The Alzheimer's disease and the bloodstream-brain barrier

When the brain of patients with Alzheimer's disease was analysed, there was an entire list of disease-causing bacteria, viruses and fungi, and while they were not enough to indicate encefalitis or meningitis, the low levels of pathogens will slowly wear down your defences, making your brain to function suboptimally. It was not really like an all-out war, but more like a sabotage. These findings are both surprising and concerning, as previous it was hypothetised that Alzheimer's disease (AD) is not infectious. 

Oral bacteria have been found repeatedly in the brain of people suffering with AD , as some of their excretions (protein based) were found also. The culprits are Porphyromonas gingivalis. Fusobacterium nucleatun and Prevotella intermedia. Herpex simplex virus (HSV) can live for decades in the nerve cells from your face and lips (trigeminal ganglion cells), causing cold sores when you are stressed or sunburned, but they can also migrate through the same nerve into the brain, producing mild, chronic inflammation, associated with AD. 

Syphilis causing bacterium - Treponema pallidum, can live in the body for years, eventually infecting the brain and causing dementia. AD seems to activate a similar pathway, but instead of one single organism causing this, in the case of AD, the mild chronic inflammtion seems to be caused by many different microorganisms associated together. 

Another notable presence, The Lyme disease spirochete - Borrelia burgdorferi, has been found in the brain of AD patients. This one is carried by a deer tick in most of the cases, and you can get it when the tick bite you and inject you with its saliva. Sometimes you will get some additional friends of Borrelia, such as Ehrlichia (infecting white blood cells), Bartonella (infecting blood vessels) or Babesia (relative of malaria parasite, attacking red blood cells). A very dangerous coktail. Want more distressing news? There are also some fungi that can be found in the brain of the AD patients. There is no single organism to cause AD, but the main problem may be the response to so many different infectious agents. 

Normally the brain is well protected by the blood-brain barrier, with few rare cases when this barrier can break down, similar with the leaky gut issue. Sometimes is the nose ( a known problem of cocaine users), sometimes is the gut (via the vagus nerve) and in very rare cases through the eye. All the dementogens will use one of these routes (dementogen - causal factor of dementia, like in cancerigen - cancer). In AD, the abnormalities related to the blood-brain barrier tend to appear very early, and there are substantial claims related to the link between the nasal and sinusal acces to the brain and the AD type 3. 

The test to verify this issue it is called Cyrex Array 20, and the result must be, obviously, negative. 

Next post will be about gluten related sensitivities.

Have a wonderful day!

G. 

Alzheimer's disease and the links to the gut intestinal flora

In the latest years the scientific research community turned towards the gut microbiota endless possibilities to improve our health. We are becoming more aware of this every month passing by (you can find more in-depth information related to the gut intestinal flora in my own book treating this subject). 

So, the leaky gut was just recognized lately as a medical problem, and it is noticed quite often in our patients, contributing to increased inflammation and other various conditions. Just think about this! Many of us will do everything possible to secure our house, to ensure that everything is locked, roof is in perfect condition, windows closed and pipes are well maintained. Yet, we do not take a similar approach to tighten the barriers in our body, starting with crucial systems like our gut. 

All the cells lining our gastrointestinal tract need to maintain tight junctions (this will happen as a protein complex with occludin acts like a sealant between our cells). The cell lining will keep the food inside our gut and only few selected molecules such as aminoacids resulted from proteins breaking down can pass through and reach the bloodstream, being carried everywhere throrough the body. Sometimes this cell junction starts to loosen up, under the influence of soft drinks or alcohol, chemicals from pesticids, sugar, processed foods, gluten sensitivity, preservatives, yeast, inflammation, chronic stress and medication (aspirin and acetaminophen are just two examples of it). As the cell lining is loosening up, bigger molecules trespass (glucose, fructose, vitamins, various bacteria and yeast). All these new molecules are identified by our body as being intruders, triggering inflammation. Even more, because some of our own cells contain or are similar with the new molecules, sometimes an autoimmune condition is triggered, with our own tissue getting collateral damage. You start with persistent low level inflammation and you can go all the way up to dangerous autoimmune diseases like multiple sclerosis, lupus or arhtritis. When we spoke about Alzheimer's disease (AD) types, i mentioned that type 1 has inflammation as a key cause, and clearly having a leaky gut will increase the risks of AD type 1 as one of the most common way to generate a systemic inflammation is a leaky gut. 

There are many ways to test our gut permeability. One test will measure the urine sugar level and check what kind of sugars are present in it, after we ingested different sugars like lactulose and mannitol, the mannitol goes through the gut barrier, while the lactulose shouldn't. If we have manitol in our urine, that is proof that the gut can absorb the necesarry molecules, but if we have lactulose, this will translate in having a leaky gut. Antibodies to the gut barrier protein will also indicate a leaky gut. There is an antibody array called Cyrex Array 2, and the result should be negative. To test for food sensitivities, you can use Cyrex Arrays 3 and 4, or you can eliminate the foods you suspect they are triggering a reaction, and introduce them one by one, to find out when the symptoms reappear. 

In the next post i will write about the bloodstream-brain barrier. 

Have a wonderful day!

The other brain - a new book that i just finished (with special thanks to the lock-down)

And it is done, after almost one year and a half. I try to make it short and not very complicated, and i hope you will enjoy reading it. My book about the gut microbiome, our microbial intestinal flora. At the moment, as i just launched the book, you can have it at a discounted price.
Here is the link for:

Ebook

Paperback

''I will start the first chapter, talking about our microbiome, or in layman terms, our gut intestinal flora, the microbes living inside of us and how they are actively helping us. It is an interesting subject, and the latest researches seem to just start to discover how important our relation with our non-pathogenic bacteria and microbes is. These days we keep hearing different opinions about this elusive thing called microbiome. What is that and how it can help us? You are in the right place to find out about it, in the next chapters of this book.''

What it is about?

Here are the contents of every chapter:
1 Introduction
2 History and discovery
3 The life cycle of the gut microbiota
4 Food for thought
5 Is every gut microbiota unique?
6 Malnutrition and microbiota
7 Prebiotics, probiotics and synbiotics
8 Inflammatory bowel diseases
9 Microbial diversity and their importance
10 Anatomical correlations with the gut microbiota

I really hope that you will find time to read it and learn a bit more about the latest researches related to health, microbiota and longevity.
Have a good day!
G.

Microbiota - medical therapy

There are application in the food industry. Prebiotic fibers and probiotic organisms are added to infant nutrition to modulate microbiota. Lately there is a transition from prebiotic approach to synbiotic approach ( combining prebiotic fibers with specific microorganisms that can be stimulated by those prebiotic fibers). This is a breakthrough and it is already applied to the infant formula. Bifidobacterium and lactic acid bacteria are the ones used at the moment, with other beneficial bacteria researched for future use. There are ideas for the use of synbiotics to tackle allergies or to further support development of an healthy immune system. Many people now are fully aware of the antibiotic side effects on microbiome and they want to know more about how to modulate the microbiome in a positive health direction.

There are also applications in the animal health and food chain. There is a ban on antimicrobial promoters in some countries for a better quality. In hatcheries, for eggs and poultry, when there is no hen touch, faecal transplantation is used (dried poultry poop), just to mention one example. In the future there will be more methods to modulate and manipulate the microbiota.

And talking about faecal transplantation, there are at least 15 stool banks in the world right now, with the Openbiome in U.S.A. being the biggest. The stools can be used in treating Clostridium difficile, assisting in research for IBS and some other diseases. Only 2.5% of the potential donors are suitable after they are tested. In Netherlands for example, the stool bank has only 8 active donors and they treated 70-80 patients until now.

With this little accolade, our journey of knowledge of microbiota is finished at the moment. I hope everyone enjoyed this and you can give me ideas about other major new researches that you want to learn about.

See you soon!
G.

Microbiota - Inflammatory Bowel Diseases (IBD)

IBD is a group of conditions in which the colon and/or the small intestine becomes inflamed. Crohn's disease and ulcerative diseases are the two main types of Inflammatory Bowel Disease. In Crohn's disease both small and large intestine are affected, and in some rare cases even the mouth, oesophagus and the stomach. In ulcerative colitis only the large intestine and the rectum are affected. 

IBD is a chronic disease with two different states, a high active state of the disease called active inflammation and an inactive state called remission. In the active state the inflammation is accompanied by unpaired barrier function, so the defense mechanism is not properly working. 

Are there any ways for our body to keep the intestinal barrier function as good as possible? First, a layer of epithelial cells connected by tight junctions, covered with a mucus layer to protect the mucosal surface from harmful bacteria and molecules. Second, on top of this layer, we got the gut microbiota that is covering the mucus layer with the good, inoffensive microbes. 

IBD is emerging as a worldwide epidemic, especially in the high income countries, making researchers to think that all these diseases are mainly caused by the environment. The lifestyle in developed countries might impair the microbial colonization. There are multiple factors involver: birth at hospital, with or without caesarean delivery, decreased family sizes, decreased contact with soil organisms, increased antibiotic use, body washing with antibacterial soap and shower gel, increased use of processed foods. The gut microbiota plays a big role in priming and regulating the immune system. In IBD the microbiota changes in composition, being an essential factor driving the inflammation. Markers of IBD can be found in the microbiota, such as reduction of microbial diversity and increase in gammaproteobacteria (this group holds many potential pathogens). 

Gammaproteobacteria

Adherent-invasive microbes like E.Coli and Fusiobacterium can be found, combined with a decrease of beneficial ones (Bifidobacterium, Lactobacillus and F. prausnitzii). All these signs can be used to diagnose the disease. These changes can affect the microbiota as a whole, decreasing the short chain fatty acids like Butyrate, increasing the oxidative stress, causing imbalance between reactive oxygen species and antioxidant defences, causing tissue damage.

Attempts to restore microbiota composition using microbiota based therapies showed positive and promising results, causing remission in IBD, but each patient response is different, and faecal microbiota transplant methods are not superior to the current therapies. But microbiota based therapies can be used in the future to treat and diagnose IBD.

Next post will be the last post of the microbiota series, and it iwll be about the medical therapy. 

Microbiota - Next Gen Probiotics

This next generation probiotics can be helpful in new personalised therapies. They are made from microorganisms used to improve health, you can found them in foods and supplements. The ones sold today are mainly lactic acid producing bacteria like bifidobacteria and lactobacillus, isolated from yogurt and milk.

Lactobacillus reuteri

The next generation probiotics can come from the human gut microbiota and they will be used as a medical therapy instead of only improving health. They will be used in conjunction with bacterial cultivation, genome sequencing and tools to modify bacterial genomes. Their range is extended by our ever increasing knowledge of the composition and function of the human gut microbiome. The Next-Gen probiotics are coming from healthy humans. Take Clostridium Difficile infection (CDI) for example, which is prevented by the healthy microbiota acting as a barrier. However, using antibiotics (this being a major risk factor), can be weakened. We can use antibiotic also as an effective treatment for CDI, but because of the consequences mentioned before, relapse occurs on up to 30% of the patients. There were attempts of successfully eliminate CDI via faecal transplantation, and one of the more promising species was identified for future use. It is called Lactobacillus reuteri and it is a bacterium producing an antibacterial compound called reuterin, using glycerol. This bacteria has antibiotic resistance, preventing the recurrence of CDI.

Other promising candidates are Faecalibacterium prausnitii, Eubacterium halii, Bacteroides Fragilis and Akkermansia muciniphila. Take the last one, Akkermansia muciniphila, which is present in low levels in the intestinal tract of the individuals who have Diabetes type 2 or are obese. Tested on mice, reduced the body weight, enhanced glucose tolerance and decreased the presence of endotoxins in blood. The major difference from the actual probiotics is that the new ones will originate from the human microbiota and will be used for personalised therapies (if a patient is lacking certain beneficial microbes, they will be administered). But they are not on the market yet and further research is needed at the moment.

Akkermansia muciniphila

Microbiota - The faecal microbiota transplant

The faecal transplant os a very good tool to prove a causative role of our gut microbiome in curing different diseases. Because of this reason, the interest in faecal microbiota transplant is rising. We mentioned some research done on mice, but this is a well known practice, and we have a Chinese medical manual from the 4th century A.C. describing the procedure done on humans, as a remedy for food poisoning. But how do we do it today? A healthy donor donates a stool sample, which is tested for certain diseases, frozen and given to the patient later by a tube or as capsules, in order to reach the small intestine. Enema can be also used. This is working by restoring a gut microbiome that it is out of balance, bringing equilibrium and leaving hardly any room for pathogens. However, use of antibiotics and some other factors can disrupt the balance, allowing the pathogens like clostridium difficile to cause infections (symptoms are chronic gut inflammation and persistent diarrhoea). Using antibiotics to cure an infection with clostridium difficile is not effective, as the disease is recurring, and the bacteria is becoming resistant to antibiotics, because this clostridium difficile can colonize an altered microbiota composition. By restoring the microbiota composition, 90% of the patients were cured.

In this case, the faecal transplant is more efficient that antibiotics. Because the gut microbiota of a healthy donor is introduced, restoring the balance and breaking the cycle of the disease. When the healthy microbiota colonize the inside, no more room is left for Clostridium Difficile. Small results were also found in patients with diabetes type 2. Many scientists work to replace the fecal transplants with an odourless mix of bacterial strains derived from the human fecal material.

Do not try this at home, does not matter how many Youtube video you see about this.

The following post will be about the next generation probiotics.

See you soon!
G.

Microbiota - personalized nutrition

Everyone knows that we should eat more fibers and less saturated fats, but personalized nutrition is more than that. We are talking about choosing the healthy nutrition that it is different for different people. You need to take in account diseases you had or got, the genetic and physiological differences, character, habits and social environment.

Each of us is different, and our response to diet or even the same dietary component is different. Let's say caffeine for example: one can drink it after dinner and sleep well at night, while another cannot sleep if is drinking coffee after lunch. Your body and behaviour is complex, and it will determine how you respond to a new diet.

One research group from Israel tried to make a prediction based on one's glycemic response ( the glycemic response to food is the effect of that food on the blood glucose levels). They found out that different people react very different towards identical food components. The 800 participants that their blood sugar measured every 5 minutes with a special device, and they also used and app to report what and when they ate, when they sleep and how long and when they exercise. In the end their stool samples were collected and their composition and activity of the gut microbiota was measured. After all the data was collected, they made an algorithm that could successfully predict the blood glucose response for the participants. This was also used to successfully predict the response of 100 new participants, so this algorithm can be used to predict someone response to a dietary component and to advise a personalized diet. The conclusion was that some people respond very different to the same food product, so for these people some diets will not work, or even have the exact opposite effect. For one of the subjects, they got a bigger response eating lean fish that eating ice cream. This can happen because of our genetics, our lifestyle and our microbiota is different. The response to food is due to all these personal settings. The ability of a person to measure blood glucose levels is a key factor in the development of diabetes and obesity. A specific diet for a weight loss usually aim to control glucose levels and yet different people are told to use the same diets.

In the future is possible that the personalized diet will be a common occurrence, helping us to be healthier and live longer.

That's it for today, next post will be about faecal microbiota transplant.

See you soon!
G.

Microbiota - Synbiotics

Synbiotics are a mixture of probiotics and prebiotics that beneficially affect the host. By combining these tow in a food product, this will lead to a better chance of survival and activity of microbes in the gut.

The interaction for two or more things in order to produce a combined effect greater than the sum of their separate effects it is called synergy. Synbiotics are a mixture of probiotics and prebiotics that beneficially affect the host, with a better survival chance of the probiotics during the passage through the large intestine, avoiding to be made inactive by the high acidic environment present in our stomach, to increase the overall gut health. Once in the intestine, they can start fermenting right away, increasing the activity and growth or the microbiota. The prebiotic can also affect the stool consistency and the bowel movement. Probiotic strains of lactobacilli and bifidobacteria are combined with mixtures of fibers (FOS, GOS, inulin) to create a synbiotic. Synbiotics were tested to help different gut diseases like inflammatory bowel , irritable bowel syndrome, cancer, liver diseases and allergies.

My next post will be about personalized nutrition. See  you soon!

G.

Microbiota - Probiotics

Probiotics were originally introduced as the opposite of antibiotics, living microorganisms consumed to restore the microbiota that we lost after antibiotic treatments. A probiotic is a live microorganism which provide a health benefit to the host and promote gut health when administered in adequate amounts. A probiotic can strengthen the immune system, prevent infection with pathogens, compensate an unhealthy change in our microbiota or an infection by shortening the time of recovery for our microbiome, and even provide extra energy via more short chain fatty acids.

They provide hope in treating lactose intolerance, infections and post-antibiotic diarrhea, immunomodulation for allergies and chronic bowel inflammatory diseases. The biggest challenge is to make them to reach intestine alive, surviving the storage and the acidic medium of our stomach, and delivering the desired concentration in the end (which is strain dependent). We are aiming for 10 at the 7th colony forming units pre milliliter of product. Lactobacillus and bifidobacteria are the most used antibiotics.

Tomorrow i will talk a bit about synbiotics. Have a nice day!

G.

Microbiota - Prebiotics

What are the prebiotics, you would ask? They are fibres stimulating the microbial growth in the gut, when eaten, improving the gut health. These fibres can escape digestion in the small intestine, but once they reach the colon , they will be partially or completely fermented by the gut microbiota. The composition and the activity of the gut microbiota changes, because the microbes able to degrade those kind of fibres are favoured in their growth, and this is beneficial for the host (us).

Prebiotics fibres are made of oligosaccharides, chains of sugar molecules. The most known prebiotics are galactooligosaccharide (GOS), made of chains of galactose sugars and fructo-oligosaccharide (FOS) or inulin, made of fructose sugars. FOS and inulin can be found naturally in plants (onion, garlic, wheat, banana, chicory and various cereals). GOS are made by workers in dairy factories, converting lactose using beta-galactosidase enzymes. As they are digested by our microbiota, short chain fatty acids will be produced, and they will be used as an energy source, to reduce pain or influence the metabolism. 

Prebiotics like GOS, FOS and inulin are very good to stimulate the growth of Bifidobacterium and Lactobacillus microbe species/ Both of them are commonly found in breast fed babies, and sometimes are added to the formula and infant milk to mimic the effect of breastmilk and increase Bifidobacterium and Lactobacillus in infant's microbiota. They are also added to breakfast cereals, bars of cereals, cheese and custard. Apart from the microbiota fermentation product altering the host response, prebiotics can stimulate bowel movements and help with constipation, as they increase the stool weight, due to the prebiotic and the water attracted by the prebiotic.

Lactobacillus reuteri

Conclusion: Prebiotics are fibres that arrive in the colon intact. Here they are degraded, leading to the growth stimulation of the beneficial microbes in the gut. The microbial activity combined with the higher water content of the faeces will result in improved gastric health. 

Next post will be about probiotics. 

See you soon,

G.

Microbial therapies and diagnostics

We all should know that regarding us and our microbes, we work together to harvest the maximum of energy from our food and to fight against pathogens. But which is the best way to keep our microbiota healthy? Everybody heard, i hope, about prebiotics and probiotics. But anyway, i will try to explain a bit more. There are some fibers called prebiotics, that are beneficial to our microbiota. Also, there are some live cultures of microbes that can stimulate our gut health, once added to our diet. The composition of our microbiota can provide personal information about you, and can be used to develop personal food strategies. Our microbiota holds information that can help us to diagnose certain diseases too. So, while our microbes can tell about our health, they can be also used to improve our health and cure certain diseases. One example is the use of faecal transplant therapy to treat recurrent Clostridium difficile, with a bigger success rate than antibiotics and a lowest rate of recurrence.

I will do next a more indepth blog post about probiotics and prebiotics. See you soon!
G.

Unintended consequences and longevity theories

Motto: "Until you make the uncoscious conscious, it will direct your fate and you will call it FATE."
Carl Jung

Yes, we are doing some small scale damages to our macro-Universe, as we are destroying our planet and slowly depleting the earthly resources. We are killing ourselves in unnecessary wars, or indirectly by not taking enough care of ourselves. But this cannot even start to compare with the potential damages. We are playing gods with forces and energies we cannot even fathom to understand, do not make me even start to talk about how we try to control them. We are trying to understand, and in our journey, we are using cannons to hit targets as big as a fly. The damages are irreparable, and they tend to be passible to reoccurence. They come back to bite us when we do not even expect. I will not talk about the atomic power and the energies of the atoms right now. This is too easy to understand. Boom, and the human race is no more.

I will try to raise awareness about another hidden danger. The total lack of care of our microbiome (and by this i mean the 1000000000000000 bacteria living in our gut) is coming back with a vengeance. By creating something inocous such as sweeteners, we modified the human microbiota for generations to come. We caused potential diseases such as leaky gut syndrome, auto-immune diseases, inflammatory bowel dsisease, obesity, allergies, cardio-vascular diseases, cancer and maybe some other that we did not realise yet. One of the direct link to all these problems seems to be microbiota dysbiosis (also called dysbacteriosis, is a term for a microbial imbalance or maladaptation on or inside the body, such as an impaired microbiota). More about this, there are bacteria like Bacteroides Fragilis, which can improve neurological symptoms related to the autism spectrum disorder (ASD), and Lactobacillus helveticus, which can greatly improve the behavioural, cognitive and biochemical aberrations caused by chronic restraint stress. In messing up unwillingly with out microbiota, we make it posible for a whole pletora of diseases to appear or increase their occurence. we messed up physically, emotionally and mentally too.

Keep in mind that using a cycle of antibiotics will kill the beneficial microbes also, not only the pathogens, just to give another example. Seems a paradox, but as our knowledge increase, our potential to erase ourselves as a race increases also. We are very efficient in destroying the pathogens, but this can have unexpected consequences. We are forgetting that dirt is good, and that the difficulties will make us more resistant as an organism.

Maybe this is the reason why we did not encounter any aliens yet, as any civilization that advance too quickly will self-destruct at some moment in their evolution.

Think about this.

G.

Microbiota - Undernutrition and weight loss

The term malnutrition refers to deficiencies, excesses or imbalances in a person intake or nutrients and energy and addresses to three groups of conditions:

1. Undernutrition
2. Micronutrient related malnutrition
3. Overweight.

1. Undernutrition - If you don't have enough nutrients, you are malnourished. It is not always the lack of food, but the lack of quality food. Undernutrition means that you have a shortage of calories and most often of essential nutrients (when the access to food is denied). This is a specific type of malnourishment. As a result, you are being underweight, wasted, growth  is stunted, happening usually after a weight loss event such as infectious disease associated with diarrhea. Stunting means that a person has a low height for age, and it is the result of a long term undernutrition during childhood, holding the child back from achieving their physical and intellectual potential. being underweight is a child with a low weight for age, and you can also be stunted or wasted.

There are clear differences in the gut of the undernourished people compared with healthy individuals. Most of the researches on undernutrition are focused on children, because they need fast growth for their optimal development. Undernutrition in children can have long term health implications: reduced growth rate, immune and cognitive development.

In the same time, the gut microbiota of the undernourished children remains immature. But we do not know if this is a cause or a consequence. In a mice study, after transferring the gut microbiota of a malnourished infant donor, the mice will gain less weight than the ones receiving microbiota from a healthy donor. Undernourished infants often miss bacteria from Ruminococcus and Clostridium group. All those bacteria are the ones producing the short chain fatty acid called butyrate (which is an energy source for the host cells). The microbiota can contribute to the caloric value of your food. This is useful especially when food is scarce, and any part is needed as usable energy.

Ruminococcus bacteria

Another type of malnutrition is Anorexia Nervosa (which is characterized by distorted body image, extreme dieting and the anxiety of becoming obese as main underlying factors). All these symptoms will lead to severe weight loss. Even if it seems different that the undernourishment in children, the common element is the nutrient shortage. And similar changes are noticed in the composition of the microbiota. Anorexia patients will have lower amounts of total bacteria and obligate anaerobic bacteria. In addition, they will also have lower amounts of butyrate producing bacteria and higher amounts of mucin degrading bacteria.

The undernutrition is affecting the microbiota and plays a role in the severity of the undernutrition by releasing less energy from food. The manipulation of the gut microbiota could be a helpful solution for undernourished children.

Next post: Microbial therapies and diagnostics

Microbiota and obesity

Our gut bacteria can be partially blamed for being overweight or obese. There is a causal link between the microbiota and obesity, driven in combination with overnutrition and drastic lifestyle changes.

The prevalence of obesity is reported to increase worldwide and it is a major challenge in our modern days. There are various attempts to explain the large increase in obesity, mostly due to the last three decades of research. They include calorie intake, changes in dietary composition, decrease in physical activity and changes in the gut microbiome. Is the gut microbiota contributing to the excessive weight accumulation in our body? A piece of evidence was published in 2005, when scientist found that obese mice microbiota composition is different from the healthy lean ones. An increase of Phylum Firmicutes bacteria was noticed in the obese mices, and their microbial diversity was lower than normal. This made them wonder if is obesity causing the changes in the microbiota or is the gut bacteria causing obesity? They got sample from human twins (one fat, one lean) and give them to germ free mice. The ones with bacteria from the slim ones stayed slim, the others quickly gained weight. So the conclusion was that there is a direct causal link between the gut microbiota and the weight gain. The next trials started with gut microbes from lean humans, given to obese individuals, and they improved their metabolic response and experienced weight loss. The effect lasted for few weeks when the study was done, but we do not know if the effect is sustained. Also, fecal transplant is prone to high risk of infection. We will talk later about this.

The gut microbiota is a major contributor to obesity. Our diet is another one, as the Western style diet is an example , characterized by highly processed and refined foods, rich in proteins and fats. It has a high salt, fat and sugar content, with protein mainly from red meat. This diet is the major contributor to the actual crysis of obesity and to a wide range of obesity related diseases. This type of diet leads to a low presence of bacteroidetes and akkermansia, followed by an increase in the firmicutes and proteobacteria groups. These alterations were associated with obesity and the subsecvent related chronic diseases. The high fat content causes an overload in energy leading to obesity, but the change in microbiota can also cause inflammation, which in turn can lead to many obesity related diseases.

Diet can increase obesity and obesity related diseases directly and indirectly. The evidence supporting the link between obesity and lifestyle changes is very strong. Modulation of the microbiota might help to ameliorate metabolic responses and initial weight loss attempts. Adapting the microbiota might be useful to keep a healthy weight or even to lose weight.

Next post: Undernutrition and weight loss.

See you soon.
G.

Microbiota - Man versus mice

There are clear differences between the genomes and diets of different species. Is there some evolutionary relationship of animal microbiota? There is indeed a definite difference between the genomes and diets of different animal species. Choosing the microbiome of the elephant, panda, python and few others for study, the microbiota of different animals will form clusters based of their evolutionary distance and dietary behaviour. We got herbivores, carnivores and omnivores. If we look for similarities based on the types of microbes and their abundance in the gut, then animals who are evolutionary close are also more alike on the microbiome level. But even for a big group like herbivores, there are clusters, based on whether the animal is a foregut or hindgut fermenter. Let me explain. A foregut fermenter has a fermenting chamber called rumen placed before the stomach. A hindgut fermenter has a fermenting chamber called cecum at the end of small intestine. Because they are different evolved digestive organs, they are selective for different microbes, hence the difference in the microbiota. The microbes are different based on the evolutionary relatedness of the host, but this clear separation dissapear when we consider the microbiota gene content. The gut microbial communities all share genes with similar functions, so even if the microbes are different, the functions executed are similar.

There was an experiment done, where zebra microbiota was transplanted to germ free mices. The microbes had to find a previous balance in their overall structure, adapting to the new host in the same time. The new environment forces the macrobiota to reach a new stable state. The new environmental conditions are determined by host genetics and lead to specific immune system and physiology, but they are also determined by the host dietary habits. There was another experiment where microbes where transferred from mices to germ free mice and from fish to germ free fish. The conclusion was that the host genetics is of major importance for the microbiota development. The mouse itself will adapt to the new microbiome using immune and metabolic adjustments.

So, the microbiome will adapt to its specific environment as the genetic make-up of the host and its dietary habits will determine the environmental conditions. Every animal species carry their own specific microbiota.

Next post : Microbiota and obesity. Now this will be an interesting one!

Microbiota - twins and siblings

Your genetic makeup is an important factor determining what your microbiota looks like. Let's explore the close relationship between diet and genes.

The example used is the one of two twins, whom are genetically identical. However, their microbiome is not identical, due to the different environmental factors that they were exposed. Twin number one doesn't like veggies, and twin number two is vegan. They also have a sister who can eat everything. She is genetically different that the twins, so if we compare the twins with her, their microbiome becomes very similar, but if we compare the sister microbiome with other people outside her family, all three of the siblings share more similarities. The reasons behind this observation lays within their genes and their shared environment. They are born by the same mother and they are often eating same food.

Looking even wider, they share common similarities with the whole human race, compared with the rest of the animals. The genetic background is a very important co-founder for microbiota's composition, influencing the elusive relationship between your own microbes and the diet. The way of how each host microbes evolved in case of humans is clearly distinct from that of other animals. Even the genetic differences between different human beings influences the microbiota composition.

In conclusion, the transmission of our microbiota and the establishment of a stable microbiota depends on environment, genetic information and diet (eating habits).

Next post: Microbiota - about mice and men

Microbiota - Community types

The human gut microbiota is different in all the humans being worldwide, so your microbiota is like your personal fingerprint. However, there are many similarities between different microbiota, and this information can be used by us to develop health biomarkers and to define therapeutic strategies.

The human gut consists in trillions of microbes and the whole ecosystem varies between individuals in diversity, distribution and abundance. In any ecosystem the selective pressures, disturbances and survival conditions are very important in defining the species leading to a distinct community type in that area. There was a study on human microbiome investigating the impact of possible steering factors such as the dietary habits. The observation underlines that certain combination of microbes, distribution and diversity can lead to a distinct community structure. But, even more important, the people can be grouped in 3 main groups, in a similar way to the blood group type. They can have a high number of Bacteroides, Prevotella or Ruminococcus. People eating a diet with less fibre and high in animal fat tend to have the Bacteroides community, people with a diet high in fibre and low in animal fat tend to have Prevotella community type and finally, was shown that every individual will have a gradient from high to low abundances on these three groups of bacteria. You can see that different dietary habits can support different microbes, and changes to diet can shift the percentage of each community type.

There is also the concept of the genes present in the microbial complex, which will define the potential of degrading complex fibres. So now the community type will also include this microbial gene into information. It turned out that some of us have high gene righness and others can have low gene richness. This low and high gene count can be used to separate individuals in a population. If you got inflammatory bowel disorder and obesity, you will usually have low gene richness. You are also more likely to get more weight than someone with high gene richness. All these concepts can be used to predict individual susceptibility to gain weight.

Even if the individual microbiota is different for each person, there are characteristics that are overlaping. Knowing how a community will respond to a diet and other pressures helps to develop health biomarkers and therapies.

Next post will be about twins and siblings microbiota.

Have a nice evening!
G.

Microbiota - dietary habits

As I promised, after i finished the Autism course, i will come back to the microbiota series.

Now, the course is finished, so we will talk today about dietary habits. We all know that our diet determine what our microbiota can feed off. So, knowing this, we can change our microbiota changing our diet.

How can we do that? Easy, but you need to learn about it. You want to lose weight, you will use a calorie deficit diet, and once you reached the desired weight, you stop. This move will have a drastic effect on your microbiota, but as soon as your eating habits are back to normal, your microbiota will regulate too, because it developed a stable state over the years, and that it is not easily disturbed.

I have read about an interesting study, where they switched the diets of a population of African-Americans with that of the rural Africans. The African-Americans were given a high fibre, low fat African style diet. The rural Africans were given high fat, low fibre Western style diet. After a while, the African style diet was shown to support beneficial microbes and improved function, the Western style diet increased the risk of cancer. This research shows how short dietary changes can affect our microbiome and health.

In order to understand the long term effects of dietary habits, the researchers studied a number of individuals from different countries. People from Western world with  a diet of high protein and low fibre content tend to have more Bacteroides bacteria. People from rural Africa tend to have more Prevotella bacteria. With all the advances regarding food, we are losing our ancestral microbiome due to changes in our dietary habits and surrounding environmental factors. This can have a negative effect on health, leading to diabetes development, colon cancer, I.B.D., all of them being more prevalent in the western world.

I hope you enjoyed this new introduction. Next post will be about community types.

See you soon.
G.

Macrobiota - mucus and milk fermentation

The food that you consume is the one feeding your microbiome. Everything that cannot be digested by yourself it is used by your microbiome, which will transform all these indigestible components into energy that it is used by you.

Some beneficial microbes nibble on you eating the mucus produced by your body, as the human body will produce around 10 liters of mucus every day. The mucus is made of a protein backbone with chains of sugar molecules attached to it, known as mucus glycans. Some microbes adapted to eat these glycan structures produced by our body. These microbes are specialized in the consumption of the host-produced glycans, such as in mucus. Another type of glycans produced by the human body are the human milk oligosaccharides. The glycans in mucus and human milk are structurally alike, they are awkward sugars, rarely found in plants. This is why not many microbes can degrade these glycans.

The dietary glycan starch is a sugar chain of only glucose molecules, while primary sugars of mucus and milk glycans are n-acetilglucosamine, fucose, manose and sialic acid. Because these can be used by the microbiota, they are considered pre-biotic substances to nurture specific microorganisms (who serve a beneficial and protective role for the most).

The group of bacteria specialized in the degradation of the human milk oligosaccharides are known as bifidobacteria. In early life , bifidobacteria plays a role in energy harvest for the infant, they also play a crucial role in the immune and metabolic imprinting. Later in life, permanent colonization of the mucosal layer also leads to immune and metabolic regulation contributing to the host health. Because many pathogens use mucus as a signal to attack, the beneficial mucus colonizing microbiota members will protect against such pathogens. The host tolerates microbes in the mucosal layer and even produce extra mucus when sensing their presence. Another reason of existence of awkward sugars is that, if all bacteria will degrade the mucosal layer, this could be problematic.

In conclusion, some microbiota members like eating the glycans from mucus and milk. Early life, they release energy from human milk, later in life they serve as a line of defense against pathogens. They also stimulate a healthy host immune and metabolic response. Our body will nurture specific members of the microbiota by producing special sugars.

Next post will be about long versus short dietary habits.

See you soon!
G.