How can flavonoids improve gut health?
How can flavonoids improve gut health?
Flavonoids are important polyphenols that can exert beneficial effects in the body. Due to their antioxidative properties and metabolism, they can improve gut health and change the gut microbiome. In this article, we will describe how flavonoids, and especially hesperidin and naringin, can change the gut microbiome composition, increase gut barrier function, enhance the immune system, and altogether improve gut health.
What are flavonoids?
Flavonoids are a group of phytonutrients (chemicals of plants) that are found in almost all fruits and vegetables. Flavonoids give color to fruits and vegetables, but are also found in cacao, coffee and tea. There are more than 6,000 types of flavonoids.
Since there are many types of flavonoids, they also have a wide range of beneficial effects, such as reducing chronic inflammation, and reducing risks associated with cancer and cardiovascular diseases (1, 2). Thus, implementing different flavonoids in your daily diet could be beneficial your health.
Flavonoids and gut health
Gut health and the gut microbiome have gained a lot of interest in the past years, since the gut microbiome and its metabolites are recognized as important regulators of host health.
The gut barrier is an important barrier because it acts as a physical defence against toxins and microorganisms. This barrier should remain intact to function properly.
Flavonoids may improve intestinal barrier function via inhibition of inflammatory proteins such as nuclear factor-kappa B (NF-κB), and via reduction of oxidative stress.
Flavonoids also contribute to the preservation of the intestinal tight junction barrier and structure, which is important for remaining the physical barrier for pathogens (3).
Flavonoids can stimulate short chain fatty acids to increase gut health
Additionally, it is found that flavonoids can increase faecal short chain fatty acids (SCFAs), which may be a result of increased SCFA production in the gut. SCFAs have different beneficial effects for the host and gut health. These benefits include serving as energetic fuel for intestinal epithelial cells, and improving intestinal barrier function (4, 5).
An important SCFA for gut health is butyrate. It can bind to G-protein coupled receptors. Upon binding, different anti-inflammatory signalling pathways can be promoted in macrophages and dendritic cells, which are important cells in the immune system of the colon (6).
Thus, flavonoids can increase gut barrier function and SCFA production, and potentially enhance the immune system via butyrate. Therefore, they are beneficial for gut health and it’s also shown in human studies that they can be used for inflammatory bowel diseases! (3)
Two flavonoids for gut health; What are hesperidin and naringin?
Hesperidin and naringin are flavanones , a subclass of flavonoids. These flavanones are mostly present in freshly prepared juices of citrus fruit, such as grapefruit, oranges and lemons. But it’s worth noting that hesperidin can be obtained in higher concentrations than naringin. Both compounds are even more abundant in the peels of these citrus fruits.
After oral consumption, hesperidin and naringin reach the colon almost completely intact, because they are difficult to degrade by the enzymes in the stomach and the small intestine.
This means the gut microbiota can digest them. They do this by releasing α-rhamnosidase, which converts hesperidin and naringin to hesperetin and naringenin. These metabolites are more bioavailable to the body, resulting in higher uptake by the gut into the blood, meaning they can be used by other tissues (7).
Hesperidin and naringin can feed specific bacteria, meaning they can influence the microbiome. It was shown that naringin could reduce microbial dysbiosis caused by high fat diet in mice. This means that harmful bacteria were reduced and there was an increase in beneficial bacteria (8). The same was shown for hesperidin in rats (9).
Hesperidin and naringin also play a role in immune system regulation. They can inhibit gut inflammation and oxidative stress by increasing antioxidant levels. By bringing gut inflammation down, the gut barrier stays intact as a physical defence against pathogens.
That hesperidin and naringin reduce gut inflammation was not only shown for them individually, but also when they were combined in mice.
Hesperidin and naringin: Hero flavonoids of MicrobiomeX®
Hesperidin and naringin are the focus of many clinical trials done by BioActor, as the product MicrobiomeX® is a natural extract from Citrus sinensis & paradisi, consisting of both flavonoids.
In vitro simulations of the human colon with the TIM-2 system showed that MicrobiomeX® could increase butyrate producing bacteria Roseburia spp. and acetate producing bacteria B. eggerthii (9). As mentioned before, butyrate is an important SCFA for gut health.
Besides in vitro studies, there have also been done clinical trials on the butyrate increasing properties of MicrobiomeX®. All clinical trials are available in the MicrobiomeX® White Paper.
It has also been found that by consumption of MicrobiomeX® calprotectin levels went down, which could indicate that MicrobiomeX® helps to bring gut inflammation down.
MicrobiomeX® combines the benefits of the flavonoids hesperidin and naringin and is therefore an ideal ingredient for gut health. Do you wish to read more about the studies described in this blog? Download our whitepaper on MicrobiomeX® below.
Short-chain fatty acids and their importance to gut health
Short-chain fatty acids and their importance to gut health
Short-chain fatty acids are saturated fatty acids that play an important role in gut health. They have several functions in human metabolism. Increasing the level of short-chain fatty acids in the gut might be a beneficial strategy to support overall health. Consumption of prebiotics and/or postbiotics can lead to higher levels of short-chain fatty acids.
What are short-chain fatty acids?
The gut microbiome is the community of microorganisms that can be found living in the gut. Evidence that bacteria in the gut are important to your health is growing each day. That’s why it is important to have a good balance of different bacteria in the gut. Not having a well-balanced microbiome is an indicator for several health issues, such as obesity (1).
The bacteria in the gut partially fulfill their role in health by making short-chain fatty acids (SCFAs). SCFAs are saturated fatty acids that contain six or fewer carbon molecules.
SCFAs are produced by the microbiota when they break down dietary fibers and resistant starches that are not metabolized by the body. To break these substrates down, the microbiota do not need oxygen, which is why this process is called anaerobic fermentation.
The most important SCFAs that are produced in the gut are acetate, propionate, and butyrate, and all of them have different effects on gut health (2).
Following the production of SCFAs by microbiota, they are taken up by the first layer of gut cells. They are used directly as fuel by these gut cells and if the colonocytes don’t metabolize them, they are used elsewhere, for example as an energy source for liver cells (3).
The benefits of short-chain fatty acids
Other than being fuel for different types of cells, SCFAs have a beneficial effect on your gut health.
Short-chain fatty acids maintain the intestinal barrier
One of the benefits of SCFAs is that they help maintain the intestinal barrier. The intestinal barrier is important because it forms a layer of cells that separates the inside of your body from everything that passes through your gastrointestinal tract.
The structural integrity of the gut wall is key, as pathogens (e.g., viruses, bacteria, and toxins) can enter the body if there are gaps between cells of the gut wall.
SCFAs help preserve the intestinal barrier by feeding the cells of the gut wall and by stimulating the dilation of blood vessels, resulting in more blood flow to these cells. This is positive as the cells will get more oxygen.
Short-chain fatty acids increase mucus production in the gut
SCFAs have also been shown to increase mucus production in the gut. Mucus is a slimy substance that forms a protective layer on your gut wall.
An increase in mucus production is beneficial since the protective layer between the intestinal cells and the contents of your gut will be thicker. The thicker the better, meaning that this improves the function of the mucus and decreases the risks of pathogenic infiltration (3).
Short-chain fatty acids reduce gut inflammation
Gut inflammation is often seen in older people or people with irritable bowel syndrome. SCFAs help bring this inflammation down by altering the DNA expression of gut cells.
The result of this alteration is a decrease in the release of chemokines, which are signaling proteins that are usually involved in white blood cell attraction. Reducing the recruitment of white blood cells is an anti-inflammatory action (4).
Short-chain fatty acids can induce satiety
Researchers have demonstrated that SCFAs are able to modify food intake by promoting satiety and the SCFA responsible for that is propionate, which is also produced by the gut bacteria.
Propionate is transferred to the liver where it can bind to specific receptors and this leads the liver to start making gut hormones that induce satiety and thus lower hunger (5).
In short, SCFAs are relevant for gut health, but for overall health as well, which means it is valuable to raise the level of SCFAs in the gut. One way to achieve a higher level of SCFAs is by consuming prebiotics and, less familiar to most people, postbiotics.
What are prebiotics?
Prebiotics are non-digestible food ingredients that have a health benefit to the host. There are different types of prebiotics, and they have several health benefits. These health benefits range from supporting your immune system to providing energy to microbiota that help maintain gut health.
Prebiotics are food compounds, such as fibers and starches, that are not digested by the human digestive system. This means that the prebiotics reach the gut and the microbiota while still intact. The microbiota can digest them, leading to the creation of substrates that can be useful for human health.
How can prebiotics lead to higher levels of short-chain fatty acids?
Prebiotics go through anaerobic fermentation, which results in SCFA production. This means that taking prebiotics can help increase SCFA levels in the gut. As we have mentioned above, there are several reasons why you would want this!
There are several food products that contain high levels of prebiotic fibers, but it is also possible to increase prebiotic intake by taking supplements.
One example of a prebiotic fiber food is chicory root. It contains high amounts of prebiotic fiber inulin. Other good foods are arabinoxylan rich foods, such as wheat, corn, rice and oat. Arabinoxylans have a lot of health benefits and they have strong prebiotic properties.
The downside of prebiotics is that everyone has a different microbiome composition, which means that everyone also experiences different outcomes of prebiotic consumption.
For this reason, research has been done on alternatives. This led to an increase in interest in something that is more unknown than prebiotics, namely postbiotics.
Postbiotics are bacterial products, meaning that they aren’t fermented by the gut microbiota after consumption. An example of postbiotics are different short-chain fatty acids, as these are products of the microbiota.
Do you want to know more about postbiotics? Read this article.
How can MicrobiomeX® support SCFA levels?
MicrobiomeX® is an ingredient based on citrus flavonoids that can boost the immune system and improve gut defense. It has several ways to boost gut health and your immune system.
One way MicrobiomeX® helps is by promoting the growth of butyrate-producing strains of bacteria in the gut. Among these are the Faecalibacterium prausnitzii, Clostridium leptum and Roseburia. As mentioned before, butyrate is a SCFA that has several health benefits on the host.
Want to read more about MicrobiomeX®? Click here!
The benefits and challenges of synbiotic dietary supplements
The benefits and challenges of synbiotic dietary supplements
In the last years, synbiotic supplements have emerged as an interesting approach to improve gut health. Instead of using only pre- or probiotics, synbiotic products combine both. There are two types of synbiotics, namely complementary and synergistic synbiotics. Currently, most of the synbiotics on the market are complementary products since the formulation and research of synbiotics are quite challenging. In this article, we will explain synbiotic supplements in more detail, including the benefits and formulation challenges.
What are synbiotic dietary supplements?
The international scientific association for Probiotics and Prebiotics (ISAPP), defines synbiotics as: “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host” (1).
There are two types of synbiotic products: complementary and synergistic synbiotics. Complementary synbiotics are the most found on the market. This type should contain pre- and probiotic compounds that clinically show a health benefit together, but also when used independently from each other. Hence, they do not have to interact with each other.
On the other hand, synergistic synbiotics do not necessarily contain pro- or prebiotic compounds. Instead, they should contain microorganisms and substrates that are selectively utilized by the provided bacteria in the product. In this case, the combination should have a greater beneficial effect than the microorganisms or substrates independently (2).
Curious to know about prebiotics? Find out more!
What are the benefits of synbiotic dietary supplements?
Pre- and probiotic products can have beneficial effects on gut health, immune function and the production of beneficial metabolites such as short-chain fatty acids. Synbiotic products could have the same health effects, and they potentially decrease cardiovascular risk factors, markers of insulin resistance and prevalence of metabolic syndrome as well (3).
Furthermore, synbiotic formulations must contain living bacterial strains and the substrates that can be used by these bacterial species specifically. In this way, the species have the chance to feed themselves, proliferate, and adhere to the intestinal wall of the host.
Another advantage of such synergistic dietary supplement formulations, is that they could address the “responder/non-responder” phenomenon (2).
The “responder/non-responder” phenomenon means that some subjects respond to a pre- or probiotic product, whereas others do not experience any beneficial effect. The difference could be caused by the fact that everyone has a unique microbial composition in the gut and therefore reacts differently to the treatments.
By providing the bacterial strains and their substrates simultaneously, the supplied bacteria will have an advantage compared to other bacterial strains that were already present in the gut, since they already have their selectively fermentable substrate to grow on. They could subsequently outcompete some resident microbial strains and establish a niche in the gut.
In other words, the substrate serves as a sort of fertilizer for the supplied bacterial strains and increases the chance that the bacterial strain will colonize and establish in the gut. In this way, it may be more likely that a subject will respond to the supplement or product and experience a beneficial effect!
The main challenges in formulating synbiotic dietary supplements
Although synergistic synbiotics have a lot of potential, formulating them comes with some challenges:
- Prebiotics or substrates often need to be consumed in larger amounts to have a beneficial effect, which may go along with gastro-intestinal complaints such as feeling bloated or flatulence. To limit these complaints, prebiotics may be added in lower doses, risking the loss of their beneficial health effects.
- Microorganisms are highly sensitive to the environment, which makes it difficult to store the synbiotic products under many circumstances.
- The water activity of the substrate: Water activity is a measure of water in a product that is available to react with or attach itself to other material, also known as ‘free’ water. Products with a higher water activity are more likely to be affected by bacteria and fungi. Therefore a substrate with a low water activity should be chosen (4).
Besides formulation challenges, researching the synergistic synbiotic effects comes with some difficulties.
The synbiotics that are now often used in studies have been formulated based on criteria such as shelf life, cost, and availability, rather than on metabolic, functional or other characteristics of the microorganisms or substrates.
In most studies, Lactobacilli and Bifidobacteria are included as the probiotic component and inulin, various oligosaccharides, or dietary fibres are chosen as prebiotic ingredient, yet only one human trial showed beneficial effects (5, 6).
To screen for new promising synbiotics, in vitro studies will first be performed because clinical trials are very expensive and time-consuming. In vitro models simulating the lower and upper gastrointestinal can be helpful, such as the TIM1 and TIM2 model. The TIM-2 model is a dynamic gastrointestinal model, which is used for in-vitro research.
These models can be used to assess the survival of a probiotic through the gastrointestinal tract and the effect of synbiotics on gut microbiota.
MicrobiomeX®: the ingredient of choice for your synbiotic formula
To limit the gastro-intestinal complaints caused by high dosages of substrates, other substrates that have beneficial effects in lower dosages, such as polyphenols, could be used. The polyphenols can be transformed into bioactive molecules or into metabolites that can be used by other microorganisms, eventually resulting in a health benefit for the host.
MicrobiomeX® is a first-in-class Flavobiotic® researched and developed by BioActor. It is a natural ingredient from citrus, consisting of two active flavanones: hesperidin and naringin. BioActor combined these two powerful phenolic compounds in a unique complex ideal for the formulation of synbiotic dietary supplements in doses ranging from 250 to 500 mg.
Thanks to its proven high stability in combination with probiotics and its low water activity, MicrobiomeX® is an ideal ingredient to formulate synbiotic dietary supplements. Specifically, MicrobiomeX® can be used as a substrate, and can be metabolized in the gut by bacteria possessing the ramnosidase enzymes such as Lactobacillus acidophilus LA-5, Lactobacillus Brevis and B. animalis ssp. Lactis (7).
After being metabolized, not only does MicrobiomeX® promote the growth of beneficial bacteria in the gut, but the active metabolites that are released in the gut exert a direct antioxidant and anti-inflammatory effect resulting in improved overall gut health.
MEET US - BioActor Presenting MicrobiomeX® and Naxus® at the 15th Annual IPC conference
MEET US – BioActor Presenting MicrobiomeX® and Naxus® at the 15th Annual IPC conference
Press release
The 15th International Scientific Conference on Probiotics, Prebiotics, Gut Microbiota and Health – IPC2022 will be held during 27 – 30 June 2022 in Bratislava. BioActor is an active contributor and confirmed partner of this conference. Hans van der Saag (CEO) will present on our ingredient Naxus®, a prebiotic with metabolic and immune effects, and Yala Stevens (CSO) presents the clinical and mechanistic research on MicrobiomeX® in irritable bowel syndrome (IBS) patients and elderly subjects.
BioActor Presenting MicrobiomeX® and Naxus® at the 15th Annual IPC conference
The 15th International Scientific Conference on Probiotics, Prebiotics, Gut Microbiota and Health – IPC2022 will be held during 27 – 30 June 2022 in Bratislava.
The IPC conference is the world’s biggest scientific conference that focuses solely on basic and applied research of probiotics, prebiotics, gut microbiota and health. More than 400 scientists from over more than 80 countries have attended the conference last season.
The scientific program will focus on current advances in the research, production and use of probiotics and prebiotics with particular focus on their role in maintaining health and preventing diseases. At IPC, leading scientists from industry and academia present current advances in understanding and influencing the interaction between gut microbiota and human health.
The conference enables the interactive exchange of state-of-the-art knowledge. It is focused on evidence-based benefits, health claims proven in scientific experiments and clinical trials.
BioActor is an active contributor and confirmed partner of this conference. Hans van der Saag (CEO) will present on our ingredient Naxus®, a prebiotic with metabolic and immune effects, and Yala Stevens (CSO) presents the clinical and mechanistic research on MicrobiomeX® in irritable bowel syndrome (IBS) patients and elderly subjects.
Naxus® presentation by Hans van der Saag (CEO)
Naxus® is a native arabinoxylan extract from the wheat endosperm. It is a powerful and well-tolerated prebiotic with metabolic and immune effects. Due to its complex branched structure, Naxus® is slowly and selectively fermented by multiple species of the microbiota, inducing a remarkable bifidogenic effect without causing gas formation and intestinal discomfort. It induces a remarkable microbiota shift and increased short-chain fatty acids production, with proven effects on immune health and glycemic control.
MicrobiomeX® presentation by Yala Stevens (CSO)
MicrobiomeX® is a natural extract from citrus fruit designed to beneficially modulate the microbiome composition in the gut. It’s a first-in-class Flavobiotic® that protects the gut barrier and directly leverages the gut microbiome’s potential. This results in enhanced immune health, as well as anti-inflammatory effects.
IBS is a functional gastrointestinal disorder with various symptoms including pain and discomfort in the abdomen. Also, elderly often develop imbalances in their gut microbiota and often experience discomfort.
Patients with IBS and elderly would benefit substantially from treatments that could relieve their symptoms and improve their gut health. The flavonoids in MicrobiomeX® have the potential to benefit individuals with gastrointestinal conditions because of its antioxidant and anti-inflammatory properties.
Business opportunities
The IPC conference is a great opportunity to reconnect with colleagues from all over the world and make new contacts. Hans van der Saag (CEO) and Yala Stevens (CSO) will be there to represent BioActor’s portfolio, with a focus on our gut health ingredients. Feel free to pass by at any time to chat about our innovative ingredients for gut health support!
We look forward to meeting you in Bratislava!
The IPC 2022 conference will take place from 27 to 30 June 2022.
Where: Hviezdoslavovo námestie 3, 811 02 Bratislava, Slovakia
About BioActor
BioActor, based in Maastricht, Netherlands, is a product development company that supplies proprietary bioactive formulations to the nutrition & healthcare industry. The company focuses on the development of innovative bioactives that address active living and healthy ageing. The goal is to provide the nutrition & healthcare industry with science-based innovations that confer a real health benefit to the consumer.
For further information, see www.bioactor.com or visit https://microbiomex.com/ or https://naxus.nl/
MicrobiomeX® nominated as finalist for 2022 NutraIngredients-USA ‘Ingredient of the Year’
MicrobiomeX® nominated as finalist for 2022 NutraIngredients-USA ‘Ingredient of the Year’
Press release
BioActor is delighted to share that MicrobiomeX® was nominated as a finalist for the 2022 NutraIngredients-USA ‘Ingredient of the Year’ in the category Prebiotic. NutraIngredients-USA Awards honour the best and brightest in ingredients, finished products, companies, people and initiatives in the nutrition and dietary supplements industry.
Finalist for 2022 NutraIngredients-USA ‘Ingredient of the Year’
We are excited to announce that MicrobiomeX® was nominated as a finalist for the 2022 NutraIngredients-USA ‘Ingredient of the Year’ in the category Prebiotic.
The NutraIngredients brand has led the online news source in the nutrition industry for over 19 years, providing insights into the functional food and supplement market in North America, ranging from investments and innovation to ingredients, product formulation, regulation, consumer trends and more!
Specifically, NutraIngredients-USA Awards honour the best and brightest in ingredients, finished products, companies, people and initiatives in the nutrition and dietary supplements industry. With a focus on innovation, long-term market success and state-of-the-art research, it is an honour that MicrobiomeX® was nominated a finalist!
MicrobiomeX® is a first-in-class Flavobiotic® that has been clinically proven to improve the SCFA profile, lower gut inflammation and enhance immunity through its precision prebiotic effect. Beneficial changes in the microbiota are induced at a low dose of 250-500 mg, and MicrobiomeX® is stable with probiotics.
“Special thanks goes out to our US distributor SEPPIC with whom we collaborated to get there”, says Joris Kretzers, Sales Manager Western Europe & North America of BioActor. “We are very proud of this achievement and are looking forward to the winner announcement in July!”
About BioActor
BioActor, based at the Maastricht Health Campus, Netherlands, is a life science company that has developed a range of proprietary bioactive ingredients for the nutrition & consumer health industries. The company focuses on the development of plant-based health ingredients for active living and healthy ageing. The goal is to provide the nutrition & consumer health industries with clinically tested innovations that confer a real health benefit to the consumer.
Feel free to contact BioActor via info@bioactor.com for more information on the possibilities MicrobiomeX® has to offer.
Further information can be found on: www.microbiomex.com and www.bioactor.com
Can Prebiotics and Probiotics help relieve IBS symptoms?
Can Prebiotics and Probiotics help relieve IBS symptoms?
Prebiotics and probiotics are an interesting topic for people with gastrointestinal disorders, including irritable bowel syndrome (IBS). Researchers have conducted various studies regarding their influence on improving IBS symptoms. In this article, we will explain the different types of IBS and how prebiotics and probiotics may be beneficial in managing this chronic long-term condition.
What is IBS?
Irritable bowel syndrome (IBS) is a chronic condition that affects the quality of people’s lives and includes symptoms such as abdominal pain or discomfort, bloating, gas, constipation, and diarrhea [1].
Some studies have estimated that more than 9% of the worldwide population suffers from IBS, with women 1.5 to 3 times more likely to experience IBS symptoms [2].
To date, IBS causes are still unknown and some possible factors that are responsible for IBS, include physiological disturbances, genetics, and digestive motility [3]. Based on the abnormal manifestation of the bowel movements, IBS has four subtypes [4, 5].
- IBS-C: Constipation prevailing
- IBS-D: Diarrhea predominant
- IBS-M: Mixed of Constipation and Diarrhea
- IBS-U: Unspecified when a patient does not belong to one of these categories
Probiotics and IBS
Although the causes of IBS are still unknown, it has been suggested that an imbalance of the gut microbiota can be responsible for IBS development.
Probiotics are live microorganisms that confer a health benefit on the host by decreasing the harmful bacteria and supporting the gut’s natural bacteria [6]. If you want to increase the good bacteria in your body, various fermented foods and supplements include probiotics.
As it concerns food, a few suggestions might be yoghurt, tempeh, kombucha and kimchi , while supplements usually include beneficial strains like Saccharomyces Boulardii, Bifidobacterium Bifidum, Bifidobacterium Lactis, Lactobacillus Acidophilus, and Lactobacillus Plantarum.
Research has shown that IBS symptoms can be improved by the daily consumption of Probiotics, even if the exact mechanism is still not completely understood [7]. Probiotics can act in different ways depending on the type of IBS and other factors such as age and gender [8].
It is proposed that Probiotics may improve IBS symptoms by [9]:
• Inhibiting the colonisation of pathogens in the gut
• Enhancing the gut barrier function
• Boosting the immune system
• Improving digestive functions
• Reducing inflammation in the gut and gas formation
What are prebiotics?
Prebiotics are usually non-digestible fibre compounds that are fermented by the gut microbiota, stimulating the growth and/or activity of beneficial bacteria (probiotics) in the gut [10]. To classify these compounds as prebiotics, they need to comply with three requirements [11]:
• be non-digestible and resistant to breakdown by stomach acid and enzymes in the human gastrointestinal tract
• be fermented by living microorganisms in the gut
• stimulate the growth and/or activity of beneficial bacteria (probiotics)
It is possible to combine prebiotics with probiotics to create synbiotic dietary supplements. You can read more about that here.
Prebiotics and IBS
Research into the role of prebiotics in managing IBS symptoms is conflicting and shows that the beneficial effect may be subjective and depend on the IBS and type.
For example, some studies found that soluble fibres such as psyllium and inulin may provide significant pain relief for IBS patients with constipation and/or diarrhoea. In contrast, other studies found that the effect is limited.
Prebiotics act by stimulating the growth of a bacterium that produces lactic acid called Bifidobacterium. Interestingly, Bifidobacterium has been associated with improved gastrointestinal symptoms in people with IBS. More specifically, this genus lowers the pH to desirable levels for beneficial microbes and undesirable levels for pathogenic bacteria
[12].
The consumption of specific prebiotics such as arabinoxylans from wheat (AX) can increase the amount of Bifidobacterium in the colon.
In addition, there are also molecules with known prebiotic activity, such as citrus-derived flavonoids. Research has shown that these compounds can reach the colon without being digested and are metabolised by the gut microbiota, stimulating the growth of beneficial bacteria..
These prebiotic flavonoids are different from prebiotic fibres because they are not fermented but rather deglycosylated by the gut microbiota. Furthermore, their ability to work at low doses is associated with their high tolerance as opposed to fibres. Finally, the lack of fermentation avoids gas formation and the resulting feeling of bloating and flatulence.
Multiple studies have shown better protection of gut mucosa against colonisation by pathogens and viruses. Also, citrus flavonoids allow greater production of short chain fatty acids (SCFA) like butyrate and propionate, important compounds for the immune system and metabolic functions.
The bottom line
IBS is a chronic condition that affects a large part of the world’s population.
There is no known cure for this condition, but there are many treatment options to reduce or eliminate symptoms, such as dietary modifications, lifestyle changes, and prescription medications.
In many cases, probiotics and prebiotics may be beneficial in managing the IBS symptoms. However, the beneficial effect is subjective and depends on the IBS type. Therefore, it is essential to understand how dietary changes and supplementations affect the symptoms.
New in vitro co-culture model study published with citrus flavonoid extract MicrobiomeX®
New in vitro co-culture model study published with citrus flavonoid extract MicrobiomeX®
Press release
British Journal of Nutrition has recently published a new in vitro co-culture model study with a citrus flavonoid extract MicrobiomeX® and its metabolites, hesperetin and naringenin. The novel publication suggests that these citrus flavonoids, as well as their metabolites, may reduce intestinal inflammation.
New in vitro co-culture model study published with citrus flavonoid extract MicrobiomeX®
MicrobiomeX® is a first-in-class Flavobiotic® developed by BioActor, that combines active ingredients from Citrus sinensis and Citrus paradisi. MicrobiomeX® has already been studied and reported to have various beneficial effects on the gut and immunity. MicrobiomeX® consists of standardised citrus flavonoids, that form active metabolites, hesperetin and naringenin, in the gut after being deglycosylated by the gut microbiota.
In the recently published in-vitro study, a validated co-culture system of Caco-2/THP-1 cells as model for intestinal inflammation and cytokine-induced barrier disruption was used to determine the effects of citrus flavonoids and their metabolites on intestinal inflammation.
During the research, cells were treated with citrus flavonoids, their metabolites, or a vehicle control. Additionally, cells were incubated with lipopolysaccharide (LPS), which is known to induce inflammation and deterioration in epithelial integrity.
The conclusion highlights that hesperetin and naringenin significantly reduced NF-kB activity, leading to a reduction in intestinal inflammation. Pro-inflammatory cytokines IL-8, TNF-α and IL-6 were also significantly reduced after hesperetin and naringenin administration.
The mechanism behind this reduction in inflammation can be ascribed to partial inhibition of the NF-κB signalling pathway.
“We are very happy with the results of this study, as we were able to show that both the citrus flavonoids themselves and their metabolites are able to reduce inflammation in the intestine”, says Yala Stevens, CSO of BioActor. “These new scientific insights on MicrobiomeX® will allow us to consolidate its applications to products targeting gut health and immune function”.
About BioActor
BioActor, based at the Maastricht Health Campus, Netherlands, is a life science company that has developed a range of proprietary bioactive ingredients for the nutrition & consumer health industries. The company focuses on the development of plant-based health ingredients for active living and healthy ageing. The goal is to provide the nutrition & consumer health industries with clinically tested innovations that confer a real health benefit to the consumer.
Feel free to contact BioActor via info@bioactor.com for more information on the possibilities MicrobiomeX® has to offer.
Further information can be found on: www.microbiomex.com and www.bioactor.com
What is the TIM-2 system? An in-vitro model of the colon
What is the TIM-2 system? An in-vitro model of the colon
The TIM-2 model is a dynamic gastrointestinal model, which is used for in-vitro research. The TIM-2 model can be used to study changes in the microbiota composition and the production of beneficial molecules in the gut. It resembles the human large intestine, including peristalsis, dialysis, and microorganisms. It is a good model that provides short experiment durations and the studies done with it are highly reproducible.
What is the TIM-2 model?
The TIM-2 (TNO in-vitro) model is a computer-controlled dynamic in-vitro gastrointestinal model of the colon used in research to study changes in the microbiota composition.
This model closely mimics part of the human large intestine, including its microorganisms, peristaltic movements, temperature (37ºC) and acidic pH (5.8).
What is the TIM-2 model used for in research?
The TIM-2 model has a wide range of applications in research. It can be used to study changes in the microbiota composition and production of beneficial molecules such as short-chain fatty acids associated with specific dietary patterns or ingredients and, consequently, to increase human health through the understanding of microbiota.
Due to the health benefits of short-chain fatty acids (SCFA), many studies have focused on carbohydrate fermentation and the subsequent production of SCFA.
However, it has also been used to study the effects of probiotics after antibiotic treatment, fermentation of prebiotic fibres, metabolization of molecules such as flavonoids and even to investigate the differences in microbiota from lean and obese individuals.
Watch the interview with prof. Koen Venema
Difference between TIM-2 model and other in-vitro models
Compared to other in-vitro models, TIM-2 holds some unique features, which allow predicting what would happen in an actual clinical trial.
The way the peristaltic movements are produced in the TIM-2 model gives a better mixing of the components than what would be accomplished by stirring or shaking. Thanks to this, in TIM-2 there is no phase-separation of solids and liquids, which is what occurs in other models.
On the other hand, in vivo microbial metabolites are normally taken up by the gut epithelium. This is, of course, not possible in an in-vitro model, but the TIM-2 model features a unique dialysis system that removes these metabolites produced by microorganisms.
The accumulation of these microbial metabolites would otherwise result in the inhibition or death of the microorganisms present in the model. Therefore, the dialysis system allows maintaining a highly active microbiota, with a similar density to that found in the human intestine.
In other systems, metabolites tend to accumulate. In fact, with the TIM-2 model, since all the microbial metabolites are collected, they can be measured, which is something not possible in a real-life setting.
What are the advantages and limitations of the TIM-2 model?
Advantages of the TIM-2 model include:
• Short experiment duration. Compared to other models, experiments are quick, usually taking three test days or even less.
• Presence of peristaltic movements and dialysis system. These two unique features allow predicting what would happen in an actual clinical trial.
• Single parameter study. If a single parameter in the system is changed, the effect of that parameter on the microbiota can be studied.
• Highly reproducible. Since the model is computer-controlled, it is highly reproducible.
Like other in-vitro models, the TIM-2 model has some limitations, which include:
• Absence of gut epithelial cells, immune cells and neurons. However, samples can be taken and incubated with these kinds of cells to investigate interactions.
• Based mostly on healthy individuals. The model has been developed based on data coming from mostly healthy individuals. For this reason, it is unclear exactly which parameters to adjust when simulating patient populations.
• Absence of feedback mechanisms. Due to this, as with similar in-vitro models, the results will always be an indication of what may occur in real life and, therefore, they should be interpreted carefully.
Three ways MicrobiomeX® supports your immune system
Three ways MicrobiomeX® supports your immune system
The knowledge about gut microbiota and its connection with the immune system is increasing every day and so is the consumption of science-based products helping consumers achieve their immunity goals. MicrobiomeX® is a nutraceutical ingredient based on citrus flavonoids that can boost your immune system by improving the gut microbiota composition stimulating the production of butyrate, increasing the level of antibody SIgA, and lowering the level of intestinal inflammation.
The connection between gut microbiota and immune system
Every day the body is exposed to different pathogens that can potentially cause disease. The immune system can protect the body from these intruders and the gut microbiota plays a crucial role in doing so.
The microbiome consists of a collection of bacteria living in your gut. Primarily, the good bacteria residing in the intestine adhere to the gut wall. Once the gut wall is full of these bacteria, other pathogens cannot adhere. In this way, beneficial bacteria prevent bad bacteria from “sticking” to the gut mucosa [1].
Moreover, these bacteria produce important molecules such as short-chain fatty acids (SCFA) that are involved in improving immune function and lowering gut inflammation.
What is MicrobiomeX®?
MicrobiomeX® is an ingredient based on citrus flavonoids that can boost the immune system and improve gut defense.
BioActor developed MicrobiomeX® and, together with Maastricht University and Wageningen University, researched the ingredient and confirmed its health benefits in multiple clinical, ex-vivo and in-vitro studies.
Clinical research in different study populations has shown that MicrobiomeX® has a direct effect on gut health and immunity by being metabolized by gut microbiota and positively changing the microbiota composition. This is what we call Flavobiotic® effect.
MicrobiomeX® is standardize for two important citrus flavonoids: hesperidin (>85%) and naringin (>5%)
The Flavobiotic® effect and immune boosting effects have been demonstrated at low dose from 250mg to 500mg in a dose dependent fashion.
Three ways MicrobiomeX® supports your immune system
If you are considering including MicrobiomeX® in your formulation, you should know this:
1. MicrobiomeX® positively changes the microbiota composition helping stimulate the production of butyrate.
When health-promoting bacteria are present in the gut, they help protect your gut wall from pathogens and bad microorganisms. MicrobiomeX® has been shown to help the growth of beneficial microbiota in the gut, for example strains that belong to the phylum Firmicutes.
Not only helps MicrobiomeX® with maintaining a protective layer against bad microorganisms, but it also promotes butyrate-producing strains such as Faecalibacterium prausnitzii, Clostridium leptum and Roseburia. This results in higher levels of butyrate [2].
This is beneficial, mainly because butyrate inhibits nuclear factor κB (NF-κB). Dysregulation of NF-κB is often seen in inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis. This means, that by increasing butyrate levels in the gut and consequently inhibiting NF-κB MicrobiomeX® helps lower inflammation in the gut [3].
2. MicrobiomeX® increases Secretory Immunoglobulin A
After four weeks of daily 500 mg MicrobiomeX®, fecal Secretory Immunoglobulin A (SIgA) significantly increased in healthy elderly.
Why is this good news?
IgA is the antibody that is the most produced by the body and it is primarily found in the gastrointestinal system, where it plays a big role in keeping your intestinal microbiota in check. IgA directly binds to pathogens such as bad bacteria and viruses and neutralizes them.
Neutralization of pathogens stops them from colonizing the mucosal layer of the gut wall and infiltrating the cells of the gut to cause illness. This protection mechanism is known as ‘immune exclusion’ and makes SIgA a key factor in your immune system.
3. MicrobiomeX® lowers gut inflammation
Consumption of MicrobiomeX has shown to lower calprotectin levels. Calprotectin is found in different parts of the body, and it is an indicator of chronic inflammation.
Typically, older people and people with irritable bowel syndrome or leaky gut syndrome have chronically increased levels of calprotectin [4].
Gut inflammation leads to a lesser functioning gut barrier, which makes it easier for pathogens to infiltrate your body. MicrobiomeX® has been shown to decrease fecal calprotectin, indicating it lowers gut inflammation and thus, your gut health benefits from this product.
Moreover, MicrobiomeX® was shown to be able to lower NF-κB levels in a co-culture study with Caco-2 cells line and macrophages. NF-κB is a proinflammatory transcription factor involved in the production of inflammatory chemokine such as TNF-a, which accordingly was shown decreased in the same study.
The bottom line
There are several ways your gut helps to fight against pathogens that cause disease. It is good to boost your immune system and the citrus flavonoids in MicrobiomeX® offer a way to support your immune system naturally.
The Link between Gut and Brain Health
The Link between Gut and Brain Health
The bidirectional communication system between your gut and brain is called the gut-brain axis. These two organs are connected through the vagus nerve, neurotransmitters, production of short-chain fatty acids (SCFAs) by gut microbiota and the immune system. This gut-brain link works in both directions. Gut bacteria affect brain health and, therefore, altering your gut bacteria through compounds such as probiotics and prebiotics may improve your brain health.
The Gut-Brain Connection
Did you ever “go with the gut” to make a decision? Have you ever felt “butterflies in your stomach” when nervous? This is because the brain and the gastrointestinal system are closely connected.
The bidirectional communication system between your gut and brain is called the gut-brain axis. These two organs are connected both physically through the vagus nerve and biochemically through hormones and neurotransmitters.
Gut microbiota has an important impact on the gut-brain axis, interacting not only locally with intestinal cells and enteric nervous system (ENS), but also directly with the central nervous system (CNS).
The Vagus Nerve
Your gut contains 500 million neurons, connected to your brain through the nervous system [1].
One of the biggest nerves connecting your gut and brain is the vagus nerve, which sends signals both ways. Gut microbiota communication with the brain, therefore, involves the vagus nerve [2].
Conditions such as Chron’s disease and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where the vagus nerve is an important component.
People suffering from these conditions actually have a reduced vagal tone, which indicates a decreased function of the vagus nerve [3].
Neurotransmitters
Your gut and brain are also connected through neurotransmitters. Neurotransmitters produced in the brain have an impact on our feelings and emotions.
Many of these neurotransmitters are produced by our gut cells and microbiota as well.
Around 90% of serotonin, a neurotransmitter that contributes to feelings of happiness, is produced by enterochromaffin cells, a group of gut mucosal cells [4].
Gamma-aminobutyric acid (GABA), a neurotransmitter that helps control feelings of fear and anxiety, is also produced by many species of Lactobacillus and Bifidobacterium in the gut microbiota [5].
Production of SCFAs by gut microbiota
Gut microbiota produces short-chain fatty acids (SCFAs), such as butyrate, propionate and acetate.
These SCFAs have a lot of health benefits in the gut, including maintaining the intestinal barrier, increasing mucus production and reducing gut inflammation. On top of that, they also play a role in the gut-brain interaction.
SCFAs can affect brain function in different ways. They are able to stimulate the sympathetic nervous system, mucosal serotonin release and influence the memory and learning process in the brain [6].
Immune system
Your gut and brain are also linked through the immune system. The microbiota provides essential signals for the development and function of the immune system.
The microbiota, its metabolites and components are not only necessary for immune homeostasis, but they also influence your susceptibility to many immune-mediated diseases and disorders [7].
If the gut barrier becomes leaky, bacteria and lipopolysaccharide (LPS) –an inflammatory toxin produced by some bacteria– can enter the blood, causing inflammation.
Inflammation and high LPS content in the blood are associated with brain disorders, such as depression and dementia [8].
The Role of Probiotics and Prebiotics in the Link between Gut and Brain
The gut-brain connection works in both directions. Gut bacteria affect brain health and, therefore, altering your gut bacteria may improve or worsen your brain health.
Probiotics are beneficial live bacteria. Psychobiotics are a class of probiotics that are able to produce and deliver neuroactive substances such as GABA and serotonin, which act on the brain-gut axis [9].
Studies have found that some psychobiotics have antidepressant or anxiolytic activity. These effects may be mediated via the vagus nerve, spinal cord, or neuroendocrine systems [10].
Prebiotics are compounds derived from non-digestible carbohydrates, mostly fibre. Prebiotics may also affect brain health by lowering cortisol levels, the stress hormone [11].
Beneficial Foods for the Gut-Brain Axis
Some foods can be beneficial for the gut-brain axis. These include the following:
• Probiotic foods. Probiotics can be found in fermented foods and drinks, such as yoghurt, kefir, tempeh or kombucha.
• Prebiotic foods. Prebiotics can be found in high fibre foods, such as vegetables, fruits, nuts, seeds and whole-grain products.
• Omega-3 fats. Omega-3 fatty acids can improve microbiota diversity [12]. These fats can be found in fatty fish, such as salmon, mackerel, tuna, herring and sardines.
• Polyphenol-rich foods. Polyphenols are found in foods such as cocoa, citrus, green tea, olive leaf and coffee. These compounds, digested by gut bacteria, increase healthy bacteria strains and may improve cognition [13].
• Tryptophan-rich foods. The amino acid tryptophan is the precursor of serotonin. Tryptophan is found in milk, cheese, oats, turkey and chicken, among others.
Curious to know more about brain health?
Did this article spark your interest in brain health and how you can improve it? Here you can find out everything you need to know about brain health and what ingredients are best to keep a healthy brain!
