How your brain listens to your Microbes: the gut-brain axis

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60 second summary

  • Communication between out gut microbes and brain is via the brain gut axis
  • Microbes can send messages to our brain via many pathways such as: hormones, immunity signalling molecules and their own metabolites
  • A barrier of cells separating the microorganisms from the bloodstream means that signals are conveyed indirectly

What is the brain gut axis?

One of the most important communication pathways in the body is through the gut brain axis. It is a complex network allowing transport of chemical messages between out brain and digestive tract, mediated through 2 main routes : the autonomic system and circumventricular organs.[1]

Autonomic nervous system (AN)- division of the nervous system controlling non voluntary functions essential for your survival such as heart rate and digestion- functions you don’t have to consciously think about.

Think “autonomous”/ “autonomy” all relating to the prefix auto- which means by itself. The AN is regulated by itself!

Circumventricular organs[2]– structures in the brain with highly permeable vessels called capillaries. These provides an alternative route for hormones to move from neural tissues into the bloodstream.

(This is in contrast to most of the other capillaries in the brain which are hardly accessible to other molecules due to a border of cells called the blood brain barrier.[3])

What does communication via the autonomic system look like?

The main structure responsible for control of the autonomic nervous system in terms of gut-brain communication is the vagus nerve. This nerve is able to detect molecules released by microbes in the gut and transfer them to the central nervous system.

Central nervous system- brain and spinal cord

Appropriate responses from the vagal nerve are crucial in communication. Certain diseases such as Irritable bowel syndrome have shown to have decreased vagal tone.

Vagal tone- the continuous baseline impulses the nerve exerts. [4]

How do microbes communicate with us?

  • The vagus nerve
  • Through hormonal pathways eg HPA axis

HPA axis- also known as the hypothalamic pituitary adrenal axis, it is a set of hormone secreting glands: the hypothalamus, pituitary gland and adrenal gland[5]

  • Immune system via signaling molecules called cytokines
  • And its own metabolites such as short chain fatty acids

Short chain fatty acid- fatty acids with less that 6 carbon atoms produced when gut bacteria ferment fiber in your large intestine. [6]

Are our microbes directly in touch with the vagus nerve?

No, fibers relaying information from the gut to the brain are not found in the lumen of the gut, in other words its inside, which is where the gut bacteria reside. The bacterial layer is separated from the vagus nerve by a single layer of lining cells which are covered in mucus. Molecules releases by microbes are therefore relayed indirectly. Amongst the single layer of cells lining the gut 1% of these are enteroendocrine cells which can detect signals from microbes and then interact with the vagus nerve affecting food intake and gut contractions.

Enteroendocrine cell:

Entero- related to the enteric nervous system. Overall there are 3 types of nervous systems  central nervous system (brain and spinal cord); peripheral nervous system ( rest of nerves) and enteric nervous system (unique to the gut)[7]

-Endocrine= means releasing hormones

The science– enteroendocrine cells can interact with aspects of the vagus nerve by releasing serotonin. The nerve has receptors for serotonin on its surface. Communication can be mediated through other hormones too such as CCK


[1] PMC. (2018). The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808284/ [Accessed 20 Jul. 2019].

[2] Wikipedia. (n.d.). Circumventricular organs. [online] Available at: https://en.wikipedia.org/wiki/Circumventricular_organs [Accessed 20 Jul. 2019].

[3] Wikipedia. (n.d.). Blood brain barrier. [online] Available at: https://en.wikipedia.org/wiki/Blood–brain_barrier [Accessed 20 Jul. 2019].

[4] Wikipedia. (n.d.). Vagal tone. [online] Available at: https://en.wikipedia.org/wiki/Vagal_tone [Accessed 20 Jul. 2019].

[5] 2 minute neuroscience: the HPA axis. (2019). Youtube: Neuroscientifically challenged.

[6] Healthline. (2016). How Short-Chain Fatty Acids Affect Health and Weight. Available at: https://www.healthline.com/nutrition/short-chain-fatty-acids-101#section1 [Accessed 20 Jul. 2019].

[7] Wikipedia. (n.d.). Enteroendocrine cell. [online] Available at: https://en.wikipedia.org/wiki/Enteroendocrine_cell [Accessed 20 Jul. 2019].

The gut- brain axis on weight loss: could removal of the vagus nerve solve the obesity epidemic?

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What is the vagus nerve?

Out of all 12 nerves which arise from the brain, the longest is the 10th also known as the vagus nerve. It is the most complex nerve of the body’s autonomic nervous system, which is the system controlling non voluntary functions such as heart rate and digestion. These are actions you do not have to consciously think about and are a gift from evolution.

In the early days, as soon as single cells started to develop into multicellular organisms having an autonomic system became crucial in order to control various organs in the body simultaneously.[1] In essence, backstage, your body is constantly multitasking in a heroic effort to maintain internal balance.

What is the function of the vagus nerve?

The vagus nerve is partially responsible for the control of the heart, lungs and the digestive tract. It is the main transporter of information from the gut to the central nervous system, also known as the gut-brain axis: from the gut the nerve projects to the brain, specifically the caudal brainstem.

Caudal brainstem- from latin cauda meaning tail, the brainstem is a structure which connects your brain to your spinal cord, the structure running down your back and neck[2].

The vagus nerve and tackling obesity

In terms of controlling food intake, vagal afferents transmit satiety signals from your gut to the brain. Removal of thia nerve is currently being researched as a less invasive alternative weight loss procedure to gastric bypass surgery. [3]

Afferent nerves-carry impulses from organs towards the central nervous system

Efferent nerves- carry impulses from the central nervous system to organs

Gastric bypass surgery- a surgical procedure where staples are used to create a pouch at the top of the stomach. The plumbing of your digestive tract is changed by connecting the small pouch to the small intestine meaning less food is required to achieve satiety.[4]

During this surgery parts of the vagus nerve, such as the ventral and dorsal aspect, are removed whilst other parts remain (such as gastroduodenal branch). Therefore innervation to certain parts of the GI tract such as the pancreas are still provided.

Why is partial/ full removal of the vagus nerve associated with weight loss?

Studies have shown that when the vagus nerve is removed ghrelin levels decrease because of the loss of connection of the autonomic nervous system to ghrelin cells in the stomach.

Ghrelin- the hunger hormone stimulating an increase in appetite and food intake.

Therefore the intensity of messages from the stomach to the brain conveying information about hunger is decreased.

How can gastric bypass surgery and vagus nerve removal have beneficial effects on balancing out glucose levels?

After parts of the vagus nerve being removed in gastric bypass surgery, the secretion of hormones PYY and GLP1 is increased because of dumping of nutrients. This means fast movement of food down the digestive tract decreasing time for the absorption of nutrients. Both hormones affect blood glucose levels.

PYY- Peptide YY is an anorexigenic hormone, meaning it suppresses appetite

GLP1- glucagon like peptide 1 is a hormone promoting insulin secretion so encouraging the uptake and storage of glucose by muscle and liver cells.[5]

All in all the vagus nerve is a key structure in communication between the gut and brain and future studies should be conducted into how altering its anatomy can help sufferers of metabolic diseases.


[1] Science Direct. (2012). Chapter 141 – Evolution of the Cardiovascular Autonomic Nervous System in Vertebrates. [online] Available at: https://www.sciencedirect.com/science/article/pii/B9780123865250001414 [Accessed 19 Jul. 2019].

[2] KidsHealth. (2019). Your Brain & Nervous System. [online] Available at: https://kidshealth.org/en/kids/brain.html [Accessed 19 Jul. 2019].

[3] Wikipedia. (n.d.). The vagus nerve. [online] Available at: https://en.wikipedia.org/wiki/Vagus_nerve [Accessed 19 Jul. 2019].

[4] NHS. (2017). Weight loss surgery. [online] Available at: https://www.nhs.uk/conditions/weight-loss-surgery/types/ [Accessed 19 Jul. 2019].

[5] PMC. (2009). The vagus nerve, food intake and obesity. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597723/ [Accessed 19 Jul. 2019].

Can a vaccination with microbes cure depression?

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60 second summary

  • Inflammation is present in all mental health conditions
  • Increased cases of inflammation are thought to be because of decreased exposure of our immune system to microbes ~ the hygiene hypothesis
  • Mycobacterium vaccae is known to regulated metabolism of molecules associated with mood so could be administered as a therapeutic drug for mood related disorders

In an arduous search for the root cause of a group of common conditions scientists look at the diseases’ common denominators, so symptoms, genes or even lifestyle choices that all individuals share. In terms of mental health disorders inflammation has unveiled itself as a trait shared by all- from obsessive cumpulsive disorder to depression.[1]

Inflammation- process by which the body’s white blood cells and substances they produce protect us from infection with foreign organisms, such as bacteria and viruses.[2]

Over the past few years there has been increased interest in vaccinating individuals with depression which affects approximately 300 million people worldwide[3]. It has been clear to many scientists now that the body and the mind can be tightly linked in dangerous feedback loops.

How could such a vaccination be possible?

Research has found a causal link between depression and increased levels of pro-inflammatory cytokines and tight association between inflammation and mental health issues- simply put:

Inflammation causes mental health issues, and mental health issues themselves provoke inflammation.

 Cytokine- derived from the Greek words “cyto”- cell and “kinos” – movement, these molecules are crucial in immune signaling and activating responses to inflammation and infections[4].

The importance of developing treatments for depression are more important than every before- from 2005-2015 cases of depression increased by nearly a 20%.[5]

Why has depression and inflammation been on the rise?

One of the main suggestions is the “old friends hypothesis” which explains that in our hygiene obsessed world today we have significantly decreased exposure to mud, dirt and large varieties of microbes. Studies in mice which have born without any exposure to bacteria have been shown to have poorly developed lymphoid systems and are susceptible to inflammatory disorders.

Lymphoid system-network of structures in body important in the removal of toxins and waste

 For our immune system to respond adequately to threats it must be educated when we are young , such as by exposure to dirt. Studies have even confirmed that children raised in farms or those with pets are less likely to develop allergies and asthma.

The science- If you allow your body to be exposed to certain pathogens your body’s adaptive immune system reacts and expands its regulatory T cell (Treg) population which are important in supressing other immune cells . For instance B. Fragilis, found in stool and a normal part of the gut microbiome releases a chain of sugars polysaccharide that directly increases Tregs and so restrains activity of immune response inducing cells such as Th17..[6]

M vaccae and the gut

In the 1970’s a research team were trying to figure out why vaccinations for leprosy were more effective in certain area more than others. What they found was that there areas were more abundant in a microbe called Myobacterium vaccae, which naturally originates in soil and was shown to boost the effectiveness of the vaccine. Furthermore in another trial,  when administered to cancer patients alongside chemotherapy, these individuals experienced a significant increase in quality of life, despite not living ay longer than the controls just on chemo.

How does M vaccae work?

The science- In mice experiments M vaccae has been shown to increase serotonin metabolism which is a neurotransmitter in the brain associated with mood regulation. This suggests that ingesting the microbe upregulates serotogenic neurons that modulate stress behaviours.

Despite not being part of today’s normal human microbiome, introduction of this microbe into the body may have significant beneficial effects in terms of immunity and inflammation. It is likely that M vaccae was a resident of the gut microbiome of our ancestors due to their exposure to dirty mud and water. Therefore long term exposure of this microbe is suggested to trigger responses in our adaptive immune system and develop a tolerance to responses in stressful situations. [7]

Overall this research is of great importance and has huge future potential in terms of prevention and treatment of psychiatric disorders.


[1] https://www.vice.com/en_us/article/j5wzn7/the-vaccine-that-could-prevent-stress-anxiety-and-depression?utm_campaign=sharebutton

[2] h WebMd. (n.d.). What Is Inflammation?. [online] Available at: https://www.webmd.com/arthritis/about-inflammation#1 [Accessed 18 Jul. 2019].

[3] Psychology Today. (2017). Depression Is Not a Choice. [online] Available at: https://www.psychologytoday.com/us/blog/teen-angst/201704/depression-is-not-choice [Accessed 18 Jul. 2019].

[4] News Medical. (n.d.). What are Cytokines?. [online] Available at: https://www.news-medical.net/health/What-are-Cytokines.aspx [Accessed 18 Jul. 2019].

[5] The Guardian. (2018). What is depression and why is it rising?. [online] Available at: https://www.theguardian.com/news/2018/jun/04/what-is-depression-and-why-is-it-rising [Accessed 18 Jul. 2019].

[6] Can we vaccinate against depression?. (2012). [ebook] Available at:

Click to access Raison-can-we-vaccinate-against-depression.pdf

[Accessed 18 Jul. 2019].

[7] Ingestion of Mycobacterium vaccae decreases anxiety related behaviour and improves learning in mice. (2013). [ebook] Available at:

Click to access Ingestion-of-Mycobacterium-vaccae-decreases-anxiety-related-behavior-and-improves-learning-in-mice.pdf

[Accessed 18 Jul. 2019]. e(Ii(t)

The epithelial barrier: The single cell thick boundary between you and your microbes

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60 second summary

  • Our gut microbes reside inside the opening of our intestines and a top layer of mucus
  • They are separated from our gut cells by a protective bottom layer of mucus
  • Immune cells can travel through the layers sampling for disease causing bacteria

A healthy gut is abundant in microbes called probiotics.

Probiotics- live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host[1]

These are divided into 3 distinct categories: Bacteroidetes, Firmicutes and Proteobacteria which reside in the opening of your gut called the intestinal lumen and its top layer of mucus. Your gut has a sophisticated structure in which it divides the bacteria from your own cells, whilst still allowing the movement of immune molecules for defense.

What are the layers in the gut?

The top layer is the lumen which comes in direct contact with the food you eat[2].

Next, there is a double layer of mucus. The top layer, in contact with the lumen, is the habitat of many of your microbes: it is spacious with the ability to expand fourfold in volume.[3]

The lower layer of mucus acts as a filter preventing bacteria from entering.

Blow this is the single cell barrier of your own cells called the epithelium.

The science: Overall, there are 4 types of epithelial cells:

1. Enterocytes- which absorb molecules from the intestinal lumen

2. Paneth cells- important in defense by releasing anti-microbial peptides when encountering pathogens[4]

3. Goblet cells- secrete mucus

4. Entero-endocrine cells- produce hormones such as insulin.

The bottom layer of the gut lining is called the lamina propria which is where most of the immunity related cells reside.

The science– one important immunity related cell in the lamina propria is the dendritic cell. The function of these is to take samples from the mucus. If a harmful microbe is encountered the dendritic cell migrates to lymph nodes, sites densely populated with disease fighting T cells, where it activates an immune response.

How is our gut important in immunity?

The epithelial cells lining the gut form the largest interface between our external and internal environment. [5] Our gut microbes are responsible for maintaining this barrier’s integrity by communicating with our immune system.

The science: main mechanisms by which the barrier’s integrity Is modulated are:

1.Increasing activity of immune cells such as macrophages which locate and ‘eat’ foreign cells[6]

2. Secretion of antibodies which neutralize pathogens

3.Secretion of mucus- a sufficient quantity of mucus prevents harmful bacteria from getting in contact with our own cells

4.Competition with pathogenic bacteria for resources such as nutrients and space

Overall our immune system is tightly linked to our microbes and adequate communication between the two is essential in maintaining homeostasis, in other words balance.


[1] Springer Link. (2018). Probiotics and the Gut Immune System: Indirect Regulation. Available at: https://link.springer.com/article/10.1007%2Fs12602-017-9322-6 [Accessed 17 Jul. 2019].

[2] Wikipedia. (n.d.). Lumen (anatomy). [online] Available at: https://en.wikipedia.org/wiki/Lumen_(anatomy) [Accessed 17 Jul. 2019].

[3] PMC. (2013). Role of mucus layers in gut infection and inflammation. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716454/ [Accessed 17 Jul. 2019].

[4] Wikipedia. (n.d.). Paneth cell. [online] Available at: https://en.wikipedia.org/wiki/Paneth_cell [Accessed 17 Jul. 2019].

[5] Mucosal Immunology. (2015). 4th ed. Academic Press, p.16.

[6] Study.com. (n.d.). Macrophages: Definition, Function & Types. Available at: https://study.com/academy/lesson/macrophages-definition-function-types.html [Accessed 17 Jul. 2019].

Looking for a drug tailored to your DNA? Think precision medicine

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60 second summary

  • The microbiome is sequenced by looking for variations in the same gene of different bacterial cells
  • Every disease has a different effect on the bacterial population inside the body
  • By screening and sequencing microbial communities diseases may be treated earlier and more thoroughly with personalised treatment

Are the treatments for diseases we use today really that effective?

Many of the conditions we suffer from in this are what we call multifactorial. This means that they are caused by a variety of contributing factors such as diet, genetics, exposure to pollution etc. In their best efforts, scientists try to manufacture a drug that will suit everybody- by which what is meant is the majority.

Every single person’s body’s reactions are unpredictable and it is difficult to tell who will be most touched by side effects. Therefore recently precision medicine is recently greatly increasing in popularity and demand- the ability to personalize a drug for your disease based on your lifestyle and your DNA brings with it a bounteous amount of opportunities.

Why should microbes be used in precision medicine?

The microbiome is one of the main areas focused on it personalized medicine research. This is because of its profound effects on brisk, short term changes in our health such as the common cold as well as chronic and serious conditions like diabetes and cardiovascular disease. Furthermore, as a result of the rapid advancements of technology, sequencing of a complete bacterial genome can be performed for under one hundred dollars on a lab bench. [1]

How to sequence a microbiome?

Distinguishing the quantity and species of microbes involves taking samples and looking for variations in DNA sequences called genes. Each microbe has a specific sequence so the more types of arrangment you find, the greater the diversity.

The science: Arguably, the most popular method to distinguish the presence of different microbes in an individual is via the 16S rRNA method. 16S rRNA is a gene coding for a molecule used in the production of a ribosomal subunit which is a structure used to form proteins in the body.[2]

How do scientists decide which gene/genes to sequence? There are hundreds!

The 16S rRNA gene used is highly conserved in bacteria meaning that it has been essentially unchanged throughout evolution- it is present in every single bacterium;[3] however it contains regions which are variable and unique to each species of microbe which allow each strain to be differentiated through sequencing.

To what extent do microbial communities vary in different diseases?

The importance of precision medicine in terms of the microbiome is that each disease differs in the way it alters the microbiome, and these differences can even be seen in divergent forms of the same condition. One example of this is Inflammatory Bowel disease (IBD) which affects over 300,000 adults in the UK[4]. It is characterized by abdominal pain diarrhea and cramps[5] which can be divided further with each subdivision presenting its own microbial differences.

The science: IBD divides into: Ulcerative colitis, intermediated colitis and Crohn’s disease

Each of these conditions can be split even further for instance Crohn’s disease into: Ileal Crohn’s disease and Colonic Crohn’s disease.Even at this detailed level of diagnosis population of microbes can be contrasting such as the former having significantly increased bacteria E. Coli compared to the latter.

Importance in sequencing one’s microbiome in terms of disease treatmant

Overlooking a persons microbial ecosystem can also be detrimental because bacteria can alter the efficacy of drugs. For example Paracetamol competes with chemicals produced by microbes and so its degradation in the body is hastened and less of its is available to be absorbed and used- this process differs from person to person which is why developing a safe threshold for medicine doses is hard.

The science: Bacteria in the large intestine produce a metabolite called p-cresol which is a product of fermentation[6]. It competes with Paracetamol in a reaction called )-sulfonation.

O sulfonation- formation of a covalent bond between an oxygen in a substrate and sulfo group.[7]

 This means that only some of the drug can actually be absorbed and used- the rest is broken down and excreted from the body by a process called glucorodination.

Concluding thoughts

Overall, sequencing a persons microbiome has huge future implications in preventative medicine and disease treatment and thorough scientific research is currently being conducted to unmask our gut bacteria’s potential.


[1] PMC. (2018). Microbiome at the Frontier of Personalized Medicine. [online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730337/ [Accessed 16 Jul. 2019].

[2] PMC. (2018). The Human Microbiome and Understanding the 16S rRNA Gene in Translational Nursing Science. [online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535273/ [Accessed 16 Jul. 2019].

[3] Medicine net. (2018). Medical Definition of Evolutionarily conserved gene. Available at: https://www.medicinenet.com/script/main/art.asp?articlekey=3344 [Accessed 16 Jul. 2019].

[4] Crohn’s & Colitis UK. (n.d.). About Inflammatory Bowel Disease. [online] Available at: https://www.crohnsandcolitis.org.uk/about-inflammatory-bowel-diseasehttps://www.crohnsandcolitis.org.uk/about-inflammatory-bowel-disease [Accessed 16 Jul. 2019].

[5] Wikipedia. (n.d.). Inflamatory Bowel Disease. [online] Available at: https://en.wikipedia.org/wiki/Inflammatory_bowel_disease [Accessed 16 Jul. 2019].

[6] Wikipedia. (n.d.). P-Cresol. [online] Available at: https://en.wikipedia.org/wiki/P-Cresol [Accessed 16 Jul. 2019].

[7] Royal Society of Chemistry. (n.d.). O-sulfonation. Available at: https://www.rsc.org/publishing/journals/prospect/ontology.asp?id=MOP:0003559&MSID=c1ob06415k [Accessed 16 Jul. 2019].

Stamina, endurance and the DNA-level modifying effects of Veillonella bacteria

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60 second summary

  • Scientists investigated the abundance of Veillonella bacteria in high performance athletes
  • Veillonella abundance was significantly increased post exercise
  • This bacterium plays a key role in breaking down lactate which is the causative factor in muscle cramps
  • The products of lactate breakdown by this bacterium may increase maximal oxygen consumption during exercise.

An introduction to Veillonella

Veillonalla is a genus of bacteria commonly be found in the intestines and mouth of mammals. It is most commonly known for its ability to breakdown the molecule lactate.

Genus-  a type of ranking in biological classification[1]

What is lactate?

Lactate is a by product of respiration, the release of energy, without oxygen.

In order for energy to be supplied to our muscles for exercise, glucose must be broken down via a pathway called glycolysis. The quantity of energy released is dependent on whether oxygen is present. If it is present up to 38 molecules of ATP may be produced where ATP is the currency of energy in cells and in termed aerobic respiration. During long or intense bursts of exercise our body’s oxygen consumption does not meet the heightened demand so nerobic respiration, the release of energy without oxygen, occurs. This pathway leads to the formation of lactate which  is what causes muscle cramps.

Veillonella bacteria increased in athlete gut microbiomes

In a study on marathon runners and Olympic trail rowers researchers found a significant increase in the genus Veillonella post exercise. Furthermore, changes at the genetic level were seen too- every single gene in the methylmalonyl-CoA pathway, which breaks down lactate, was more abundant.

Effects of lactate breakdown.

The scientists then investigated the specific effect of Veillonella compared to another strain of bacteria which does not break down lactate (Lactibacillus bulgarsis) . The experiment involved injecting mice with either one of bacteria and then testing their treadmill performance;

Results?

The Veillonella group performed significantly better.

How can a microbe alter your fitness?

As mentioned above, Veillonella breakdown lactate via the methylmalonyl CoA pathway. This Lactate is broken down into acetate and propionate.

Methylmalonyl- Co-A pathway=

3 Lactate → acetate + 2 propionate + CO 2+ H 2O[4]

These 2 products are a class of molecules called short chain fatty acids (SCFA’s) which are absorbed into the bloodstream rectum ( lower digestive tract) and drain directly into the vena cava via the pelvic plexus.[2]

Vena cava- large vein which returns blood to the heart

pelvic plexus- a bundle of nerves in the pelvic area

In terms of exercise the SCFA propionate has shown to increase resting energy expenditure as well as maximum oxygen consumption- the latter being crucial in prolonging the body’s ability to utilize oxygen during exercise. These effects of propionate were confirmed as when the scientists administered a group of mice with this molecule compared to salt solution

~their treadmill performance increased accordingly. [3]

Implications

This suggests one day scientists might be able to create an exercise probiotic- a fermented drink or food with the potential to enhance one’s aerobic capacity important for people with activity heavy lives such as soldiers. [5]


[1] Wikipedia. (n.d.). Genus. [online] Available at: https://simple.wikipedia.org/wiki/Genus [Accessed 14 Jul. 2019].

[2] Springer Link. (2016). Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. [online] Available at: https://link.springer.com/article/10.1007/s00535-016-1242-9 [Accessed 14 Jul. 2019].

[3] Research Gate. (2019). Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism. Available at: https://www.researchgate.net/publication/333985452_Meta-omics_analysis_of_elite_athletes_identifies_a_performance-enhancing_microbe_that_functions_via_lactate_metabolism [Accessed 14 Jul. 2019].

[4] Wikipedia. (n.d.). Veillonella. [online] Available at: https://en.wikipedia.org/wiki/Veillonella [Accessed 14 Jul. 2019].

[5] Live science. (2019). Athlete’s gut bacteria boost performance. Available at: https://www.livescience.com/65780-athletes-gut-bacteria-boost-performance.html [Accessed 14 Jul. 2019].

Stool transplants- a new dawn for obesity treatment?

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60 second summary

  • Stool transplants are also known as fecal microbial transplants (FMT’s)
  • They involve the transfer of stool from a healthy individual to the intestines of an ill person
  • Microbes present in the stool colonise the ill persons gut and have the potential to restore balance
  • Studies in mice have shown FMT’s can reverse obesity

Treating obesity with a stool transplant

The past few centuries have seen a rapid incline in metabolic disorders, amongst others- type 2 diabetes, hypercholesterolemia (high cholesterol) and heart disease. It is recently emerging that aside from genetic, lifestyle and environmental factors, the microbes residing in the gut play a large role in the regulation of these maladies.

Studies in mice have shown that there is more to altering a person’s microbial make-up than just by diet which only accounts for 57% of variation- other lifestyle alterations such as feeding patterns and sleep cycles also play a large role.

Main modifications

Modification of a persons microbiome can be achieved through 3 main interventions-

  1. Taking prebiotics such as dietary fiber
  2. Taking probiotics- so beneficial bacteria
  3.  Fecal transplant

Fecal microbiota transplant- transfer of stool from a donor to the  intestines of a recipient to restore bacterial balance. [1]

Fecal transplant intervention

This procedure has been used since the 4th century in the treatment of Clostridium difficile (diarrhea)  where in the Chinese Dong-jin dynasty administration of a stool suspension by mouth to patients with diarrhea yielded positive results.[2] Fecal transplantation is an alternative to antibiotic treatment with some studies showing a 91% primary cure rate. The procedure involves the transplant liquid being administrated into your large intestine through the anus.

Endoscope- a long thin flexible tube used inserted into the body

Fecal transplants and obesity

One area of recent interest has been the treatment of obese individuals with faecal transplants from their lean counterparts. So far, studies have suggested that microbes in the obese, thought to be of the phylum Firmicutes, are more effective at extracting energy from foods. Associations have been made between the increase of Firmicutes bacteria and decreased Bacteroidetes with increasing body mass index. (BMI)[3]

BMI- measure that uses your height and weight to work out if your weight is healthy.[4]

Experiments have found correlations between an increase in Bacteroides and weight loss[5] therefore it seems viable to suggest that altering one’s microbiome through a fecal transplant could potentially have therapeutic and potentially curative effects.

How would a fecal transplant cure obesity?

The first question to answer is what is the cause of obesity? Despite this having a variety of plausible answers one of the most plausible is insulin resistance.

Insulin resistance- when your body doesn’t respond properly to the hormone insulin which is important in removing glucose from your bloodstream into storage.

People suffering with obesity hare said to have low insulin sensitivity which means larger doses of insulin are required to lower blood glucose than in a healthy individual. In studies obesity and insulin resistance in rats has been reversed with fecal microbial transplants.

The scientific mechanisms for this dramatic change is still in question, but 1 thing is known for sure- Microbes play a large role in metabolism of glucose and fat, and this is through a protein found in the liver and intestines called the Farnesoid X receptor (FRX). This receptor works by binding to hormone regulating parts of DNA in a cell’s nucleus affecting gene expression… and it is the microbiome which activates FRX by metabolizing of primary bile acids  to secondary bile acids.[6]

All in all much more research into fecal microbial transplants must be undertaken to satisfy safety and ethical demands of the public but it is a promising technique with life changing potential.


[1] NHS Foundation Trust. (n.d.). Faecal microbiota (stool) transplantation (FMT). [online] Available at:

Click to access fmt.pdf

[Accessed 15 Jul. 2019].

[2] Research Gate. (2012). Should We Standardize the 1,700-Year-Old Fecal Microbiota Transplantation?. [online] Available at: https://www.researchgate.net/publication/233537625_Should_We_Standardize_the_1700-Year-Old_Fecal_Microbiota_Transplantation [Accessed 15 Jul. 2019].

[3] PMC. (2017). Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. [online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440985/ [Accessed 15 Jul. 2019].

[4] NHS. (2016). What is the body mass index (BMI)?. Available at: https://www.nhs.uk/common-health-questions/lifestyle/what-is-the-body-mass-index-bmi/ [Accessed 15 Jul. 2019].

[5] Research gate. (2007). Microbial Ecology: Human gut microbes associated with obesity. Available at: https://www.researchgate.net/publication/6617713_Microbial_Ecology_Human_gut_microbes_associated_with_obesity?enrichId=rgreq-12bd6ba98811af7d0172fb9c544799a1-XXX&enrichSource=Y292ZXJQYWdlOzY2MTc3MTM7QVM6MTYzMzU3Njc2MDIzODA5QDE0MTU5NTg5MTM1ODc%3D&el=1_x_2&_esc=publicationCoverPdf [Accessed 15 Jul. 2019].

[6] Wikipedia. (n.d.). Farnesoid X receptor. [online] Available at: https://en.wikipedia.org/wiki/Farnesoid_X_receptor [Accessed 15 Jul. 2019].

Molecular Mimicry- How your gut bacteria trick your immune system!

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60 second summary

  • Some bacteria have proteins on their surface which mimic those on our own cells
  • They play a crucial role in preventing gut related inflammatory diseases.

The gut and immunity

It has been known for a while that the gut plays a large role in protection against disease: About 80% of the immune system resides inside the gut[1] alongside your microbial community, which also play a protective role by several mechanisms such as  regulation of T cells.[2]

T cells- cells playing a vital role in defense against pathogens .

T cells can distinguish between disease causing cells and safe cells via antigens.

Antigens-molecules found on cells providing information about whether or not the cell is dangerous or infected- in short deciding its fate- should it stay alive?

Recent evidence has shown that some bacteria serve a protective function through mimicking our own antigens.

IGRP206–214   is an antigen found in mice found on cells in the pancreas called islets of Langerhans cells. These cells play a large role in the control of blood sugar levels and development of diseases such as diabetes. One of the functions of this IGPR antigen is to encourage the activity of a subset of immune cells called CD8+ T cells.

CD8+ T cells- (also known as cytotoxic lymphocytes) kill infected cells by mechanisms such as release of toxic granules called perforins into the cell leading to its death.[3]

One of the functions of CD8+T cell is to suppress disease by targeting the destruction of cells presenting the foreign antigens rather than the pancreas’ beta cells.

A type of antigen on the microbial strain Bacteroides called Bacteroides Integrase has been shown to mimic the IGPR protein.  [4]

Quick introduction to Bacteroides

Bacteroides are a species generally beneficial as long as they’re residing inside the gut. However when they esacpe can cause bacteremia which is the presence of bacteria in the bloodstream which is dangerous. Generally these microbes play important roles ,such as in terms of digestion, by fermenting carbohydrates so that can be used as host energy souce. Germ free animals need 30% more calories to maintain body mass than normal mice.

Function of bacterial integrase

The integrase protein found on Bacteroides therefore is able to mimic the IGRP antigen and induce the T cells to kill infected cells rather that the body’s own insulin producing cells which is one of the causes of diabetes.

Another effect of the Bacteroides integrase in mimicking the IGPR antigen is reduction of colitis.

Colitis- inflammation of inner lining of colon. [7]

The mechanism behind this is as follows: Like IGPR, Bacteroides integrase recruits CD8+ cells. This reduces colitis because the stimulated CD8+ cells target inflammation inducing cells called dendritic cells .

Dendritic cells- antigen presenting cells which can lead to the stimulation of an immune response.

One way in which these cells cause inflammation is by over production of TNF alpha which is a molecule also associated with premature cell death. [5]

Overall this contributes to maintenance of a normal immune system.


[1] Institute of health sciences. (n.d.). Probiotics help as 80% of Immune System in your GI Tract. [online] Available at:

Probiotics help as 80% of Immune System in your GI Tract
[Accessed 13 Jul. 2019].

[2] BMJ journals. (2018). Imitation is the best form of… treating IBD?. Available at: https://gut.bmj.com/content/67/2/389 [Accessed 13 Jul. 2019].

[3] British society of Immunology. (n.d.). CD8+ T Cells. Available at: https://www.immunology.org/public-information/bitesized-immunology/células/cd8-t-cells [Accessed 13 Jul. 2019].

[4] MassiveSci. (n.d.). How gut bacteria manipulates your immune system – by mimicking it. Available at: https://massivesci.com/articles/gut-bacteria-immune-system-protein-language/ [Accessed 13 Jul. 2019]./

[5] Wikipedia. (2019). Tumour necrosis factor. [online] Available at: https://en.wikipedia.org/wiki/Tumor_necrosis_factor_alpha [Accessed 13 Jul. 2019].

[6]Research gate. (2017). A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress Colitis. [online] Available at: https://www.researchgate.net/publication/320513212_A_Gut_Microbial_Mimic_that_Hijacks_Diabetogenic_Autoreactivity_to_Suppress_Colitis [Accessed 13 Jul. 2019].

[7] MedicineNet. (n.d.). Colitis. [online] Available at: https://www.medicinenet.com/colitis/article.htm [Accessed 13 Jul. 2019].