The importance of microbiomes

December 16, 2021
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