The bacteria in your gut affect blood insulin levels and may influence your chances of developing type 2 diabetes

Developing type 2 diabetes is for a large part influenced by your diet but also genes. However, a recent study has now shown that your gut microorganisms might also play an important role in the risk of developing type 2 diabetes (T2D). The article published in Nature Genetics entitled “Causal relationships among the gut microbiome, short-chain fatty acids (SCFA’s) and metabolic diseases”, claims evidence that bacterial metabolites such as SCFA’s are able to influence insulin levels and increase the risk of getting T2D.

Various studies have suggested that increased SCFA production benefits the host by exerting anti-obesity and antidiabetic effects, however, results of different studies are not always in agreement. Moreover, there is also evidence that increased production of SCFAs in the gut might be related to obesity, due to energy accumulation. Resolving these conflicting findings requires a detailed understanding of the causal relationships between the gut-microbiome and host energy metabolism, and the present study contributes to this.

The authors analyzed data from a large population study based in Groningen (The Netherlands), comprising 952 individuals with known genetic data, as well as information on parameters associated with metabolic traits such as BMI and insulin sensitivity. In addition, data were acquired for the type and the function of the bacteria which were present in the gut of the study participants. Combining this data, the authors tried to answer the question of whether changes in microbiome features causally affect metabolic traits or vice versa?

A technique called Mendelian randomization (MR) which is increasingly accepted to establish cause-effect relationships in the onset of diseases was applied. The primary outcome of the analysis was that host genes influence the production of the SCFA butyrate in the gut, which is associated with improved insulin response in the blood after an oral glucose tolerance test. In addition, abnormalities in the production or absorption of propionate, another SCFA, were causally related to an increased risk of T2D.

So far available data suggest that overweight humans or those with type 2 diabetes may have different microorganisms in their gut compared to healthy people. These microorganisms which are commonly found in healthy people are absent from the T2D patients. Whether the differences in the microbiota between healthy and T2D patients are an effect of the disease development or account for causality is challenging to be answered. With the data from the present study, authors are able to go one step further and demonstrate potential routes by which microorganisms are able to regulate our metabolic status underlying their importance for our wellbeing.

Collectively the present article suggests that production of bacterial SCFA’s play a pivotal role in the regulation of metabolic traits such as blood insulin levels and are associated with the onset of T2D.

Since the study was observational and did not include any T2D patients, confirmation of the results is essential. Follow up studies including T2D patients would be highly informative. With the rising prevalence of obesity in adults, which is reaching epidemic levels, the prevalence of T2D will also continue to rise. In the past years, scientists have mainly focused on the role of human gene data, but this has not led to major breakthroughs. Perhaps knowledge of the microbiome will elucidate molecular mechanisms which can be translated to novel effective treatments for metabolic disorders such as T2D.

REFERENCES
Sanna, S., van Zuydam, N. R., Mahajan, A., Kurilshikov, A., Vila, A. V., Võsa, U., . . . Oosting, M. (2019). Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nature genetics, 1.

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MoBa is short for The Norwegian Mother and Child Cohort Study which is a large pregnancy observational study. During the years 1999-2008 pregnant women in Norway were recruited to the study. The study is conducted by the Norwegian Institute of Public Health. Questionnaires regarding health, diet and environment were sent out to the women during and after pregnancy. Women are sent regular follow-up questionnaires. As the child grows up, the child also completes questionnaires. In addition, the fathers were invited to participate with a questionnaire when their partner was pregnant. Biological samples were also collected from the mother, father and child. Today there are 114 500 children, 95 000 mothers and 75 000 fathers participating in the study.

https://www.fhi.no/en/studies/moba/

The study was set up to gain knowledge about the causes behind serious disease. The study is unique because it gathers information from fetal (in vitro) life and follows the offspring into adulthood. In this manner it is possible to look at early influences and later disease. The study is prospective, which means that information about mothers, fathers and their offspring is registered before a disease has manifested itself. With this design, women are asked questions several times during her pregnancy and do not have to try to remember what she did when looking back at her pregnancy.

MoBa is population-based and became nationwide with 50 participating hospitals in Norway. For more information on the many publications based on MoBa data, visit this link:

https://www.fhi.no/en/studies/moba/for-forskere-artikler/publications/

The participating women in MoBa also filled in a questionnaire about eating habits before and during pregnancy.

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Why do some people have a higher craving for carbohydrate-rich and junk-food than others? Why are weight-loss programs more effective in some individuals than others? And why are some people more physically active?

The dopamine system in the brain plays an important role in regulating how much you eat and whether or not you gain weight. When this system does not function optimally, people have a higher craving for junk-food, lower physical activity, and unsuccessful body weight control.

There are two mechanisms that determine food-related behaviour.

The more direct, homeostatic, mechanism constantly surveys the body’s energetic needs and holds them actively in balance. That is homeo-stasis.

The second non-homeostatic mechanism determines the way humans, and other animals, react to food: how willingly and often they will consume it again, and whether they feel anticipation or craving for it.

These behaviours are both largely regulated by the neurotransmitter dopamine, a chemical that conveys information in the brain. Once released by one nerve cell it binds to a receptor, a large molecule on the surface of the adjacent nerve cell, thus changing its functioning. A major component in eating-related behaviour is the dopaminergic D2 receptor (DRD2) that is most abundantly localized in striatum, a brain region activated by food anticipation and consumption1.

The function of the dopaminergic system affects eating and weight-related problems in four ways.

First, in some people, the dopamine system reacts more vigorously in response to food.

Second, this response leads to increased eating and possibly obesity.

Third, overeating and obesity lead to less efficient dopaminergic signaling.

Fourth, this lower dopaminergic signal needs to be compensated by more intense behaviour e.g., more eating2.

For example, in people with lower levels of dopamine D2 receptor, cravings for carbohydrate-rich food and junk-food are more prevalent3,4.

Besides eating-related behaviour, dopamine also affects health/obesity via voluntary physical activity, creating a vicious circle: obesity leads to weaker dopaminergic signal, especially lower levels of DRD2 receptor, and this, in turn, leads to decreased exercise and motivation for physical activity5–7.

Furthermore, individuals with lower levels of DRD2 receptors may benefit less from long-term weight loss programs and are less effective in weight maintenance8,9. Thus, dopamine affects body weight via choice of foods, physical activity, and body weight reduction efficacy. Despite the reasons for food-cravings, part of the solution is acknowledging and managing these impulses. Conscious action towards weight-reduction will lead to less pronounced food-cravings, which in turn leads to favourable solution of weight related problems10.

REFERENCES
1. Wise, R.A. Philos Trans R Soc Lond B Biol Sci 361, 1149–1158 (2006).
2. Alonso-Alonso, M. et al. Nutrition reviews 73, 296–307 (2015).
3. Lek, F.-Y., Ong, H.-H. & Say, Y.-H. Asia Pac J Clin Nutr 27, 707–717 (2018).
4. Yeh, J. et al. Asia Pac J Clin Nutr 25, 424–429 (2016).
5. Kravitz, A.V., O’Neal, T.J. & Friend, D.M. Front Hum Neurosci 10, 514–514 (2016).
6. Matikainen-Ankney, B.A. & Kravitz, A.V. Ann N Y Acad Sci 1428, 221–239 (2018).
7. Ruegsegger, G.N. & Booth, F.W. Front Endocrinol 8, 109–109 (2017).
8. Roth, C.L., Hinney, A., Schur, E.A., Elfers, C.T. & Reinehr, T. BMC Pediatr 13, 197–197 (2013).
9. Winkler, J.K. et al. Nutrition 28, 996–1001 (2012).
10. Smithson, E.F. & Hill, A.J. Eur J Clin Nutr 71, 625 (2016).

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Have you ever heard of the Okinawa Islands, located between Japan and Taiwan, which host one of the longest living people in the world? Even compared with the rest of Japan, to which the islands belong, people grow older on Okinawa.

On average, women become 86 years, men 78 years (1). And more than that, people there maintain a good health up until a very high age. So, what exactly is it that the Okinawans do differently? And what can we change in our lives to get the same positive effects for our health?

Research has extracted many factors that might contribute to this striking longevity, such as a constant moderate physical activity, lack of time pressure and the importance of a solid family structure (see also my blog on effective lifestyle changes here: https://newbrainnutrition.com/four-easy-rules-for-healthy-eating-and-lifestyle/).

What might be easier to change in our everyday lives, however, is the composition of the food we eat.

Let’s investigate what makes the Okinawan diet so healthy (2):

Their diet is rich in root vegetables, especially the very healthy sweet potato. (Who would have guessed that a vegetable carrying the term “sweet” could be more beneficial for your health than its common counterpart?). Sweet potatoes have a high content of dietary fibers, anti-oxidant vitamins A, C and E and anti-inflammatory properties.

They eat many legumes, such as soybeans.

An abundance of mostly green and yellow vegetables is eaten regularly.

Okinawans don’t abstain from meat, alcohol or tea. They consume it in moderation, choosing lean meat and products from the sea.

It seems that no food should be strictly avoided, but that it’s more like the phrase: “Eat everything in moderation and not in abundance.”

Different fruit and medicinal plants (like curcumin or bitter melon) further contribute to a healthy and diverse cuisine.

Altogether, their food is high in unrefined carbohydrates (refined carbohydrates occur e.g. in sweets or white bread, unrefined carbohydrates occur e.g. in brown rice or wholemeal bread) and they consume protein in moderate amounts and mostly plant-based (from legumes, vegetables, but also occasionally from fish or meat).

The Okinawan diet is characterized by a healthy fat profile: rich in omega-3 fatty acids (which occur in fatty fish like salmon, but also in seeds, like flaxseeds, and nuts), high in other polyunsaturated and monounsaturated fatty acids (occurring e.g. in olive oil or avocado, and low in saturated fats (e.g. occuring in butter).

Hence, its composition resembles that of the Mediterranean Diet, which also is associated with a lower risk of cardiovascular disease and other age- and lifestyle-related diseases (Download your free report on the current state of research on the Mediterranean diet here: https://newbrainnutrition.com/the-mediterranean-diet-and-depression-free-report-download/).

By changing our diet and adapting it to the Okinawan (or Mediterranean) diet, you could contribute to a long and healthy life.

Now you might ask how this relates to “new brain nutrition”? Well, a healthy diet affects our gut, which is linked closer to our brain than we originally have assumed (learn more here: https://newbrainnutrition.com/the-gut-brain-axis-an-important-key-to-your-health/​).

Hence, diet should have an impact on our brain health just as on our general health. Substances from fermented soy beans (so-called ​natto), for example, are said to have the potential to prevent the formation of plaque in the brain, which is related to Alzheimer’s disease.

Also, anti-inflammatory effects of a high polyunsaturated fatty acid consumption might have an effect on the production of neurotransmitters (essential for the transfer of information between nerve cells), which largely takes place in the gut.

Interestingly, due to a more western-style cuisine, the younger Okinawans are starting to face the same diseases such as diabetes, high blood pressure, etc, just as people from the rest of the world.

Diet matters. So: What changes in your diet do ​you​ want to start with?

Take the first step and try a typical Okinawa dish: Goya Champuru

1 Goya cucumber (may also be frozen)

1 block tofu, dried and as firm as possible approx. 80-100g

Shabu-Shabu meat (thinly sliced pork); cut meat into bite-sized pieces

1-2 tablespoons soy sauce

1-2 tablespoons rice wine (sake)

1/2 teaspoon salt

2 tablespoons neutral oil (must be suitable for frying!)

2 eggs

For vegetarians: Follow the same recipe, but replace Shabu-Shabu with chopped vegetables like carrots, onions, cabbage and bean sprouts or pumpkin.

Wash the Goya cucumber, cut it in half and remove the seeds with a spoon. Slice thinly, salt it, let it rest for a few minutes. Wash again, press firmly to remove as much water as possible.

Stir-fry the Shabu-Shabu in a tablespoon of oil, salt it afterward.

Add tofu and stir-fry it until it turns slightly dark. Put tofu and Shabu-Shabu aside.

In the same pan, heat another tablespoon of oil and stir-fry the Goya cucumber in high temperature.

Add the meat and tofu, then soy sauce and sake, stir.

Scramble two eggs and add them.

Stir and don’t let the food turn too dry.

Serve the Champuru with rice.

REFERENCES
(1) https://de.wikipedia.org/wiki/Präfektur_Okinawa

(2) Willcox DC; Scapagnini G; Willcox BJ. Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet.Mech Ageing Dev. 2014; 136-137:148-62 (ISSN: 1872-6216); found here: https://www.sciencedirect.com/science/article/pii/S0047637414000037

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Recently, I participated in the Radboud Talks 2019, a scientific pitch competition, where I was lucky to be one of the eight finalists.

Why Radboud Talks? It is a perfect opportunity to share my work/ideas with the world and to gain more experience regarding presentation skills. They organized two workshops beforehand, where I had the opportunity to learn presentation techniques from professionals (actors and science communication advisors). We also received a lot of feedback, so I really learned a lot about how to present my scientific work to a general audience.

Below you can find the video from the preliminaries based on which I was chosen as a finalist. There you can hear about my research project which is about gut bacteria and their potential role in ADHD (Attention Deficit Hyperactivity Disorder). ADHD is a common worldwide neurodevelopmental disorder. Every person with ADHD has a unique combination of symptoms and challenges. Importantly, it has a significant social impact on patients’ lives, causing disruption at school, work and relationships. Despite its societal importance, progress in understanding disease biology has been slow.

 

The study of the human microbiome has become a very popular topic, because of their revealed importance in human physiology and health maintenance. Numerous studies have reported that gut bacteria may have an effect on our mental health. Some studies showed a potential role of gut bacteria in a psychiatric disorder like depression, autism or Parkinson (1). Above all, diet showed to have a profound effect of ADHD symptoms. This was earlier described in this blog: https://newbrainnutrition.com/investigating-the-effects-of-a-dietary-intervention-in-adhd-on-the-brain/ and we know that diet is one of the main factors influencing gut bacteria. Taking all together, I am curious (and investigating) if gut bacteria play a role in ADHD and if yes what kind of effect do they have on ADHD symptoms.

REFERENCES:
Bastiaanssen, T., Cowan, C., Claesson, M. J., Dinan, T. G., & Cryan, J. F. (2018). Making Sense of … the Microbiome in Psychiatry. The international journal of neuropsychopharmacology22(1), 37–52. doi:10.1093/ijnp/pyy067

 

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We have discussed the association between ADHD and obesity in our first blog (https://newbrainnutrition.com/adhd-and-obesity-does-one-cause-the-other/), briefly summarized, evidence from various study designs suggested that shared etiological factors might contribute to the above association. Recently, a large genome-wide association study (GWAS) on risk genes for ADHD reported a significant genetic correlation between ADHD and a higher risk of overweight and obesity, increased BMI, and higher waist-to-hip ratio, which further supported that there could be genetic overlap between obesity and ADHD (1).

Considering the previously described occurrence of unhealthy dietary intake in children and adolescents with ADHD in our second blog (https://newbrainnutrition.com/unhealthy-diets-and-food-addictions-in-adhd/), along with the fact that bad eating behaviours are crucial factors for the development of obesity, We can speculate that the shared genetic effects between ADHD and unhealthy dietary intake may also explain the potential bidirectional diet-ADHD associations. Is there any available evidence to support the above hypothesis?

To date, dopaminergic dysfunctions underpinning reward deficiency processing (or neural reward anticipation), was reported as a potential shared biological mechanism, through which the genetic variants could increase both the risk for ADHD and unhealthy dietary intake or obesity. Via the Gut-Brain axis, a two-way and high-speed connection, the gut can talk to the brain directly. According to the study (2), a higher proportion of bacteria that produce a substance that can be converted into dopamine was found in the intestines of people with ADHD than those without ADHD. Using functional magnetic resonance imaging (fMRI), they further found that the participants with more of these bacteria in their intestines displayed less activity in the reward sections of the brain, which constitutes one of the hallmarks of ADHD. We are therefore proposing the idea that there could be a biological pathway- ‘dietary habits-gut (microorganism)-reward system (dopamine)-ADHD’, through which the shared genetic effects between ADHD and unhealthy dietary intake may play a role.

In order to determine whether the genetic overlap between ADHD and dietary habits actually exists, we will in our next Eat2beNice project use twin methodology and unique data from the Swedish Twin Register. We will keep you updated!

This was co-authored by Henrik Larsson, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.

Authors:
Lin Li, MSc, PhD student in the School of Medical Science, Örebro University, Sweden.

Henrik Larsson, PhD, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.

REFERENCES:
1. Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature genetics. 2019;51(1):63.

2. Aarts E, Ederveen TH, Naaijen J, Zwiers MP, Boekhorst J, Timmerman HM, et al. Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS One. 2017;12(9):e0183509.

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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with an estimated prevalence rate of 5.3% among children and of about 2.5% among adults. It is characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity, being associated with significant impairment of social, academic, and occupational functioning across the lifespan.

However, despite many efforts, the exact etiology of ADHD still remains unknown and data about modificable risk and protective factors are largely lacking. Recent evidence has suggested an association between inflammation, immunological disturbances and ADHD. Supporting this idea, an increased incidence of immune-mediated disorders (e.g. asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, psoriasis, thyrotoxicosis or type 1 diabetes) accompanied by elevated serum/plasma and cerebrospinal levels of inflammatory markers (especially interleukin (IL)-6) or auto-antibody levels (e.g. antibasal ganglia antibodies, antibodies against the dopamine transporter) have been found in these patients.

Importantly, recent studies have shown the gut flora as an important immunoregulator (1-3) and it is hypothesized that an imbalance in the gut microbiota (dysbiosis) may have a negative effect on cerebral development and behavior (4). About 95% of all circulating serotonin, dopamine or noradrenaline precursors are produced by our gut microbiota, being this ‘enteric nervous system’ bidirectional connected to the central nervous system through hormonal or immune/inflammatory pathways.

In line with this, recent findings suggest that some aliments as probiotics can not only revert dysbiosis, but also modulate brain neurodevelopment, activity and improve cognition, mood and behavior due to their immunoregulatory and anti-inflammatory properties (5-7).

Therefore, understanding the microbiota and how the gut connects to the brain would be important both for the better comprehension of the biological bases that underlie some psychiatric disorders such as ADHD, as for the future development of new evidenced-based drugs for these conditions.

This was co-authored by Josep Antoni Ramos-Quiroga, MD PhD psychiatrist and Head of Department of Psychiatry at Hospital Universitari Vall d’Hebron in Barcelona, Spain. He is also professor at Universitat Autònoma de Barcelona.

REFERENCES:

1. Felix KM, Tahsin S, Wu HJ. Host-microbiota interplay in mediating immune disorders. Ann N Y Acad Sci. 2018; 1417(1):57-70.

2. Yadav SK, Boppana S, Ito N, Mindur JE, Mathay MT, Patel A, et al. Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood. Proc Natl Acad Sci U S A.2017; 114(44): E9318-27.

3. Mandl T, Marsal J, Olsson P, Ohlsson B, Andreasson K. Severe intestinal dysbiosis is prevalent in primary Sjögren’s syndrome and is associated with systemic disease activity. Arthritis Res Ther.2017;19(1):237.

4. Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016; 21(6):738-48.

5. Slykerman RF, Kang J, Van Zyl N, Barthow C, Wickens K, Stanley T, et al. Effect of early probiotic supplementation on childhood cognition, behavior and mood. A randomized, placebo-controlled trial. Acta Paediatr.2018; 107(12):2172-78.

6. Kane L, Kinzel J. The effects of probiotics on mood and emotion. JAAPA. 2018; 31(5):1-3.

7. Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci.2011;12(8):453-66

 

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Our body is colonized by trillions of microorganisms that are important for vital processes. Gut microbiota are the microorganisms living in the intestinal gut and play an essential role in digestion, vitamin synthesis and metabolism, among others. The mouth and the large intestine contain the vast majority of gut microbiota whether the stomach only contains few thousands of microorganisms, especially due to the acidity of its fluids. Microbiota composition is constantly changing, affecting the well-being and health of the individual.

Each individual has a unique microbiota composition, and it depends on several factors including diet, diseases, medication and also the genetics of the individual (host) (Figure). Some medicines, especially antibiotics, reduce bacterial diversity. Strong and broad spectrum antibiotics can have longer effects on gut microbiota, some of them up to several years. Genetic variation of an individual also affects the microbiota composition, and the abundance of certain microorganisms is partly genetically determined by the host.

The main contributor to gut microbiota diversity is diet, accounting for 57% of variation. Several studies have demonstrated that diet’s composition has a direct impact on gut microbiota. For example, an study performed on mice showed that “Western diet” (high-fat and sugar diet), alters the composition of microbiota in just one day! On the other hand, vegetarian and calorie restricted diet can also have an effect on gut microbiota composition.

Prebiotics and probiotics are diet strategies more used to control and reestablish the gut microbiota and improve the individual’s health. Probiotics are non-pathogenic microorganisms used as food ingredients (e.g. lactobacillus present in yoghurt) and prebiotics are indigestible food material (e.g. fibers in raw garlic, asparagus and onions), which are nutrients to increase the growth of beneficial microorganisms.

In the last years the new term psychobiotics has been introduced to define live bacteria with beneficial effects on mental health. Psychobiotics are of particular interest for improving the symptomatology of psychiatric disorders and recent preclinical trials have show promising results, particularly in stress, anxiety and depression.

Overall, these approaches are appealing because they can be introduced in food and drink and therefore provide a relatively non-invasive method of manipulating the microbiota.

AUTHORS:
Judit Cabana-Domínguez and Noèlia Fernàndez-Castillo

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How do you eat in a healthy fashion?  Anne Siegl, PhD writes that a big part about eating healthy is nutritional diversity.  Not eating the same thing every day, but providing your body with a rich variety of all kinds of foods and nutrients.  Part of our objective is to keep our gut happy, because our gut drives so much of our health.  And we are discovering that the gut is in continual high-speed two-way communication with the brain.  If the bacteria (microbiota) in your gut are happy, you will lead a more healthy physical life, and we are learning, a more healthy mental life as well.  We are one organism, and it’s all connected.  Keep your gut microbiota healthy with a varied diet.

Download this important report today.

 

 

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Scientific Research has now shown there is a direct connection between your Gut and your Brain.  It’s a two-way, high-speed connection, and your Gut and Brain are in constant communication.  Part of what makes up your gut is microbiota, and these tiny organisms perform important tasks in the body, such as digesting and supplying vital nutrients for both body and brain functioning.  We now know that the health of your gut not only determines your physical health, but has a direct effect on your mental health.

Our New Brain Nutrition researchers are conducting new research on these communication mechanisms and the effect on mental health.
Download your copy of The Gut Brain Axis today, and stay up-to-date on all we are learning.

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