diet. While the gut microbiota was at one time felt to be relatively immutable in adulthood, improved  techniques indicate that its make-up, in fact, is profoundly influenced by the composition of the diet and even by the timing of meals. For example, Western diets, high in meat and fat, decrease the diversity of the microbiota (and may even promote the emergence of pathogenic properties in commensals), whereas diets rich in plant-based fibre increase it.

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Another approach to targeting the microbiota is the use of antibiotics, although for the reasons discussed in Part 1, these are likely to be mainly deleterious, particularly early in life. The composition of the microbiota can also be altered directly by the administration of probiotics, which are commensal microorganisms (the host benefits, while the microbes are unaffected) selected for their apparent health benefits that can be taken orally.  Studies in animal models demonstrate that probiotics can improve both gut and cognitive function in animals exposed to a variety of stressors, or can negate the cognitive dysfunction accompanying intestinal inflammation or infection.  However, not all probiotics are created equal, and much work remains to be done both to validate animal studies in human clinical trials, and to define characteristics of probiotic strains that predict efficacy in a given clinical setting.

Perhaps the approach to targeting the microbiota that has attracted the most recent public attention is the practice known as faecal microbial transplant (FMT), where faecal material is transferred from a healthy donor (often a relative) to someone suffering from a specific intestinal or extraintestinal disease.  Enthusiasm for FMT derived initially from its dramatic efficacy in some patients suffering from disabling and persistent diarrheal disease as well as other symptoms associated with treatment-resistant infections by C. diff (a harmful bacteria).  More recently, there have been encouraging data suggesting that FMT may be effective in producing remission in inflammatory bowel disease, although the long-term consequences are unknown, and larger, well-controlled studies are needed.  Exploratory reports even suggest beneficial effects of FMT on gastrointestinal and behavioural symptoms of autism, or in obesity and metabolic syndrome (a cluster of conditions that occur together and increase your risk of heart disease, stroke and other conditions), but much further work is needed to validate these preliminary data.  Ideally, FMT procedures should be conducted under carefully-controlled and physician-supervised conditions to screen for the potential presence of pathogens or toxins.  Nevertheless, despite the obvious “yuck” factor, “do-it-yourself” instructions can readily be found online (there are even Facebook groups), and some individuals are sufficiently distressed by their condition to give it a try.

faecal_transplant_pill

Yep, this is exactly what you think it is.

Mitigating negative effects of stress

In conclusion, it is clear that our response to stress, whether manifested in our thought patterns or in our gut, is dramatically shaped by the microbiota that resides in the intestines.  Particularly in humans, studies conducted to date have largely been confined to cataloguing the key players in a given setting, but animal data are provocative, and studies focusing on microbes’ roles and functions in humans will doubtless follow.   No matter what, in the coming years, the explosive growth of studies aiming to target the microbiota for health benefits should give us a much better understanding of which approach, if any, is likely to be most beneficial for a given condition and even a given individual, since host factors clearly can also impact our microbial composition.  This work holds the promise of ameliorating negative effects of stress, and perhaps may offer new avenues for the therapy or even prevention of the myriad of stress-related disease states that are increasing in incidence in developed countries.


References

Dinan TG & Cryan JF. (2017). Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. The Journal of physiology 595, 489-503.

Gareau MG. (2016). Cognitive function and the microbiome. International Review of Neurobiology 131, 227-246.

 

Stress and the gut – it’s not all in your mind (Part 1)

By Kim E. Barrett, Division of Gastroenterology, Department of Medicine, University of California, San Diego, USA, @Jphysiol_eic.

This article originally appeared in our magazine, Physiology News.

We all know that stress has an impact on the function of our digestive system. Whether it is the transient butterflies that accompany an exam or an interview, or the more toxic consequences of chronic stress, our experience of our world and its challenges can profoundly alter our digestion, absorption of nutrients, and excretion.

What has been less fully appreciated, until recently, is that communication between the brain and gut is bi-directional. Gut illnesses may be accompanied by brain disorders, such as anxiety, depression, and memory problems.  The brain and spinal cord are in constant communication with the gut, in part via the “little brain” – the nerves present in the gut that communicate with the brain.

While we humans like to think that we are masters of our own universe, in fact we, along with all other beings, are superorganisms. Our bodies consist not only of our own cells and genome, but also of distinctive populations of ‘friendly microbes’, along with their genes and ability to break down compounds. This so-called “microbiome” is made up mostly of bacteria, the best-studied populations, but also other microbes such as fungi and viruses (which are only now beginning to be examined).  Specialized groups of microbes inhabit various parts of our body, such as the intestines, mouth, skin, lungs, and genitals. The most extensively characterized of these microbiomes is the collection of bacteria in the gut, consisting of thousands of species in a typical healthy human adult. They reside throughout the intestines, but are most heavily concentrated in the colon. There are as many as 1014 of them throughout the gut. That’s ten times the number of human cells in the entire body (Sekirov et al., 2010). Recently, the 10:1 ratio has been disputed, with a claim that the numbers of human cells and gut bacteria are of the same order of magnitude (Sender et al., 2016). Even if this true, the microbes collectively have more genes than our cells do.

We are rapidly learning the ways in which these gut microbes may be important mediators of the cross-talk between the gut and brain. They are, in turn, influenced by environmental conditions, such as stress and diet, in ways that change their impact on both our thinking and digestion.

gut brain

 

Friendly microbes – what do they do for us?

Microbes, in the gut or elsewhere, are not essential for life, as illustrated by the ability to raise animals in a sterile environment in the lab. Nevertheless, the gut microbes in particular offer several advantages to the organism they inhabit. For us, they break down nutrients we can’t, such as dietary fibre, drugs, carcinogens, and compounds that break down into vitamins.  Similarly, the microbiota “educate” the immune system of organs such as our lungs and intestines to fight foreign substances but tolerate the proteins of broken-down food or other harmless microbes.

The organisms of the microbiome also defend against pathogens by crowding them out, producing substances that kill bacteria or keep them from reproducing, or causing the host to create those lethal compounds itself. For this reason, antibiotics that kill beneficial microbes can render patients susceptible to intestinal infections and overgrowth of harmful bacteria, such as Clostridium difficile (C. diff).

gut brain 2

3D cellular model of an intestine by Ben Mellows, PhD Student, University of Reading, UK

Gut microbes and birth

We think that gut microbes exist in the body immediately after birth, although some controversial data suggests the presence of microbes in the fetus before birth. Animals without microbes can be born via Caesarean section (C-section), implying that even if there are microbes in the womb, organisms don’t need them to survive (Perez-Munoz et al., 2017).

For babies delivered vaginally, their gut microbes are initially very similar to the mother’s vaginal microbiota, whereas they differ substantially for babies delivered by C-section. An intriguing recent study partially restored “normal” microbes in the gut, mouth, and skin by exposing babies delivered via C-section to the mother’s vaginal fluids. The authors thought that this might reverse the known association between C-section deliveries and an increased risk for immune and metabolic disorders (Dominguez-Bello et al., 2016).

For the first year or two of life, the baby’s microbes are relatively simple and variable, but they gradually take on the characteristics of a mature, adult-like microbiome. These early years are also a critical period for maturation of the immune system, so it makes sense that disrupting the maturation of the infant’s microbes also predisposes them to autoimmune and allergic diseases. For example, the increasing tendency to protect babies from germs or an excessive early-life use of antibiotics may set them up for an increased later risk of asthma, metabolic disease or obesity. This is called the “hygiene hypothesis” (Schulfer & Blaser, 2015).

Stay tuned for the part 2 of the series next week to learn about how gut microbes respond to stress, and the efficacy of therapeutics, from probiotics to transplants.


References

Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, Bokulich NA, Song SJ, Hoashi M, Rivera-Vinas JI, Mendez K, Knight R & Clemente JC. (2016). Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med 22, 250-253.

Perez-Munoz ME, Arrieta MC, Ramer-Tait AE & Walter J. (2017). A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 5, 48.

Schulfer A & Blaser MJ. (2015). Risks of antibiotic exposures early in life on the developing microbiome. PLoS Pathog 11, e1004903.

Sekirov I, Russell SL, Antunes LC & Finlay BB. (2010). Gut microbiota in health and disease. Physiological reviews 90, 859-904.

Making sense of stress in the wild

By Kimberley Bennett, Abertay University

Imagine leaning forward over the edge of a precipice. Lurching back to safety, you picture the forest hundreds of metres below. Is your heart racing? Are your palms sweating? Our body’s stress response to an ever-changing environment enables us to survive and flourish.

Physiologists play a crucial role in developing our understanding of the mechanisms involved. To highlight the exciting work that they do, our 2017 theme is ‘Making Sense of Stress’. Follow the conversation on Twitter using #YearOfStress.

Launching the theme will be Dr Kimberley Bennett’s talk, ‘Making sense of stress in the wild’, at the Association for Science Education’s (ASE’s) Annual Conference on 6 January 2017. Read a teaser to her talk below!

Coping with stress is a major issue in modern society, but it’s easy to forget that wildlife experiences stress too. Without enough water, plants wilt and die and whole crops fail; without the right habitat, a small population of rare animals dwindles and dies out, causing extinction of the species; a whole coral reef bleaches when the water temperature gets too high, causing catastrophe for the ecosystem, and massively increasing flooding risk for people living by the coast. We really need to pay attention to stress in the wild because the consequences can herald disaster.

Stress is the biological response to a major challenge, whether it’s at the whole organism or cell level. A gazelle in the Serengeti chased by a lion experiences the same stress responses that we do – a surge of adrenaline and cortisol that cause increased heart rate and blood pressure and a release of glucose. These changes make sure there is enough fuel and oxygen to cope with increased demand at the tissue and cell levels. Sudden change or mismatch in the supply of oxygen and fuel leads to increased production of reactive molecules called ‘free radicals’ that can damage cells. If the temperature gets too hot too fast or if the acidity of the cell changes too much, proteins (the molecules that catalyse reactions, transport substances and provide structure) can fall apart or unravel. So cells have to increase their defence mechanisms too. Cellular defences include antioxidants that mop up the free radicals, and heat shock proteins, which refold damaged proteins and stop them forming a sticky mess inside the cell.

The old adage that what doesn’t kill you makes you stronger is often true: short term ‘good stress’ builds up these defences and makes organisms better able to deal with stress later on. However, sometimes defences can be overwhelmed or can’t be maintained for long periods. The organism then experiences the same sorts of problems as people under chronic stress: lower immunity, altered metabolism, anxiety and tissue damage (like ulcers). In wildlife, this can have major consequences for breeding success or even survival. By affecting whether organisms survive and thrive, stress dictates which individuals contribute to the next generation. Stress shapes population dynamics, lifestyle and adaptations, and is therefore a powerful agent of natural selection.

kb-fieldwork

I work on seals, top marine predators that are used to stress as a normal part of their existence. Their individual and population level health is an indicator of ecosystem health. Seals are air breathing mammals that feed underwater, but need to come to the surface to breathe, and to come ashore to rest, breed and moult. Diving on a single breath hold means they need to conserve oxygen; to do this, blood flow is restricted mostly to the heart and brain, so that other tissues may experience free radical production while oxygen levels are low. On land, seals need to fast, often while they are doing energy-demanding activities i.e. shedding and replacing hair, producing milk, defending pups or territory, or undergoing rapid development. Injury and infection can occur from skirmishes or trampling. Seals may have to reduce their defences to deal with all these demands on their energy when food is not available. In addition to their ‘lifestyle stressors’, seals face stress from competition for access to fish, disturbance on haul out or displacement from foraging grounds as a result of human activity, and the accumulation of contaminants in their blubber.

We need to understand natural and man-made causes of stress in wild populations, distinguish good stress from bad stress, and understand how multiple stressors at the same time can create problems. That means we have to have effective tools to measure stress and its consequences in organisms that can’t tell us how they feel. But can we measure stress responses in wildlife? What do they mean in context? And can they help in managing stress in the wild?

I will address all these questions and more at the ASE’s Annual Conference on Friday 6 January 2017, as part of the annual Biology in the Real World (#BitRW) lecture series. Please drop by the Knight Building, LT 135, at the University of Reading, at 1.30pm to find out more!

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