Author Archives: The Physiological Society

About The Physiological Society

The Physiological Society brings together over 3,500 scientists from over 60 countries. Since its foundation in 1876, its Members have made significant contributions to our knowledge of biological systems and the treatment of disease. We promote physiology and support those working in the field by organising world-class scientific meetings, offering grants for research, collaboration and international travel, and by publishing the latest developments in our leading scientific journals, The Journal of Physiology, Experimental Physiology and Physiological Reports.

11 networking tips to boost your career

by Hannah Marie Kirton, Faculty of Biological Sciences, University of Leeds, UK

We hear it all the time: networking is so important for us. It’s true! Never underestimate the power of networking. However, for some of us, it’s not that easy. Do you find it daunting? Difficult to initiate? Or do you just need a motivational boost to start building new and existing relationships? Amidst the inhibitions to just get out there and network, it’s important to realise the true potential of networking and how it impacts career success. In this article, I have compiled a ‘Mini Journal’ of networking tips and advice, but more importantly, explained its importance.

What is networking?

Networking is an interaction that exchanges information and ideas, in order to develop productive and professional relationships. Networking is best, and easiest, at conferences and meetings, where there are a multitude of professionals in and related to your field of interest. But remember, networking is not just about speaking with key leaders in your field. It’s also just as important to talk and network with PhD students, postdocs and other early career researchers. If anything, forming new contacts with early career researchers is more beneficial, since you will grow together in your field and may regularly contact each other throughout. Plus, they are a direct contact to the group leaders who you may be interested in working with and therefore, a good way to understand how that lab or institute works and supports early career researchers.

AGM 2017

Why is networking important?

Put simply, networking with PhD students, postdocs and group leaders can benefit both your research and recognition, which, if performed correctly, will boost your career.

  • Research

Communicating with researchers and experts in your field can open up new questions and ideas for your research. This will enable you to view your research from a different point of view, both technically and theoretically. Collectively, this helps to shape and strengthen your research. This also forms the basis of collaborations, which generates a multidisciplinary approach to research and facilitates publications in high-impact journals.

  • Recognition

Networking is also an excellent platform to increase visibility within your research field, and visibility to prospective future employers. It also enables you to communicate with PhDs and postdocs you may later work with, who are equally key to your future.

How to network?

Try to break away from your comfort zone at conferences and meetings. It is so easy to stick to your lab team and supervisor, but remember, you have already formed professional relationships with them and see them every day! Challenge yourself. Be curious and open your mind.

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Beginners top tips

  • If networking is not your strongpoint, start by speaking to early career researchers in your field. Attend early career breakout meetings such as the postgrad, postdoc breakfasts and career sessions, and talk to the people around you, i.e. talk about their poster and research, or even their career. It’s amazing how quickly people let their guard down once you talk about or compliment their research.
  • Attend poster sessions. These are generally more informal and relaxed, helping you to ask your question and engage in conversation over research.
  • Add your e-mail address to your posters. This will help people to get in touch with you. Remember, you are not the only one networking.
  • Simple ways to interact with researchers at conferences can include striking a friendly conversation at a dinner or coffee queue or sitting next to someone at lunch. This is an easy way to build your confidence and get used to introducing yourself at conferences.
  • Alternatively, utilising a familiar point of reference helps to build relationships, i.e. mentioning a work colleague you both know.
  • If you’re not ready to ask a question at the end of oral presentations, approach the presenter after the session. Be confident, but think carefully about your question!

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Advanced top tips

  • If you aim to speak with team leaders in your field and don’t quite have the courage to walk over and introduce yourself, look out for them at the conference reception or dinner. An easy icebreaker is to smile, introduce yourself, and talk about your lab and research. Try to follow that up with an easy question about their research, or yours!
  • Be specific when you approach people. If you admire their work then demonstrate it, by saying something like: ‘I really enjoyed your recent paper in Neuron about sodium channels’.
  • If there is a particular person you would like to speak with, email them a few days before the conference and let them know you’d like to meet up. This cuts out any awkward introductions, and forces you to follow your plans to meet.
  • Alternatively, plan ahead prior to a conference or meeting. Read about their research and publications before approaching them with your questions. This will help you articulate questions specifically, clearly and with confidence.
  • Once you have developed a network, make a strong effort to maintain that link. Promptly reply to emails or make regular contact when possible. It is very hard to make connections, but very easy to lose them.

Exercise now, thank yourself later

by Glenn Wadley, Associate Professor, Institute for Physical Activity and Nutrition (IPAN), Deakin University, Australia.

Endurance exercise and healthy hearts

A wealth of evidence shows that physical activity helps prevent heart disease and all causes of mortality (1) and has benefits for the heart at any age (2): aerobic exercise – often referred to as ‘cardio’ – and in particular endurance-training, is beneficial to the heart. But these effects – in adults – are only temporary and lost soon after training is stopped (3-5). Because of this, it has been assumed until now that the beneficial effects of exercise for the heart are also temporary for young and adolescent mammals, including humans.

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The athlete’s heart – when big is beautiful

Moderate levels of endurance exercise training improve the structure and function of the heart, and makes it grow larger, resulting in what is called athlete’s heart, or physiological cardiac hypertrophy (3-5). This larger heart is beneficial and quite distinct from the enlarged hearts observed in disease, which display reduced function, and increased scarring and molecular and structural differences, in addition to heart failure and increased mortality (6). In contrast, athlete’s heart can improve quality of life, since people with a physiologically healthy, bigger heart will pump more blood and thus can train harder at any given age (7). This effect is of particular benefit as adults get older.

The workhorse cells of the body – cardiomyocytes

 In the heart, specialised muscle cells do the heavy lifting: they are called cardiomyocytes, and are highly resistant to fatigue. The adult human heart contains several billion cardiomyocytes and their coordinated contraction produces around 100,000 heartbeats per day, every day.

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Cardiomyocytes up close.

Until recently, we thought that the number of cardiomyocytes in mammals’ hearts was fixed shortly after birth. Adult cardiomyocytes don’t get renewed or multiply much, so we thought that the heart grew larger in response to training because the existing cardiomyocytes grew larger, rather than because there were more of them.

However, our recent study has established that an increase in cell number also plays a considerable role in cardiac growth in response to just four weeks of moderate intensity exercise, if the training is conducted during juvenile life, which is 5-9 weeks of age for a rat. This training period would be equivalent to late childhood and puberty in humans. We also found that this effect of exercise on cell number diminishes with age and is lost by adulthood. Indeed, when the same exercise training program is conducted in adolescent rats (11-15 weeks of age, or around the time of late puberty and reproductive maturation in humans), there is a much smaller impact on cardiomyocytes multiplying. In adult rats, heart mass and cardiomyocyte size still increase following exercise training, but without any increase in cardiomyocyte number. Clearly, endurance exercise is beneficial for the heart at any age, but it appears that a window of time exists in the younger heart whereby exercise might be able to grow more cardiomyocytes.

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With regards to the benefits of juvenile exercise for the heart, perhaps the most compelling finding is that the increased heart mass and around 40% increase in cardiomyocyte number remain well into adulthood. What’s more, this increase in cell number is sustained despite the rats being couch potatoes for a prolonged period of time – the equivalent of 10 years in humans! Having more cardiomyocytes potentially makes the heart better equipped for the structural and functional challenges of adult life. For example, in the UK, the 915,000 survivors of heart attack (8) are left with a heart containing up to 25% fewer cardiomyocytes (9) that are not replaced, along with a large degree of scarring and fibrosis. Thus, having more cardiomyocytes saved up for a rainy day could be a handy reserve if you are unfortunate to suffer a cardiac event.

There are already plenty of good reasons to exercise regularly and we know exercise is beneficial for heart health at any stage of life. However, should these recent findings translate to humans they would provide a new reason to ensure there are sufficient opportunities for children to engage in regular physical activity in school curricula. Importantly, our research suggests that there may be long-term cardiac benefits of physical activity for all children, even if the children do not continue with regular exercise in adulthood. Unfortunately, we know the majority of children do not meet physical activity recommendations (10) and therefore their hearts may be missing out on the best start to life.

References:

  1. G. Erikssen, Sports medicine (Auckland, N.Z), 2001, 31, 571-576.
  2. S. Lachman, S. M. Boekholdt, R. N. Luben, S. J. Sharp, S. Brage, K. T. Khaw, R. J. Peters and N. J. Wareham, Eur J Prev Cardiol, 2017, DOI: 10.1177/2047487317737628.
  3. O. J. Kemi, P. M. Haram, U. Wisloff and O. Ellingsen, Circulation, 2004, 109, 2897-2904.
  4. R. C. Hickson, G. T. Hammons and J. O. Holloszy, Am J Physiol, 1979, 236, H268-272.
  5. D. S. Bocalini, E. V. Carvalho, A. F. de Sousa, R. F. Levy and P. J. Tucci, Eur J Appl Physiol, 2010, 109, 909-914.
  6. B. C. Bernardo and J. R. McMullen, Cardiology clinics, 2016, 34, 515-530.
  7. R. J. Shephard, British journal of sports medicine, 1996, 30, 5-10.
  8. British Heart Foundation, BHF CVD Statistics Factsheet – UK, https://www.bhf.org.uk/statistics
  9. M. A. Laflamme and C. E. Murry, Nature, 2011, 473, 326-335.
  10. Australian Bureau of Statistics, Australian Health Survey: Physical Activity, 2011-12. 2013. http://www.abs.gov.au/AUSSTATS

 

Forging links between the scientific community and the devolved nations

by Henry Lovett, Policy & Public Affairs Officer

Politics does not only happen in Westminster. The United Kingdom of Great Britain and Northern Ireland has a complex system of internal devolution, with Parliaments or Assemblies in Belfast, Cardiff and Edinburgh, as well as London. The Physiological Society is always keen to engage with the devolved administrations to discuss local industries and university research specialities, as well as the impact of their unique local political situation on UK-wide concerns such as the Industrial Strategy. Our policy team has just come back from Edinburgh, where Science and the Parliament 2017 was taking place in the city’s impressive science centre, Dynamic Earth.

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Talks being given at the Welsh Assembly for “Science and the Assembly”

The theme of Science and the Parliament was “Science, Innovation and the Economy”, but of course this was broadened in everyone’s mind to include Brexit. The UK government has claimed that science, technology, and innovation will be at the heart of our post-Brexit economy, and the discussion centred on what this means for Scotland (an area that voted to remain in the EU, which was also a big issue in the Scottish Independence referendum). Despite being a hotbed of commercialisation of university-derived research, there was much discussion about how to improve the progress of start-up companies in Scotland. They take longer to reach a turnover of £1m than anywhere else in the UK or most of Europe. It was felt that the new structures around research and innovation funding, UK Research and Innovation, need to include significant representation from Scotland (and the other devolved nations) not to become too England-centric. There was also general concern that fundamentals such as infrastructure and connectivity affect start-up companies, so investment has to be made to make areas of Scotland attractive places to base a company.

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Physiological Society Members who visited our stand at “Science and the Parliament” in Edinburgh

Earlier in the year we also attended Science and the Assembly in Cardiff, and Science and Stormont in Belfast. Each of these events has a slightly different take on how to explore science in the local area. Cardiff focused on antimicrobial research, while Belfast titled their event “Skills for Science and Innovation”. The research discussed in Cardiff was very impressive, both from local universities and companies based in the area. The talks in Belfast had a much more political focus, with concerns being raised about the effects of the ongoing suspension of the Northern Irish Assembly. This was halting new initiatives, including those designed to address the serious problem of the supply of science teachers in Northern Ireland.

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Society Members who visited our stand at “Science and Stormont” in Belfast

At each of these events we were delighted to have an exhibition stand to raise the profile of physiology and increase recognition of the policy work we are undertaking. These events present great opportunities to mingle with people involved locally in scientific research and outreach, in order to discuss everyone’s projects and initiatives. We were pleased to also welcome Physiological Society members based locally to discuss our policy work with them, find out their views and concerns for The Society to address, and generally catch up about the exciting physiology research being done across the UK.

Thanks are due to all the Members who visited us, all the politicians who attended and spoke at the events, and the Royal Society of Chemistry for arranging these valuable opportunities to connect with politicians and scientists across the UK.

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.

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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).

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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.

Guardians of the brain under pressure

By Sevda Boyanova, @boyanova_sand Hao Wang, @olivia_hao, King’s College London, UK

In England, more than 1 in 4 adults are affected by high blood pressure, making it the third most common cause of premature death, after smoking and poor diet. Globally, 1.5 billion people are expected to have high blood pressure by 2025. This ‘silent killer’ usually occurs without symptoms, and contributes to more than half of heart attacks and strokes.

hypertension

Recently, scientists have revealed a connection between high blood pressure and the disruption of the gateway to the brain’s blood circulation, called the blood-brain barrier. These disruptions might lead to problems in the part of our nervous system involved in heart rate and blood pressure regulation (called the autonomic nervous system), thus contributing to high blood pressure.

So, how exactly does the blood-brain barrier work? The blood-brain barrier is the boundary between the blood flow that is circulating around our body, and the brain. Its function is two-fold: it regulates the balance of molecules flowing in and out of the brain, and also protects the brain from toxic substances. It’s formed by the cells that make up the walls of capillaries, tiny blood vessels in the brain. These cells, called endothelial cells, are joined together tightly so that blood contents cannot cross into the brain like they do in other parts of the body. The cells of the brain capillaries also contain transporters which move specific molecules across the walls of the capillaries. Surrounding the capillaries are three types of cells – astrocytes, pericytes and microglia – which work together with them to maintain a stable blood composition, allowing the brain to function properly. Scientists have implicated three players in the link between the blood-brain barrier and high blood pressure.

Blood Brain Barrier

This cake, submitted to our #BioBakes competition, represents the blood-brain barrier, with the cells of the blood vessel wall (blue) tightly joined by adhesive molecules (green squares) so that potentially harmful components in the blood cannot cross.

The first is a molecule involved in increasing blood pressure by constricting blood vessels (called angiotensin II). Angiotensin II can make the blood-brain barrier more porous which may affect the nervous system’s control of blood pressure. However, at the moment it is not clear if blood-brain barrier disruptions happen prior to or as a result of high blood pressure.

The second is molecules involved in the immune response. High blood pressure is related to low levels of inflammation (the first response when a threat to the body is detected), which is enough to activate the immune system. This activation leads to more inflammatory cells and molecules in the blood. These molecules can affect the structure of the blood-brain barrier, weakening it. Researchers have shown an increase in molecules that take part in the inflammatory response and in the production of white blood cells, during high blood pressure and heart failure. Therefore, these factors may play a part in the initial dysfunction in the blood-brain barrier, and may work alongside angiotensin II to worsen the disease.

The final player comes from the brain itself, in the form of cells that mediate inflammation. These are some of the brain cells that aren’t neurons, called astrocytes and microglia. These cells are normally involved in maintenance, surveillance and repair of the brain. However, researchers have found that microglia might be responsible for sustaining high blood pressure and astrocytes might work together with the microglia to release inflammatory molecules in response to infection by bacteria or viruses. Therefore, glial cells might have an effect on the blood-brain barrier’s ability to keep harmful molecules out. Also, there is evidence that glia could influence the activity of the autonomic nervous system (involved in heart rate and blood pressure regulation); in animal models, increased glial activation happens in brain regions important for the control of blood pressure.

The growing area of research on the link between the blood-brain barrier and high blood pressure is exciting because the blood-brain barrier is a very important target for new therapeutics. Further investigation of the mechanisms involved in maintaining the integrity of the blood-brain barrier will be useful for developing interventions targeted at treating or limiting the progression of conditions such as high blood pressure.


Reference:

Setiadi, A. et al., 2017. The role of the blood-brain barrier in hypertension. Experimental Physiology.