Everything you need to know about Prebiotics and the gut microbiome

Gut talk with Dr Raylene Reimer

– Gut Talk with Dr. Raylene Reimer –

Dr. Raylene Reimer is a professor of nutrition in the Faculty of Kinesiology and Cumming School of Medicine at the University of Calgary.
Learn more about what she has to say about the importance of extablishing a healthy trajectory from early life to adulthood. Dr. Reimer has an internationally recognized translational research program focused on the role of diet in modifying gut microbiota and host metabolism in the context of obesity, diabetes, and other chronic diseases such as fatty liver disease and osteoarthritis. She has done extensive research in animal models to study how maternal diet influences offspring’s gut microbiota, insulin resistance, and obesity risk. Translating findings from animal models to human clinical trials is a key way in which Dr. Reimer spans bench to bedside research. She served on the international expert panels that defined the scope and appropriate use of the terms prebiotics and synbiotics. She is also a Registered Dietitian and a Full Scientist in the Alberta Children’s Hospital Research Institute.

Prebiotics and Gut Microbiota: Establishing a Healthy Trajectory from Early Life to Adulthood

You’ve mentioned before your motto in life is “Happy Gut, Happy Life”- why is that?

My research career began 30 years ago during my PhD when I studied the effects of a blend of different dietary fibers on diabetes outcomes. When I started working as a professor at the University of Calgary, my interest in fiber led me to a unique type of fiber called prebiotic fiber. At the time, it was well known that prebiotic fiber could increase levels of the beneficial bacteria Bifidobacterium in the gut but the full scale health implications of this weren’t well known. Shortly after I started working with prebiotic fiber, the gut microbiome was first described by a group of researchers in the United States as an important regulator of body weight and fat mass. Soon after, many other researchers around the world began to investigate the gut microbiota and its links to a variety of diseases and as they say, the rest is history! As someone who had spent their entire research career studying dietary fiber, it is especially encouraging to know that one of the best foods for a healthy gut microbiome is dietary fiber. Fiber and particularly prebiotic fiber have the potential to impact multiple different conditions and promote a healthy microbiome. Defining exacting what this healthy microbiome looks like has been difficult and researchers have not been able to identify a single ‘healthy’ microbiome composition. What we do know is that the gut microbiome performs a number of important functions that promote our health as humans. These include things like helping us harvest energy from fiber, training our immune system, producing certain vitamins, enhancing our intestinal barrier, and suppressing the growth of pathogens. The more researchers learn about the gut microbiome and its vital role in promoting health, the more it appears that ensuring your gut is healthy will help keep the rest of you healthy.

What are some practical ways in which a person can take care of their gut microbiome?

Researchers are continuously discovering more about the factors that promote a healthy gut microbiome. In infancy, we know that being born vaginally, being breastfed, and not being exposed to antibiotics all help to establish the foundations of a healthy microbiome. As we get older, diet is one of the most important influences on our gut microbiome. A diet rich in a variety of dietary fibers and other gut-microbiome friendly foods and ingredients (prebiotics, probiotics, fermented foods, etc.) is one of the most important things you can do to promote a diverse and well-functioning gut microbiome.  Beyond that, limiting your intake of fatty and sugary foods, highly processed foods, and those low in fiber is beneficial.

There is so much confusion out there on all the ‘biotics’ terms. The term ‘prebiotic’ is being used to describe many ingredients and products.

As Health Care professionals, how can we make sure we use the term “prebiotic” correctly? What about inulin,  is it a proven prebiotic?

The definition of a prebiotic is very specific and has been clearly defined by organizations such as the International Scientific Association for Probiotics and Prebiotics (ISAPP). The definition was updated in 2017 and is “a substrate that is selectively utilized by host microorganisms conferring a health benefit“ (DOI: 10.1038/nrgastro.2017.75). The key criteria in this definition are that prebiotics need to be selectively utilized and have adequate evidence of health benefit for the host, meaning that not all fibers or ingredients will meet the definition of a prebiotic. Some fibers have the potential to be prebiotics and are therefore called candidate prebiotics (e.g. pectin, resistant starch, soybean oligosaccharides). Research on these and other compounds with the potential to be prebiotics is ongoing and will ultimately determine if they meet the definition. In the meantime, the proven or confirmed prebiotics are inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS). As Health Care professionals it is important to use the term prebiotic appropriately to avoid confusion for patients and consumers. For example, products or supplements containing inulin are accurately called prebiotic whereas other fibers that are not confirmed prebiotics can still be a very important part of a healthy diet, but we should call them fiber until they are proven to be prebiotic.

You talk in your research about how certain bacteria present in early life in the gut microbiota can prevent disease.

Can you explain this concept a bit more and what we can do about it practically?

It is well known now that the first 1000 days of a child’s life represent a critical window when the immune system matures and the gut microbiota is established. The importance of early life factors for lifelong health or susceptibility to disease is further emphasized by the developmental origins of health and disease concept where exposures during pregnancy and infancy can ‘program’ an individual’s risk for chronic disease later in life. The gut microbiota plays a major role in this programming. Some of the most well-studied factors that influence the development of a child’s gut microbiome include mode of delivery (vaginal versus C-section), antibiotic exposure (mother and/or infant), feeding method (breastfeeding versus formula feeding), gestational age (term versus premature), and maternal health (obesity, gestational diabetes). Of these, breastfeeding is one of the most crucial factors. Along with important nutrients and immune factors, breast milk contains human milk oligosaccharides (HMOs) which are candidate prebiotics. HMOs promote the growth of an important bacteria in the infant gut called Bifidobacterium. As the most abundant bacteria in the gut of healthy breastfed infants, Bifidobacterium are critical in promoting immune system development, helping to suppress pathogenic bacteria in the gut, and producing short chain fatty acids that enhance the intestinal barrier and affect metabolism. Confirmed prebiotics such as inulin, FOS, and GOS are also excellent promoters of Bifidobacterium in the gut and some are added to infant formulas.

What do we know about prebiotics and their ability to affect behavior? What else is emerging in research in the field of the gut microbiome and prebiotics?

The microbiome – gut – brain axis is a fascinating emerging field of research. The gut microbiome has been implicated in several brain-related diseases and conditions including depression and anxiety, degenerative disorders such as Parkinson’s disease, Alzheimer’s disease, and neurocognitive development. The identification of altered microbiota signatures in these conditions has as a consequence generated a lot of interest in using diet (e.g. Mediterranean diet, fermented foods) and ‘biotics’ (e.g. probiotics, prebiotics, postbiotics) to restore the microbiome and improve brain health and behavior. Much of the research in this area has been conducted in animals but there are a growing number of translational studies in humans. For example, prebiotics have been shown to reduce anxiety scores in patients with irritable bowel syndrome and to decrease the stress response. Future well-designed clinical trials with larger populations are needed to capitalize on the full potential of prebiotics (as well as probiotics and synbiotics) to modulate the gut – brain axis. Numerous other emerging applications for prebiotics to improve health are also on the horizon. Clinical trials are currently underway to test the effects of prebiotics for preterm infants, epilepsy, sleep and immune function, acute stress, and several other interesting areas. Health professionals can look forward to seeing the outcomes of these studies in the future.

Your research has targeted the gut microbiome with prebiotics in adults and children with obesity.

How can prebiotics help in this situation?

Although obesity is a multifactorial disease, it is now recognized that the gut microbiome plays an important role in regulating body weight and adiposity. Individuals with obesity have an altered gut microbiome that in many cases is in low in Bifidobacterium. Changes in the intestinal barrier that lead to increased intestinal permeability have also been seen in the development of obesity and insulin resistance. Knowing the ‘bifidogenic’ effect of prebiotic fibers and based on the evidence from animal studies that they can improve the intestinal barrier, we were interested in testing the effects of prebiotics in adults and children with overweight or obesity. In the adult study, oligofructose was shown to reduce body weight and body fat more so than the placebo. In the child study, oligofructose-enriched inulin was shown to reduce body fat and improve appetite control compared to the placebo. Although not all studies with prebiotics show significant changes in body weight, a recent meta-analysis of clinical trials with isolated soluble dietary fiber supplementation (many of which were inulin or FOS studies) showed significantly higher reduction in body weight with at least 12 weeks of supplementation in patients with overweight or obesity (DOI: 10.3390/nu14132627) suggesting that how long the supplements are taken is likely important.

You have done some research showing that prebiotics work on the knee joint. How is this possible?

This is an interesting and emerging field of study that takes advantage of the gut-joint axis or in other words the communication that takes place between the gut microbiota and various joints in the body. The communication between these two sites may occur via metabolites that the gut microbiota produce (e.g. short chain fatty acids) that in turn alter inflammation. Based on research we conducted in an animal model showing the protective effects of oligofructose on knee joint health, we were interested in testing whether prebiotic supplementation could similarly improve the function of the knee joint in humans that had knee osteoarthritis and obesity. We observed some promising results in terms of better physical performance in the participants and reduced fat in the trunk region. Additional studies will be needed to confirm if prebiotics can be used as a treatment that reduces pain and improves function in those suffering from osteoarthritis.

Inulin is sometimes added to foods, is this as good as eating foods naturally rich in inulin?

Inulin is naturally occurring in a number of foods including onions, garlic, Jerusalem artichokes, beets, melons, nectarines, and wheat. One of the richest sources of inulin is the chicory root from which inulin can be extracted and used as a supplement or added to foods as an ingredient. For everyday health, it is important to include prebiotic-rich foods in one’s diet. Research shows that as little as 3 g/day of chicory-derived inulin is sufficient for a shift in the microbiota (i.e. increase in beneficial Bifidobacterium) and improved digestive health.  For certain populations or health conditions, however, they may benefit from a higher amount of prebiotic than they could easily manage to consume from just foods. In these cases, research studies have tested doses of prebiotics that range from 3-21 grams per day with many studies using 15 grams per day, depending on the condition that is being examined (DOI: 10.1080/10408398.2022.2098246). Supplementation or the addition of prebiotics to common foods (e.g. snack bars) may also be a way that we can fill the “dietary fiber gap” that exists because very few adults and children consume sufficient fiber.

If we aim to target health benefits through feeding our gut microbiome, shouldn’t it be sufficient to just eat fermented foods? Do we need to add prebiotics to our diet?

Fermented foods have been defined by the International Scientific Association for Probiotics and Prebiotics (ISAPP) as “foods made through desired microbial growth and enzymatic conversions of food components” (DOI: 10.1038/s41575-020-00390-5). Fermented foods have a long history of use by humans and can be classified as those that have live microorganisms present and those that do not. Live microorganisms are generally present in foods and beverages such as yogurt, kefir, tempeh, non-heated fermented vegetables including sauerkraut and kimchi, and kombuchas. Some fermented foods no longer contain live microorganisms at the point of consumption because they are killed after fermentation (e.g. baking of bread, heat-treating or pasteurizing fermented vegetables, soy sauce, and some kombuchas). While historically used for food preservation, fermentation can also improve the nutritional value and the taste and texture of foods and for this reason has been used by cultures around the world to create many staple foods. Feeding a healthy gut microbiome ideally includes the consumption of a variety of microbiome-supporting whole foods and ingredients meaning that fermented foods, prebiotics, and probiotics all have a role to play in this common goal. And interestingly, some fermented foods also contain prebiotics. For example, fermented grains or vegetables could contain oligosaccharides thereby providing a prebiotic and a fermented food. One distinction between fermented foods and prebiotics is that a proven prebiotic must confer a health benefit for the consumer whereas there is no requirement in the definition of fermented foods that they must confer a health benefit. Aside from a substantial number of human clinical studies with yogurt and cultured dairy products, there are currently few randomized controlled trials that have investigated the benefits of other fermented food products for human health. Prebiotics on the other hand have a strong body of evidence for their health benefits. Overall, one should strive for a daily diet that includes many gut microbiome friendly foods and ingredients.

What about people with IBS or those who follow FODMAP protocols, what should they do if they want the benefits of a prebiotic for their gut barrier function?

A low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet is one that is low in small-chain carbohydrates that are poorly absorbed in the small intestine. In some individuals (e.g. those with irritable bowel syndrome (IBS)), foods containing FODMAPs can lead to gas and bloating. Eating a low FODMAP diet can reduce symptoms, but research has shown that this diet can limit fiber and calcium intake and also reduce a number of beneficial bacteria in the gut including Bifidobacterium and Faecalibacterium. To overcome this, scientists have begun to test whether certain prebiotics might help reduce symptoms while maintaining the abundance of healthy bacteria like Bifidobacterium. In these studies, supplementing a low FODMAP diet with GOS was shown to provide greater symptom relief for patients with IBS compared to control (DOI: 10.1111/apt.17609; DOI: 10.14309/ajg.0000000000000641). Other studies in this area have shown that increased sensitivity to fructose and lactose may account for a good deal of the variance in symptom severity in IBS and that inulin increases Bifidobacterium while still being well tolerated in patients with a history of abdominal discomfort. For patients with IBS, prebiotics might be an alternative or additive to a low FODMAP diet; ongoing research will hopefully tell us which dose and prebiotic might do this best.