GAtherton

The importance of microbiomes

[et_pb_section fb_built="1" admin_label="section" _builder_version="4.16" global_colors_info="{}" theme_builder_area="post_content"][et_pb_row admin_label="row" _builder_version="4.16" background_size="initial" background_position="top_left" background_repeat="repeat" global_colors_info="{}" theme_builder_area="post_content" custom_margin="11px|auto|11px|auto|true|false"][et_pb_column type="4_4" _builder_version="4.16" custom_padding="|||" global_colors_info="{}" custom_padding__hover="|||" theme_builder_area="post_content"][et_pb_text admin_label="Text" _builder_version="4.16" background_size="initial" background_position="top_left" background_repeat="repeat" global_colors_info="{}" theme_builder_area="post_content"]Microbiomes are all the microorganisms (bacteria, fungi, viruses etc.) that are present in a particular area in the body. These are found in places such as the gut, lungs and mouth and microbiomes in different areas are made up of a different distribution of species. They are beneficial to our bodies and influence a wide range of things such as our immune system, mental health and respiratory health. In the average healthy person, these different species exist in a regulated balance to perform various functions and confer health benefits - they provide nutrients that we cannot make ourselves. An imbalance (called dysbiosis) between the species of microorganisms present is heavily associated with disease.

See more about microbiomes on this page - https://aspergillosis.org/the-host-its-microbiome-and-their-aspergillosis/?highlight=microbiomes

The gut microbiome – mental health & the immune system

The most well-studied microbiome is that of the gut. In the gut there are about 100 trillion (100 000 000 000 000!) bacteria of around 1000 different species. These bacteria can communicate with the brain via something called the microbiota-gut-brain axis, which describes a two-way interaction between the brain and the gut. The gut is able to send messages to the brain in the form of chemicals (called neurotransmitters) which travel along nerves and through the bloodstream to reach the brain where they have various effects. These neurotransmitters are produced by bacteria that live within the gut.

The gut microbiome is a regulator of stress and anxiety levels and has a strong influence on mood and depression. This has been demonstrated through several studies. For example, mice studies have shown that those who don’t have a gut microbiome (called germ-free mice) have an abnormally strong stress response in comparison to mice that have a gut microbiome[1]. Interestingly, this heightened response was reduced after the addition of a resident gut bacteria called Bifidobacterium. This species, along with another key species called Lactobacillus, has been shown to significantly reduce anxiety in humans[2]. Faecal microbiota transplantation (FMT) is a process where faeces from a healthy donor are transplanted into a recipient to restore the balance of bacteria in their gut. FMT experiments were performed from healthy patients to those with depressive and anxiety-like symptoms and vice versa; in every case, ill patients reported a reduction in symptoms after receiving the transplantation and healthy patients reported an increase in symptoms[3]. Finally, serotonin is a hormone that acts in the brain to cause positive and happy moods. This hormone is produced by gut bacteria and, in fact, about 90% of the body’s serotonin is made by these bacteria[4]. These are just a few examples that demonstrate the impacts that gut bacteria have on mental health.

To read more about the impact of the gut microbiome on mental health, check out this article by the BBC - https://bbc.in/3npHwet

Our immune system (i.e. the system that helps us fight off infection) is also affected by the gut microbiome. Various gut bacteria are able to stimulate immune cells (T cells) to specialise into a specific type of cell called T regulatory cells (or Tregs). Tregs suppress the immune system and hence exaggerated allergic reactions (e.g. eczema) can develop from decreased activation of these immune cells. In the gut, some bacteria are capable of activating Tregs. This suggests the possibility of administering these species to patients with over-active allergic responses to help ease allergy and inflammation. This hypothesis is yielding initial results that are encouraging, for example in eczema, https://nationaleczema.org/topical-microbiome/. Also see the section at the end on probiotics.

Lung & gut microbiomes – allergy and asthma

The lower airways are home to a different population of microorganisms – called the lung microbiome. The makeup of this microbiome is different to that of the gut. There are far less bacteria present in the lungs compared to the gut and this environment is much harder to study, mainly because methods of obtaining lung samples are invasive. It was initially believed that the lungs were a sterile environment containing no bacteria and the lung microbiome was not discovered until recent years, therefore, much less is known about this population compared to the gut.

What is known is that the lung microbiome does play a role in respiratory health and a reduced diversity of microbe species is associated with disease – with more reduction in diversity being associated with more severe disease. Importantly, the lung microbiome is connected to the gut microbiome through the lung-gut axis and respiratory and gastrointestinal diseases are often present together. The two are linked through the immune system and communication occurs, as with the gut and the brain, through chemical messengers. This means that changes in the gut microbiome seem to have an effect on airway allergic responses and asthma as well. Several studies have shown that asthmatic patients have an altered range of species in their lung and gut microbiomes compared to a non-asthmatic person, and this imbalance is thought to contribute to the hypersensitivity and hyperreactivity of the immune system.

One bacterial species called Bacteroides fragilis (B. fragilis) has been shown in experimental mouse models (intended to simulate asthma) to regulate the balance between the type of immune response that the body produces[5]. Allergic inflammatory responses are produced by a specific pathway (called the Th2 pathway) whilst non-allergic immune responses are produced by a different pathway (Th1). This species of bacteria is important because it controls the balance between these two pathways to ensure that neither of the responses become dominant. B. fragilis relies on a carbohydrate called N-glycan and N-glycan production is reduced in patients with severe asthma[6]. This makes it harder for B.fragilis to grow so it is more likely that an allergic (Th2) response could dominate as the balance between the two pathways becomes less regulated. This is one example of how important gut bacteria can be in a disease like allergic asthma.

Click this link to read more about the gut-lung connection and its relevance in COVID-19 - https://bit.ly/3FooPOp

The future – probiotics, FMT and research

Probiotics are defined as ‘live microorganisms which when administered in adequate amounts confer a health benefit on the host (person)’. They come in different forms and are taken for various health benefits, with different ones having different compositions of bacteria.

Probiotics have been studied in recent years for use in asthmatic patients with allergic sensitisation. Some experiments have been done to test probiotics as a treatment for asthma and have proved to be successful. For example, one study gave probiotics to 160 asthmatic children aged 6-18 as capsules for 3 months; the results showed that the patients had lowered asthmatic severity, improved asthma control, increased peak expiratory flow rate and decreased IgE (a marker of allergy) levels[7]. Notably, lots of the studies done on this topic have been in mice or children and the results are inconsistent, so more research is needed in this area before probiotics can be recommended as a treatment.

FMT is an established effective treatment for Clostridium difficile infections, but experiments have not yet been fully studied in allergic diseases. There is currently an ongoing clinical trial for oral encapsulated FMT in the treatment of peanut allergy and phase I was completed but results have not yet been published. As these trials become more numerous, it is likely that they will extend to allergic asthma and possibly even allergic Aspergillus-sensitisation. As it stands, there is some resistance to such trials as some people are opposed to, or ‘grossed out’ by, the idea of transferring stool from one person to another. However, in reality, FMT is not a transplant of faeces, but of microbiota from the intestines. Furthermore, not all FMT trials have had positive outcomes – a trial in haematopoietic stem cell transplant patients proved to be fatal for one man who received a donor sample that hadn’t been screened for a drug-resistant type of E.coli [8]. FMT research for allergy is still in early stages and more research is needed to ensure its safety, but there is no doubting it has great potential for the future.

Nevertheless, maintaining a healthy balance of bacteria in your gut and lung microbiomes is important for everyone’s health and wellbeing. This is helped by having a healthy balanced diet containing lots of fibre and eating foods that contain lots of beneficial bacteria like natural yoghurt or kefir. Although they are not formerly recommended as treatment by the NHS, you may want to consider taking a probiotic. However, you should be aware that probiotics are considered dietary supplements as opposed to medication and so the manufacturing of these products is not regulated, meaning you cannot be certain that they contain the bacteria stated on the label. It is also worth noting that probiotics used in clinical trials are likely to be more effective than ones that can be bought over the counter as they probably contain a higher dose and more species.

There is good evidence that taking a probiotic whilst on antibiotics is effective at reducing antibiotic-associated diarrhoea, but again, this is not yet a recommended treatment. The main species to look out for are Lactobacillus (L) rhamnosus. L. acidophilus and L. casei. Also, Bifidobacterium (B) lactis and Saccharomyces (S) boulardii. In order for these probiotics to be effective, a dose of 10 billion (10^10) cfu (bacteria) is needed. If the product does not state the dosage, it is likely that it doesn't contain enough bacteria to have any significant effect. Furthermore, a dose way over 10 billion is not beneficial and may cause adverse health effects such as abdominal pain. A study done in The Netherlands compiled a list of recommended probiotics from various manufacturers for the treatment of diarrhoea whilst taking antibiotics. This study was not done in the UK so not all of these probiotics may be available here but it is worth seeing. See this list here. Note that a three-star rating is the best, but a one-star rating is still worth recommendation.

To conclude, we know that microbiomes are extremely important for our health, so look after yours as much as you can.

Want to know what to eat for a healthy gut? Follow this link - https://bbc.in/31Rhfx1

[1] https://physoc.onlinelibrary.wiley.com/doi/10.1113/jphysiol.2004.063388

[2] https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/assessment-of-psychotropiclike-properties-of-a-probiotic-formulation-lactobacillus-helveticus-r0052-and-bifidobacterium-longum-r0175-in-rats-and-human-subjects/2BD9977C6DB7EA40FC9FFA1933C024EA

[3] https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-020-02654-5

[4] https://ieeexplore.ieee.org/document/8110878

[5] https://academic.oup.com/glycob/article/25/4/368/1988548

[6] https://www.researchgate.net/publication/233880834_Transcriptome_analysis_reveals_upregulation_of_bitter_taste_receptors_in_severe_asthmatics

[7] Efficacy of Lactobacillus Administration in School-Age Children with Asthma: A Randomized, Placebo-Controlled Trial - PubMed (nih.gov)

[8] https://www.nejm.org/doi/full/10.1056/NEJMoa1910437?query=featured_home[/et_pb_text][/et_pb_column][/et_pb_row][/et_pb_section]

by GAtherton

Herd immunity to COVID-19 - is it achievable?

What is herd immunity?

Herd immunity to a transmissible infectious agent is achieved when enough people in a population become immune to infection (either naturally or through vaccination) that transmission rates decline. Not every person in the population has to be immune for this to happen, but when the risk of those that aren’t immune coming into contact with someone transmitting the infection become so low that the disease is not able to spread/maintain transmission rate, then we have reached herd immunity.

Each infection differs in contagiousness and so has a different percentage of the population that needs to be immune to achieve herd immunity.

What about COVID-19?

Scientists estimated near the start of the outbreak in 2020 that 60-70% of the population might need to be immune to get herd immunity. However, it is becoming increasingly clear that this pandemic is not behaving as simply as it first seemed. Transmission rates remain high even though up to 95% of the UK population are thought to carry antibodies to COVID-19 and should be at least partially immune.

Why isn’t it happening?

• The vaccine doesn’t completely stop transmission

There are a number of reasons why herd immunity against COVID-19 is appearing to be an elusive target. Firstly, it is important to make clear that whilst the vaccine does reduce the risk of becoming seriously ill from the virus, it only partially blocks transmission. A new study suggests that a person who is fully vaccinated with the Pfizer vaccine and becomes infected with the delta variant is 65% less likely to pass it on compared to an infected non-vaccinated person, and a fully vaccinated person with the AstraZeneca vaccine is 36% less likely to pass it on. These are overall very positive results, especially because the delta variant of COVID-19 is more contagious than the alpha variant against which the vaccine was designed, yet they show that transmission can still occur even from a fully vaccinated person. Most people in the UK owe their immunity to one of the vaccines mentioned in the research article, so herd immunity will be difficult to achieve because our current vaccines don’t guarantee that spreading will be stopped even amongst vaccinated people.

Interestingly, according to the study mentioned above, after about 3 months from the 2^nd vaccine, the transmission doesn’t seem to be stopped at all and if you are infected you become just as likely to pass it on as someone who isn’t vaccinated. Still, if you are vaccinated you are much less likely to catch it and become ill so some benefits remain, and of course, there is a booster vaccine program after 6 months from the 2^nd vaccine which are intended to restore the block to transmission.

Read the full study here - https://bit.ly/3Be5FIu

• Variants

One of the main things stopping the eradication of COVID-19 are new viral variants. A new variant such as delta is capable of causing new waves of infection, especially when vaccine rollout is not yet complete. These new variants may be more transmissible and can be slightly more vaccine-resistant. Therefore, it is key for the majority of the population to become immune before these new variants have time to adapt and emerge.

• Vaccine rollout

Vaccine rollout has not been even among age groups nor between countries. At time of writing in the UK (October 2021), about 79% of people over 12 are double vaccinated. However, vaccinations for 12–15-year-olds didn’t start until September 2021 and those under 12 are not yet being offered a vaccine. This means that whilst the older, more vulnerable people have been vaccinated for some time, the virus has now begun spreading among unvaccinated children (who could then pass it on to their older relatives/people they are in close contact with). In other words, the virus still has a large unprotected population group to infect who have low immunity and so it can continue to spread. Not only this, but although the UK is ahead in terms of vaccine rollout, other countries are not so immune and international travel will continue to be a route by which COVID-19 and its variants are able to spread worldwide.

Vaccine hesitancy has been another big issue in preventing herd immunity. The more people that don’t get vaccinated, the less likely it is that herd immunity will be achieved as it relies on the majority of the population being immune.

• Social behaviour

In the UK, most restrictions are now lifted and mask-wearing and social distancing are no longer legal requirements. Inevitably, people mixing means the virus is now able to spread more easily amongst those that aren’t yet immune and that otherwise wouldn’t have come into contact had restrictions still been in place. In an ideal world, restrictions would remain until herd immunity is achieved, however, this seems unrealistic.

So what does this mean for the future?

Eradication of COVID-19 through herd immunity is not as close as we’d once hoped; it seems we must adapt to a new normal and accept that this virus may be with us for some time as immunity naturally waxes and wanes - much like it does to the common cold and flu. That being said, the success of the vaccination program in the UK would suggest that the worst of the pandemic in terms of severe illness and death is mostly behind us (the prospect of newer, more deadly variants optimistically put aside for now) and as immunity continues to increase with booster vaccines and further natural exposure to COVID-19 infection, it will no longer be such a deadly virus.
Some scientists predict that COVID-19 may become something like the flu with seasonal peaks causing low numbers of hospitalisations and death. Perhaps 'herd immunity' will become an annual cycle of vulnerability to infection (though not necessarily vulnerability to severe symptoms), with natural immunity backed up by annual booster vaccines.

by GAtherton