Microbiome Center periodically sends insights flashes to all associated doctors.
Below you find an overview of all important flashes that have been sent until now.
29: The microbiome-migraine connection
The gut microbiome plays role in migraine
Migraine is a debilitating, highly prevalent condition that affects approximately 15% of the population. It is well-known that many migraineurs experience nausea or vomiting, but other GI complaints occur often too. For example, migraineurs have IBS 2-4 times more often than healthy peers (1,2). This is a strong indication that gut health is linked to migraine.
In recent years, several mechanisms have been identified that can play a role in the microbiome-migraine connection. For example, impaired anatomical barriers such as the gut-blood and blood-brain barrier are observed in migraineurs and can lead to systemic and neuroinflammatory responses (3,4). Insulin signaling is also impaired in migraine patients and it is known that the microbiome can directly modulate this (4,5).
In addition, it is well-known that disturbed serotonin signaling plays an important role in the pathogenesis of migraine (6). Importantly, metabolism of its precursor tryptophan via the serotonin, indole, or kynurenine pathways is influenced by the gut microbiome (7). It is known, for example, that metabolites from the kynurenine pathway affect the NMDA receptor, which plays a role in the cortical spreading depression phase of migraine. Interestingly, various tryptophan metabolites are disturbed in IBS patients too.
Another potential mechanism that has been identified is pathogen overgrowth. For example, Heliobacter pylori infection is associated with migraine (7). Moreover, overgrowth of other pathogenic bacteria and yeasts has been found in migraineurs as well (8). Since many pathogenic bacterial species are known to be able to synthesize histamine, it is interesting that histamine oversensitivity is implicated in migraine too (9).
Together, the identification of these mechanisms suggests that if a migraine patient also has GI complaints, a function-focused fecal analysis can help to identify which pathways may be involved in that individual. Based on this and on other complaints and medical problems, a targeted intervention can be compiled.
28: New ingredient: pasteurized Akkermansia muciniphila
Pasteurized Akkermansia muciniphila, a postbiotic
In approximately one in eight stool analyses Akkermansia muciniphila is extremely depleted (less than 1×105 CFU/g) and in a larger group it is substantially depleted. This is an indication of a disturbed mucus layer, which forms an important part of the gut barrier. A. muciniphila is known to enhance the integrity of the intestinal epithelial cells and the thickness of the mucus layer and participates in the host immune regulation, thereby promoting intestinal health (1). Interestingly, important parts of the beneficial effects of A. muciniphila can be traced back to Amuc_1100, a specific pili-like protein isolated from the outer membrane of A. muciniphila (2). This is why pasteurized A. muciniphila is as effective as live cells, as demonstrated in, amongst others, the one human study to date (3). Because A. muciniphila is pasteurized and thus the active ingredient does not consist of living bacteria, it is called a postbiotic (4).
The aforementioned RCT shows that supplementation with pasteurized A. muciniphilaleads to lowering of insulin resistance as well as weight (and body fat) loss (3). This effect is supported by evidence from numerous animal studies, as shown for example in a systematic review of ten animal studies (5). These and other therapeutic effects (e.g. on colitis or allergies) are linked to its inflammation lowering and gut barrier restoring effects, as shown in both the RCT and many animal studies (3, and e.g. 6, 7). This includes stimulation of mucus production and increased mucus layer thickness (6).
As of February 1st, pasteurized A. muciniphila is available as new building block that you can select as ingredient for MyOwnBlend. More information on this postbiotic and its effects can be found under the (i)-button on our platform.
We organize a webinar to provide further backgrounds on the role of A. muciniphila in health and disease on February 23rd and March 21st from 19:30-21:00h. If you are interested to join, you can reply to this e-mail, including which date you prefer.
27: New strain effective in acne and caries
New strain: Lacticaseibacillus rhamnosus SP1
When we encounter interesting ingredients for microbiome treatments, we try to make these available for you so that the possibilities to treat patients continue to expand. We have now added the strain Lacticaseibacillus rhamnosus SP1 which has been studied, among others, for its effect on acne and on caries. Importantly, many effects are strain-specific and there are many strains of the L. rhamnosus species. It must be noted that not all strains of this species can be expected to have the same effect as this strain named SP1.
A small but well-conducted RCT with L. rhamnosus SP1 shows that it leads to improved or markedly improved acne symptoms compared to placebo (1). In addition, this study showed that the use of L. rhamnosus SP1 induced a clear reduction of expression of insulin-like growth factor 1 (IGF1) in skin samples of the probiotic group compared to placebo, which is evidence for an effect on insulin signaling. Indeed, accumulating evidence shows that disturbed gut microbiota is associated with acne, partly due to its effect on insulin signaling, but clinical trials with probiotic interventions are scarce (2). This in itself makes L. rhamnosus SP1 an interesting addition.
Another study conducted with this strain is a large RCT (and a subgroup analysis thereof) that investigated the effect of this strain on the prevention of caries in preschool children. The results shows that, compared to placebo, L. rhamnosus SP1 effectively prevents caries (3,4). Another RCT on oral health provides evidence for an effect on Candida-associated denture stomatitis (5). This study also provides direct evidence for an inhibiting effect on (oral) candida.
More information on this strain and its effects can be found under the (i)-button on our platform.
26: Correlation between depression and Enterobacter
In the complete client population the prevalence of depressed mood is about 18%. However, in clients who have high levels of potentially pathogenic Enterobacter species in their fecal analysis results, the prevalence of depressed mood is almost twice as high, namely 29%. This suggests that this potential pathogen is associated with depression.
A literature search reveals similar findings, although less explicit, showing that bipolar depression patients have higher levels of Enterobacter spp. compared to healthy controls (1). The same was found in patients with late-life depression (2). The researchers of the first study also describe an association between increased inflammatory activity and Enterobacter spp. overgrowth. Inflammation is known to be linked to depression (3). Together, our findings and the literature suggest that elevated Enterobacter spp. may cause inflammation and consequently lead to depression. That is a useful insight, because specific probiotic strains are known to inhibit potential pathogens such as Enterobacter spp. and lower inflammation, and thus may be useful in clients with depression.
This is just one example of how we generate insights while helping clients. Together, we learn from practice and continuously improve treatments. If you want to know more please let us know, or attend the webinars about data analysis (November 14th, in Dutch) or depression (December 14th, in Dutch). These webinars will be repeated in English early 2023.
25: L. plantarum DR7, arthritis and microbial butyrate
Another strain has been added to the list from which you can select, the L. plantarum DR7. This strain has been isolated from fresh cow’s milk in Malaysia (1). It has anti-inflammatory effects, shown both in preclinical and clinical studies (2-4), and stimulates AMPK activity (5). AMPK (adenosine 5′-monophosphate-activated protein kinase) is a cellular energy sensor and lowered AMPK activity is linked to insulin resistance, amongst others (6). In fact, one of the mechanisms of action of the well-known antidiabetic drug metformin is via activation of AMPK (7). Treatment with metformin has effects on many conditions, including reducing anxiety, which is thought to be linked to its effect on AMPK (8). Interestingly, a high quality RCT shows that this AMPK-stimulating L. plantarum DR7 strain indeed reduces stress and anxiety (4). In addition, this strain can inhibit respiratory pathogens in vitro and has been shown to be efficacious in reducing incidence and severity of upper respiratory tract infections in a RCT (4,9). Additional evidence and information about this strain can be found at the description of this ingredient in our system.
Rheumatoid arthritis linked to low levels of microbial butyrate
A very sophisticated study, published in Science Advances in February this year, has found that intestinal butyrate-metabolizing species play a role in rheumatoid arthritis (10). Here, the term “butyrate-metabolizing” refers to both butyrate production as well as butyrate consumption, and the investigators found that the number of butyrate-consuming species was much higher in treatment-naïve rheumatoid arthritis patients than in healthy controls. In fact, no less than 51 of 55 of the rheumatoid arthritis-associated butyrate metabolizers were butyrate consumers, 46 of which were enriched in rheumatoid arthritis patients. This suggests that in rheumatoid arthritis the level of microbial butyrate available to the host is substantially decreased. Next, the researchers validated the finding of the skewed butyrate producers/consumers ratio in an independent cohort. In this second cohort it was also shown that indeed both fecal and serum levels of butyrate were decreased in rheumatoid arthritis patients compared to healthy controls. Finally, the investigators showed that supplementation of butyrate in an animal model of arthritis led to a substantial lower arthritis incidence (11% vs. 85%) and severity compared to controls. Together, these findings provide strong evidence for a role of butyrate-metabolizing species in rheumatoid arthritis. This suggests that interventions with butyrate-producing species such as Anaerobutyricum soehngenii or Clostridium butyricum, both available via our platform, may be beneficial.
24: Internationalization, summer breeze, fibromyalgia
At the time of its foundation, in 2018, Microbiome Center started its service in The Netherlands. Since then, more and more doctors from other countries found us and wanted to use personalized microbiome treatment in their practice. From 2021 onward we have therefore expanded our service to other European countries. Today, the Microbiome Center service is available for doctors in six countries, including Germany, Switzerland, and Belgium. To serve all these new colleagues in our network, the ‘Kennisflits’ that we periodically send will be written in English from now on and is called ‘Insights flash’.
Summer breeze: do farts have a microbiome?
Summertime allows for some fun and therefore we asked ourselves the question if farts would have a microbiome. There is some seriousness in this question too, because it is known that microbiota transmission occurs between people living close together, yet little is known about the actual routes of transmission (1-3). Given the fact that everyone of us on average passes gas about ten times a day (4), there has been surprisingly little research into the microbial composition of farts. In fact, we could only find a single publication, which can hardly be called a study. An investigator tested whether or not he could culture bacteria from a colleagues’ farts and indeed he could (5). Given the fact that many bacteria are not culturable, it would not be surprising that farts contain many more live microbes and potentially play a role in microbial transmission.
Microbiome and fibromyalgia
Although the number and quality of studies is still relatively low, it is known that the gut microbiome and microbial metabolite profile in fibromyalgia (FM) patients is altered compared to healthy individuals (6,7). A recently published study adds some new insights to this scarcely studied topic. Researchers found alterations in levels of secondary bile acids and the abundance of bacterial species known to metabolize bile acids in FM patients compared to matched healthy controls (8). The secondary bile acid called alpha-muricholic acid was found to be five times less present in FM patients than in healthy controls and a lower level correlated with increased symptom severity of pain, fatigue, unrefreshing sleep and cognitive complaints. This insight may open up new roads to treat FM patients, e.g. using probiotic strains capable of producing alpha-muricholic acid.
22: New strain, new prebiotic
Recently we were able to add a unique strain to the range from which you can choose, the Latilactobacillus sakei probio65. This bacterium has been isolated from kimchi and has excellent gastrointestinal survival (1). Much research has been devoted to the effect of L. sakei probio65 on atopic eczema. This includes in vitro and preclinical studies (see e.g. 1-3), but also two well-conducted RCTs (4,5). The latter show quite strong effects on various aspects of atopic eczema. Furthermore, in vitro research shows a fairly strong inhibitory effect on various pathogens (1). Interestingly, this strain can also inhibit -glucosidase and α-amylase activity (6,7). These are enzymes that break down carbohydrates and inhibition of these enzymes is seen as a way to treat diabetes and is the mechanism of action of the diabetes drug acarbose (6). Indeed, an animal model showed an improvement in blood sugar after administration of L. sakei probio65 (6), indicating that this strain may also be useful in metabolic syndrome and diabetes. Other evidence and information about this building block can be found in the description of this ingredient in our system.
On June 28, we will explain the effects in atopic eczema in more detail in our webinar about allergy.
New prebiotic: PHGG
Many fibers and prebiotics have been studied in fairly high doses. Thirty grams a day is not uncommon. In addition, literature and practice show that the most well-known prebiotics, FOS and GOS, regularly cause unwanted side effects such as bloating or abdominal pain. One of the exceptions to this is partially hydrolyzed guar gum (PHGG). In addition to the usual higher daily doses, PHGG has also been studied in a dose of approximately 5 grams per day. Guar gum is extracted from the guar bean and is inherently extremely viscous, which is why it is partially hydrolyzed enzymatically (8). Particularly in the 1980s and 1990s, a great deal of research has been done into the effect on glucose response and insulin resistance (with different doses), which consistently shows a beneficial effect (see e.g. 9 and 10). This makes PHGG a good choice as an ingredient in patients with metabolic syndrome, (pre)diabetes, or other indications of insulin resistance. In addition, a lot of research has been done that has shown a beneficial effect on abdominal complaints such as diarrhea, constipation, abdominal pain, and IBS (see eg 8,11,12). A well-conducted study also shows a beneficial effect for SIBO (13), which makes PHGG a good addition to SIBO treatment. Other evidence and information about this building block can be found in the description of this ingredient in our system.
21: SIBO - Small Intestinal Bacterial Overgrowth
Patients with SIBO often complain of bloating and abdominal pain, worse after eating. They may also suffer from persistent belching and flatulence, diarrhea or constipation, impaired fat absorption, vitamin deficiencies (including B12), a disturbed intestinal barrier and impaired immune activity (2).
With chronic abdominal complaints, it is often advised to take extra fiber in the form of supplements or fiber-rich food, but this worsens the complaints in SIBO because it enhances bacterial overgrowth. Practical experience shows that many classic probiotic strains often have the opposite effect. From this point of view, SIBO is sometimes treated with antibiotics such as rifaximin (2,3). While this may provide relief, it may also further disrupt the microbiome and lead to C. difficile infection and AB resistance. It is therefore recommended to intervene on the causes: improving motility, lower intake of short carbohydrates and fasting (1,4,5).
In addition, probiotics can also be used, if properly chosen: a meta-analysis of clinical studies shows that certain probiotics can reduce SIBO complaints (6). But not all strains are suitable. Among the ingredients available for MyOwnBlend are several strains for which clinical research is available that show effect in SIBO. This concerns, among others, the Bacillus coagulans Unique IS-2 (7) and the Enterococcus faecium in combination with. Bacillus subtilis (8). The evidence behind the different strains can be found in the description of the ingredients in our system.
In the past six months, various colleagues have often used a combination of specific strains at SIBO and have received many positive reactions. When you indicate in the Advice Help that there are complaints that are consistent with SIBO, these strains will appear in the proposed recipe. Recently, the SIBO approach has been further supported with the option of taking the probiotics semi-fermented. The patient then receives a thermos flask from MiBlend with an adapted instructions for use that improves the effectiveness high in the small intestine. The first user experiences are positive.
20: Probiotics with anxiety and tension
Probiotics with anxiety and tension
We recently added the Lactiplantibacillus plantarum P-8 to our portfolio. A well-conducted RCT shows that this strain is effective against anxiety and tension (1). The same study also found evidence for an effect against stress, albeit slightly less strong (1). That this probiotic has a beneficial effect on anxiety and tension fits with the growing body of research showing that the microbiome plays a role in anxiety, tension, and depression (2) and that probiotics can improve this (3). It is suspected that this effect has to do with, among other things, the influence of the microbiome and probiotics on inflammatory activity (2.4). Anti-inflammatory effects have also been seen in L. plantarum P-8 in studies with the single strain or in combination with other strains (1,5,6). There is also evidence in animal models that this strain has an effect on oxidative stress (7.8), an aspect that is also associated with anxiety, tension and depression (9,10). Finally, it is interesting that research with L. plantarum P-8 shows that this strain can increase secretory IgA (11,12), as it is known that stress can lead to decreased sIgA excretion (13). It can be concluded that the microbiome influences multiple mechanisms involved in anxiety and tension and that probiotics can modulate this.
Further evidence and information about this strain can be found in the description of this ingredient in our system.
19: Nutrition & probiotics, and invitation Long-Covid
Nutrition and/or probiotics: when are they most promising?
We are regularly asked whether adjusting diet and lifestyle is not enough to restore the microbiome. Indeed, it is known that an adjustment of the diet within one or a few days can change the composition of the microbiome, just like exposure to stress (1,2). However, research also shows that the effects vary from person to person. Just as a healthy microbiome is resistant to perturbations, a disturbed microbiome can also be stable and unaffected by interventions (3). This is called stability or resilience (3,4,5). The microbiome forms a complex ecosystem that can be compared to a forest. Rainfall, an insect infestation, or a forest fire influence the composition of the vegetation in a forest, but the ecosystem as such usually recovers after such pertubation. Sometimes the disturbances in an ecosystem are so great that it does not return to a healthy state comparable to the initial situation. The microbiome has then reached a new stable but dysbiotic equilibrium point that is difficult to return to a healthy equilibrium point (3). If diet and lifestyle have insufficient effect, an intervention with personalized probiotics is an approach that can be considered to move from the unhealthy to a healthy equilibrium point (4,6).
PASC (Long-Covid) and the Microbiome: Invitation
In Knowledge Flash #10 we already paid attention to the relationship between Covid-19 and the gut microbiome (7). More research has since been published showing an important role of the microbiome and gut permeability (8). It is itself hypothesized that the microbiome may play a role in fighting viruses such as SARS-CoV-2 (9).
In recent months it has become clear that relatively many Covid patients have long-term, post-infectious complaints. Although the term Lung Covid is often used for this, “post-acute sequelae of COVID-19” (PASC) is a better description (10). Post-infectious symptoms are not unique to Covid-19; in most bacterial and viral infections, chronic complaints develop in a subgroup of infected patients (10). There are a large number of mechanisms suspected of being involved in PASC (Reference 8 provides an excellent overview) and one of these is a disrupted gut microbiome.
We suspect that microbiome intervention may be supportive of the recovery process in certain cases. We are curious about your experiences and would like to learn with you whether and how microbiome therapy contributes to the recovery of PASC.
Do you have PASC patients in your practice who also have microbiome disruption or abdominal complaints? Then we would like to invite you to contact us and share your experiences with us. If you don’t have time to write it down, you can also call. We make an overview of the cases and experiences of you and your colleagues in order to extract new insights from this and share it with all colleagues. In this way, together we can make the cycle of experience-knowledge-application as short as possible. We would also like to hear from you if you have suggestions about how we can tackle this and which parties we can work with. We are very curious if we can get something like this going together.
nationalgeographic.nl/ darmflora-zou-ingezet-kunnen- worden-in-strijd-tegen- virussen
18: New packaging for maintenance prescriptions
We regularly receive questions about the follow-up process after a MyOwnBlend treatment. Our advice until now has been to repeat a previously prescribed prescription and let it be used as needed. However, the expiration date of 3 months made it difficult for patients to use it for a longer period of time. To solve this, we have developed a new form of packaging. This consists of 12 vacuum-sealed pouches (bags) of 100 grams each. The pouches can be frozen for up to 1 year, and removed from the freezer individually as required. In doing so, ask the patient to follow the thawing instructions in the package insert to ensure that the probiotic bacteria in the pouches withstand thawing (i.e. do not become moist from opening too quickly). After opening, a pouch has a shelf life of 2 months. This option is available to you from today. It is only possible to prescribe the pouches after prior treatment. See enclosed package leaflet for further details.
Requests for repeat prescriptions by patients
From our patient service conversations, we have learned that several patients need an easy way to request a repeat prescription from their treating physician. To meet this wish, we have added a button on the home page of patients with which they can place a request for a repeat prescription. It is then up to you, as the attending physician, whether or not to honor this request. If you receive such a request, you will see an orange notification button on your homepage. If you click on this you can accept or reject the request, with which you put your digital signature under the prescription.
We have also made it easier for you to repeat a previously compiled recipe. In the overview of all recipes (accessible via the ‘Prescriptions’ button in the menu on the left) there is a repeat icon behind all eligible recipes. A repeat button is also shown on the detail page of a recipe. If you click on the repeat button, you will be taken to the familiar page for creating a recipe, on which all ingredients are pre-filled. You can opt for all available packaging forms, including the pouches mentioned above. You can also adjust the recipe if desired.
16: Abdominal complaints, healthy aging
Abdominal complaints in chronic conditions
The majority of the Dutch, almost 10 million people, have one or more chronic conditions (1). More than 3.7 million Dutch people with an MDL disorder are known to their GP and the majority (2.5 million) concerns abdominal complaints such as abdominal pain and constipation (2). In many cases, chronic diseases are accompanied by abdominal complaints and this may be an indication that the microbiome plays a role. For example, abdominal complaints such as constipation, reflux, and diarrhea are more common with headache (3), migraine patients relatively often have IBS (4), and about half of all diabetes patients have abdominal complaints (5,6). Many patients are reluctant to talk about stomach complaints or experience things like abdominal pain, diarrhea, or constipation as normal due to years of habituation. It makes sense to ask about abdominal complaints, because this can quickly provide insight into whether the microbiome may play a role and that can give a new perspective to treat long-term complaints. Asking about stomach complaints fits in every consultation hour. Simple tools for this (such as the Bristol stool chart and a list of questions) are available at MC.
Healthy aging with a unique microbiome
A recent publication shows that a more unique microbiome correlates with better health in the elderly (7). Different cohorts were used and these showed that the uniqueness of the microbiome increases with age and that the extent to which this happens is significant. The degree of uniqueness was found to be correlated with certain metabolites that were associated with very advanced age in previous studies. In addition, the degree of uniqueness of the microbiome was directly correlated with several indicators of health in the elderly (drug use, self-perception of health, size of living space, walking speed). Taken together, this research provides fairly strong indications that the microbiome plays a determinant role in healthy aging.
https://doi.org/10.1038/s42255-021-00348-0 (available as a preprint at https://doi.org/10.1101/2020.02.26.966747)
17: New strains, mechanisms
Two new strains in one building block
We recently added a new building block that this time consists of two new strains: an Enterococcus faecium and a Bacillus subtilis strain. These two strains are the active ingredients of a drug that has been marketed and extensively researched in Asia. For example, a meta-analysis of 53 RCTs shows that this combination of strains is effective in ulcerative colitis (1). This meta-analysis also provides direct evidence for an effect on inflammation. RCTs also show evidence for an effect on abdominal pain and IBS (2,3), and small intestinal bacterial overgrowth (SIBO)(4), and a retrospective study provides evidence for an effect in antibiotic-associated diarrhea (5). Other evidence and information about this building block can be found in the description of this ingredient in our system.
Important mechanisms behind chronic diseases
In the previous flash of knowledge, it was discussed that almost 10 million Dutch people have one or more chronic conditions. Two important mechanisms in chronic diseases are insulin resistance and systemic low-grade inflammation. These mechanisms are best known in the metabolic syndrome and type 2 diabetes, but it doesn’t stop there. They play a role in (almost) all chronic conditions. To illustrate, some (perhaps unexpected) examples of this are depression (6-8), rheumatism (9,10), and ME/CFS (11,12). Both insulin resistance and systemic low-grade inflammation are directly related to the microbiome (13-16). It can therefore be concluded that it is useful to take these two important mechanisms and the role of the microbiome into account in the therapeutic regimen in all chronic diseases.
15: New ingredient; psoriasis
At the request of several colleagues, we have added 2′-fucosyllactose (2’FL) to the list of ingredients for you to choose from. 2’FL is a so-called ‘human milk oligosaccharide’ and is naturally present in breast milk. Such breast milk oligosaccharides contribute to the development of the microbiome and the tuning of the immune system. These effects are thought to occur in adults as well, and 2′-fucosyllactose has been found to be safe in adults (1). Interestingly, there is preclinical evidence that Akkermansia muciniphila can grow on 2’FL (2-4), suggesting that 2’FL is one of the few compounds that can stimulate this important bacterial species. Akkermansia muciniphila is a bacterial species that is important for health, which breaks down mucin and thus stimulates a healthy intestinal wall and is often greatly reduced in diseases (5,6). It is perhaps therefore not unexpected that preclinical evidence shows that 2’FL improves intestinal barrier function (7.8). Furthermore, there is some evidence from human studies for an effect on anti-inflammatory (9), allergies (10), and respiratory infections (11). Other evidence and information can be found in the description of this ingredient in our system.
Role of gut microbiome in psoriasis
Although psoriasis is known as a skin disease, there are several indications that the gut microbiome plays a role (12,13). This is probably related to the fact that psoriasis has a compromised immune system and low-grade inflammation (14,15). Many of the comorbidities found in psoriasis (such as type 2 diabetes, non-alcoholic fatty liver, depression, cardiovascular disease, and Crohn’s disease (14,15)) are related to the core factors of the metabolic syndrome: systemic low-grade inflammation and insulin resistance. The latter is also found in psoriasis (16,17). The gut microbiome is known to play an important role in these underlying mechanisms, including through its effect on gut permeability. This fits with the observation that gut barrier function is impaired in psoriasis (18). All of this suggests that microbiome therapy such as probiotics may be of benefit in psoriasis. Indeed, pilot studies show beneficial effects on inflammatory markers and symptom severity in psoriasis patients (19,20).
14: New strains, Multiple Sclerosis
Two new strains
Microbiome Center is continuously searching worldwide for interesting other substances and strains that you can use in microbiome therapy. We’ve added two new spore-forming probiotic strains to the palette for you to choose from. The first is a Bacillus clausii which, due to its spore-forming properties, is very stable and has excellent gastrointestinal survival (1). This strain has been clinically studied in diarrhea (2,3). There are also tentative indications for a possible effect in uremia (4) and for an inhibitory effect on the pathogenic bacterium Bacillus cereus (5).
The second strain is a Bacillus coagulans. This strain shows a large effect on constipation in a well-performed RCT (6). There are also several clinical studies showing a beneficial effect in IBS (7-9). There is also evidence for a positive effect for the related complaint of abdominal pain, albeit somewhat less consistently (7-12). In addition, there are some indications from clinical studies that this strain is effective in, among others, SIBO (13) and bacterial vaginosis (oral use) (14).
More information about these and all other ingredients can be found in the MC treatment network under the (i) button under the ingredients.
More evidence for the role of the microbiome in multiple sclerosis
There have been several indications that the gut microbiome plays a role in the etiology of multiple sclerosis (MS), such as substances of bacterial origin in the blood and the presence of bacteria in the brains of deceased patients (15). A recently published study adds another clue. In MS patients, immunoglobulin A (IgA) was found in cerebrospinal fluid (16). B cells expressing IgA were also found in the brains of deceased patients, especially at lesion sites. It was striking that the B cells with IgA expression in the cerebrospinal fluid do respond to intestinal bacteria, but not to antigens from the brain. This indicates that these B cells originated from the gut and migrated to the cerebrospinal fluid.
This research suggests that during the active phase of MS B cells that respond to gut bacteria migrate to and are active in cerebrospinal fluid and the brain. It seems plausible that there is an important role for an intestinal barrier here. Immune-modulating probiotic strains may play a role here, and some initial animal and clinical studies of probiotics show initial cautious positive effects (17).
13: Care insurances 2021
Below is a global overview of the reimbursement rules of health insurers for 2021. The common thread boils down to this.
– the larger health insurers have one or more supplementary policies with scope for reimbursement of “alternative medicine”
– the total reimbursement available per year increases with more expensive policies
– often a registered doctor is mentioned as a requirement
– medicines are in principle excluded.
This means that if clients have the correct supplementary policy and have not already drawn up their reimbursement allowance, they can probably count on reimbursement of the costs for consultation and faecal analysis (with the exception of ONVZ), and not for medicine costs. The overview per insurer:
CZ with “additional 5”: €250 per year for alternative and/or psychosocial treatments (€25 per day) and medicines (100%) together
Silver cross with “additional 2 stars” or higher: a maximum of € 40 per day to € 250 per calendar year for alternative care such as orthomolecular treatment
Menzis with “extra care 2” or higher: Maximum of €400 per calendar year (€40 per day for treatments, 100% for medicines) for alternative care
VGZ with “Additional Good” or higher: Alternative care: €200 per year, maximum €40 per day
DSW with “AV Compact” or higher: reimbursement for a doctor’s consultation in naturopathy, a maximum of €25 per treatment date, a maximum of €250 per calendar year
Zorg en Zekerheid with “AV-sure” or higher: reimbursement of treatment by a naturopathic or orthomolecular doctor, a maximum of €250 per calendar year, consisting of a maximum of €25 per day for treatments or 50% reimbursement for medicines
ASR with “Start” or higher: reimbursement for treatment by a doctor, up to a maximum of €100 per calendar year (higher supplement = higher total amount)
ONVZ with “Startfit” or higher: reimbursement of alternative medicine by a doctor, ie consultations and treatments aimed at (curing) a condition. No lab costs. Higher supplement = also reimbursement for registered medicines and a higher total amount.
Ditzo, Anderzorg, Hema, Interpolis and Just do not reimburse alternative medicine.
NB. This overview gives a global impression; no rights can be derived from it.
12: Which strains
Sometimes we are asked which ingredients in our portfolio are available to apply in personal preparations. Therefore, here is a brief overview with a selection of available ingredients:
- For example, the portfolio includes a Clostridium butyricum strain that can make butyric acid, has anti-inflammatory effects, and is effective in, among other things, ulcerative colitis.
- You can also use the well-known yeast Saccharomyces boulardii, which is effective against pathogens and parasites and therefore useful in diarrhoea.
- There is a Propionibacterium freundenreichii strain that produces a. vitamin K2.
- There are specific Bifidobacterium bifidum, brevis, and Lactobacillus acidophilus strains that have been selected for their effect on intestinal permeability reduction and anti-inflammatory effect, and which can reduce insulin resistance.
- One of the ingredients contains the amino acid L-glutamine, which improves the intestinal barrier function and has been studied for reducing the side effects of chemotherapy.
- There is the well-known LGG (Lactobacillus rhamnosus GG) that is effective in IBS and diarrhea, but has also been studied in, for example, mania and ADHD.
In addition to these and other ingredients, we are continuously searching worldwide for interesting other substances and strains that you can use in microbiome therapy:
- We will soon be expanding the portfolio with a Bacillus coagulans and Bacillus clausii strain, for example, which have been studied in vaginosis, IBS, and SIBO.
- We are also working on a Bacillus subtilis and Enterococcus faecium strain that have been jointly investigated in a large number of clinical studies in ulcerative colitis, but also in, for example, respiratory pneumonia.
More information about the available ingredients and references to the literature can be found in the MC treatment network under the (i) button under the ingredients.
Microbiome research in type 1 diabetes
Few will have noticed that Professor Max Nieuwdorp of Amsterdam UMC has received more than a million euros in subsidy from the Diabetes Fund for microbiome research in patients with type 1 diabetes (T1DM) (1). Previous research has already shown that the microbiome of T1DM patients differs from healthy people, partly due to a reduced number of butyric acid-forming bacteria (2,3). In addition, there is some tentative evidence that probiotic use is associated with a lower risk of T1DM and better glycemic control in T1DM patients (4,5). The Amsterdam UMC has already conducted an exploratory study into faecal transplantation in T1DM patients and will publish this this month in the professional journal Gut (1). The award of this grant is a clear confirmation that the increasing insights about the strong relationship between chronic diseases and gut health are valuable for patients and practitioners.
Microbiome in insulin resistance and type 2 diabetes
There are several strong indications that the microbiome plays a role in insulin resistance and type 2 diabetes mellitus (6,7). It is striking, for example, that metformin – the first-line drug in type 2 diabetes – only works when taken orally (8). Metformin appears to act (in part) via the gut and is associated, for example, with an increase in the mucin-metabolizing Akkermansia muciniphila and in butyric acid-forming bacterial species (9-11). Type 2 diabetes and insulin resistance are associated with systemic low-grade inflammation (12). There is some evidence that the metabolic and immune systems are strongly intertwined, presumably because strong defenses are evolutionarily advantageous but require a lot of energy (13). For example, there is evidence that cytokines act directly as metabolic hormones (13). Given the effects that probiotic strains can have on the immune system, but also on intestinal permeability and butyric acid production, it is therefore not unexpected that meta-analyses of RCTs conclude that probiotics can lower, among other things, Hb1Ac and HOMA-IR (14,15).
10: Covid-19, Alzheimer's
Interaction between bacteria and SARS-CoV-2
It is known from various studies and also from RIVM data that obesity, diabetes and cardiovascular diseases increase the risk of a serious course of Covid-19 (1,2). A few weeks ago, an intriguing review (3) appeared in which a synergistic effect is seen between the new coronavirus and lipopolysaccharide (LPS, an endotoxin of bacterial origin). Both decrease the expression of the ACE2 receptor in the lungs, thereby disrupting the angiotensin system. Research with a swine coronavirus has shown that the combination of that virus and LPS leads to severe acute respiratory syndrome (SARS) in pigs, while exposure to each alone produces much milder symptoms. Increased intestinal permeability is also seen in diabetes, among others (4), which leads to increased LPS in the circulation and associated insulin resistance (5). This review (3) is therefore a new indication that improving intestinal barrier function appears to be a useful therapeutic target to protect patients with cardiometabolic diseases.
Mycobiome in Alzheimer’s
Previous studies have already shown that there are differences in microbiome composition between Alzheimer’s patients and healthy individuals (6,7). These studies looked only at bacteria, but the human microbiome is also made up of many other types of microorganisms such as fungi, archea, protists, and viruses. A new publication concludes that there are also differences in the composition of fungi (the mycobiome) in people with mild cognitive decline (8). The researchers also compared the influence of two dietary patterns. Only a modified Mediterranean ketogenic diet appears to affect the mycobiome in patients with mild cognitive decline. This ties in with previous research in which this diet led to improvements in markers of Alzheimer’s disease. Another recent study using an animal model of Alzheimer’s convincingly demonstrates that fecal transplantation from healthy mice to diseased mice leads to reduced deposition of amyloid-β plaques, decreased inflammatory markers, and reduction of cognitive decline (9). These two studies expand the growing body of evidence that the disease process behind Alzheimer’s disease can be influenced via the gut.
9: Migraine, LGG, namechange Lactobacillus
Probiotics for migraine
There are several indications of a relationship between the gut microbiome and migraine (1). A recent systematic review of placebo-controlled studies found two studies that met the inclusion criteria, one of which found a fairly large effect and the other no effect of probiotics (2). It is also known from experience that migraine patients sometimes benefit greatly from probiotics. Some patients who have tried everything report that their migraine attacks have virtually disappeared after they start taking probiotics. A nice example of a study that describes this type of observations in more than 1000 patients is this one, in which the severity of the complaints decreased considerably (3).
New strain: LGG
A new strain has been added to the prescribing portfolio of probiotics: Lacticaseibacillus rhamnosus GG, the world’s most researched probiotic bacterial strain. If you are wondering if there is a spelling mistake in the last name, read the last message in this knowledge flash. The fact that this strain, also known as LGG, has been researched so much (over 1,100 publications in PubMed), certainly doesn’t mean it’s effective for everything. For example, a frequently researched indication is eczema, but a meta-analysis of RCTs shows that the LGG is not effective in this regard (4). We have of course added the LGG because there are various indications where it is effective. In fact, the LGG achieves the highest achievable score for acute diarrhea in our GRADE-based rating system due to two meta-analyses of RCTs with very consistent results (5,6). There is also strong evidence that the LGG is effective in IBS (7.8). Interestingly, LGG has also been studied in ADHD and mania, although these are only preliminary indications (9,10). In addition, there are various other indications, which you can find in the information on our website.
Name change of the bacterial genus Lactobacillus
A few months ago, a team of international experts changed the name of the bacterial genus Lactobacillus (11). This genus contained several known bacterial species, such as L. acidophilus, L. rhamnosus, and L. brevis. For some time there had been indications from, among other things, genetic analyzes that the taxonomic heterogeneity within the old Lactobacillus genus was too great to reasonably group all 261 bacterial species. In the new classification, 23 new genera have been introduced, all of which start with the letter L, so that abbreviations do not change. There are various websites with an overview in which the old and new names can be looked up (12).
8: Microbiome and virus infections
Virus infections are affected by the microtree in various ways, ranging from a stimulant to an inhibitory effect (1). Viruses can make direct use of certain bacterial factors to achieve increased stability, infection rate, and virulence and can be indirectly aided by certain bacteria stimulating expression of regulatory T cells and thereby suppressing the immune system. On the other hand, the microbiome can also prevent viral infections. This can be done directly by binding, absorption, destabilization, and reduced replication of viruses, and indirectly by enhancing the immune response. These opposing effects of the microbiome emphasize the complexity of the host-microbiome interaction and the importance of proper balance. After all, a strong immune response is desirable in viral infections, but after the infection has been conquered, it is precisely the suppression of the immune response that is desired. Stimulation of anti-inflammatory regulatory T cells is also highly desirable in non-communicable diseases (2,3).
Recovery after virus infections
Not only does the microbiome affect viral infections, viral infections also affect the microbiome in multiple ways (1,4). Changes in the gut microbiome have been found in various viruses, including the flu and norovirus. This is linked, among other things, to immune modulation by the virus, but also to changes in food intake during the illness period (5). Disturbances in the gut microbiome after a virus infection are therefore not unexpected, but sometimes they are of a more serious and/or chronic nature. Infectious gastroenteritis, also with a viral cause, can cause the so-called post-infectious irritable bowel syndrome (PI-IBS) (6,7). A disturbed immune activity (including a high level of pro-inflammatory cytokines), a decreased intestinal permeability, and a disturbed gut microbiome play a role in this. In viruses that are mainly active outside the gut, such as Q fever, post-viral complaints such as fatigue also occur and an increased level of pro-inflammatory cytokines plays a role (8). Conversely, Chronic Fatigue Syndrome (ME/CFS) often appears to be viral in origin, again involving a shifted immune activity and disrupted gut microbiome (9,10). Virus infections can therefore have long-term consequences and the immune-modulating role of bacteria in the gut seems to be important in this regard. Unlike during acute viral infections, but similar to non-communicable diseases, the desirable adaptation seems unambiguous: inhibiting the inflammatory activity of the immune system.
7: Immune system
The gut microbiome plays an important role in the education and function of the immune system and acquired immunity (1,2,3). Both antibiotics and probiotics influence the effectiveness of vaccinations (4,5) and the microbiome and certain probiotics influence the course of viral infections (6,7). It is striking that in Covid-19 patients almost one in five patients suffered from diarrhoea, vomiting, or abdominal pain (8) and that the SARS-CoV-2 virus was found in feces and in Dutch sewage (9,10,11). ). In addition, loss of sense of smell is mentioned as a symptom of Covid-19 (12). Intriguingly, this has been linked to the virus’s penetration into the central nervous system, where it may also play a role in respiratory problems via the respiratory center (13,14). The gut-blood barrier and blood-brain barrier are affected by the same factors, and the microbiome plays a role (15,16). Although at first glance the microbiome does not seem to have anything to do with Covid-19, it can indeed play a role and especially immunogenically active bacteria and intestinal barrier function deserve attention.
6: Nervous system and psyche
Microbiome can directly influence nervous system (!)
That there is a relationship between the gut and the brain is not new (1). Since 2014, almost 2000 publications have been published. In February 2020, Nature published research demonstrating a direct link between the microbiome and the nervous system in the gut (2,3). The researchers identified a receptor that is an intrinsic part of the nervous system in the gut and showed that microorganisms in the gut can directly express this receptor (3). This affects functions of the local neural network, such as peristalsis, but through the connection of the vagus nerve, this receptor also provides a direct link between the microbiome and the brain.
Role of the microbiome in autism
There are strong suspicions that autism spectrum disorder is related to gut health. Autistic children often have intestinal complaints such as chronic diarrhea or constipation (4,5) and belong to the group of children most often referred to an MDL doctor (5). In autistic people there is evidence of increased intestinal permeability (6) and elevated levels of an endotoxin of bacterial origin (LPS) are found in the blood (7). A small study with faecal transplantation in autistic children resulted not only in greatly reduced intestinal complaints, but also in significantly improved behavioral scores (8). This effect was still present two years later (9). Recent pilot studies with pre- and probiotics also show tentative improvements in behavioral scores (10,11).
There is a direct link between allergies and the microbiome through the immune system. Allergic responses are IgE mediated and immunological in nature  and the microbiome is known to be involved in the education and tonic of the immune system [2,3]. The relationship with the microbiome is confirmed by different types of studies in asthma, atopic eczema, food allergies, and hay fever [4,5]. Interventions with pre- and probiotics in pregnant women and their children have been shown to have preventive and curative effects in atopic eczema [6,7] and food allergies [8,9]. The effects are strain-specific and this can be translated into the personal preparations MyOwnBlend.
Election of the ‘Lifestyle Professional 2020’
The election of the ‘Lifestyle Professional 2020’ will be held during the congress of the Arts and Lifestyle Association (April 3). This year, in addition to doctors, POHs, pharmacists, lifestyle coaches and dietitians can also be nominated for this. If you have someone in mind, you can report to the association .
Akdis, C.A., Agache, I., 2014. Global atlas of allergy. European Academy of Allergy and Clinical Immunology
Advice Aid; product information update
After some technical challenges, all descriptions and references of the supplements and magisterial ingredients are now completed. You can find these by clicking on the (i) next to a product or ingredient in the Advice Aid or on the Prescription page. The description provides a summary of all studies that have been done with the product or ingredient in question, including the associated references.
The Advice Aid has also been further improved. The proposed quantities of the pharmaceutical ingredients now also take into account the minimum and maximum daily dose for each ingredient. It remains unchanged that the outcome of the Advice Aid is based on the completed scores for the various indications (complaints, medical background, and lab results) on the one hand, and on the strength of the evidence of the products/ingredients for these indications on the other. In the new version of the Advice Aid, a more refined gradation has also been made for the strength of the evidence, which has been weighted in a systematic (GRADE-inspired manner ). We are currently working hard to make the evidence scores visible to you in the next version of the Advice Aid, so that you can even better trace what the advice is based on.
Probiotics may be useful for depression
In recent years, it has become clear that the microbiome plays a role in mood and depression; there is talk of the gut-brain axis. There are relationships with the quality of life ie. depression and the composition, structure, and function of the microbiome [2,3]. Fecal transplantation from patients with major depression disorder (MDD) to mice or rats results in behaviors associated with depression [4,5]. Clinical studies have shown that interventions with probiotics can reduce depression [6-8].
Royal interest in the microbiome
The Palace symposium ‘The Microbiome’ took place on Tuesday 26 November, attended by King Willem-Alexander and Princess Beatrix . Speakers were Martin Blaser, director of the Human Microbiome Program, and Professor Max Nieuwdorp, internist-endocrinologist and pioneer in fecal transplant research. Both lectures can be listened to . At the highest level, too, attention is now being paid to the importance of the microbiome for health.
3: Diet, gut and osteoporosis
The response to food is highly individual
The macronutrient composition of food appears to explain only 16-32% of the glucose response to food, individual factors such as the composition, function and structure of the microbiome are much more decisive. This is evident from the PREDICT-1 study that intensively followed more than 1000 twins and non-twins (https://doi.org/10.1093/cdn/nzz037.OR31-01-19, see the full presentation here).
Irritable Bowel Syndrome (IBS) improves with probiotics and glutamine
Probiotics relieve pain and overall symptom score in IBS (IBS), concludes a meta-analysis of RCTs. However, the effectiveness does depend on the composition (https://doi.org/10.3748/wjg.v21.i10.3072). In many cases there is also increased intestinal permeability with IBS, especially when diarrhea is in the foreground. In those cases, glutamine appears to be effective in IBS (https://gut.bmj.com/content/68/6/996).
Probiotics may be helpful in osteoporosis
The microbiome plays an important role in the gut-bone axis. Animal studies provide first evidence that probiotics have a protective effect against osteoporosis (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710820/). In elderly people with bone fractures, supplementation with probiotics also leads to faster healing of bones and less pain (http://doi.org/10.3920/BM2016.0067).
2: Saccharomyces boulardii
The S. boulardii has a strong evidence base and represents a significant extension of the weapons against various types of diarrhoea, such as antibiotic-associated diarrhoea, travellers’ diarrhoea, or acute and infectious diarrhoea. The S. Boulardii also helps to fight parasites, pathogenic bacteria and pathogenic yeasts, and to reduce inflammation.
This ingredient will be included in the anamnesis and advice aid from now on and the evidence can be found for every indication.
Selection from the literature:
1: Respiratory tract, urinary tract, depression
With the cold, dark and wet months approaching, we have selected these three notions. Respiratory infection Probiotics may reduce the incidence and duration of respiratory infections in children, according to this systematic review of 23 trials involving 6269 children (PMID: 27495104: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979858/ ). Urinary Tract Infection Lactobacillus-containing products may be able to prevent recurrent urinary tract infections in women. The widespread use of antibiotics has led to an increase in E. coli-resistant isolates in urinary tract infections worldwide. A promising non-antibiotic approach is the use of probiotic lactobacilli (PMID: 29602464; https://www.ncbi.nlm.nih.gov/pubmed/29602464 ). Depression Probiotics appear to reduce susceptibility to depression. Impaired gut barrier function and inflammation are correlated with depressive symptoms. This is discussed in several publications, such as a clinical study on the effect of consumption of probiotic supplements on depressive symptoms in a sample of participants with mild to severe depression (PMID: 31078831; https://www.ncbi.nlm.nih.gov /pubmed/31078831 ).