What is the gut microbiota?

The gut microbiota refers to the complex microbial ecosystem harboring the human gastrointestinal tract. It is estimated that ~10¹³ microorganisms―bacteria, archaea, and eukarya and other microorganisms may be present in the gut. Studies have shown that the gut microbiota has a significant impact on human health and disease (Derovs et al., 2019; Mills et al., 2019; Valdes et al., 2018).

Ninety percent of the gut microbiota is represented by two phyla―Firmicutes and Bacteroidetes. The Firmicutes phylum is comprised of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus, with Clostridium genera representing 95% of the phyla. Bacteroides and Prevotella are the predominant genera in the Bacteroidetes phylum in the gut (Rinninella et al., 2019). The ratio of Firmicutes to Bacteroidetes is believed to impact host health, for example, a higher ratio is observed in individuals who are obese and a lower ratio in lean individuals (Senella, 2016). Other phyla include Actinobacteria, Proteobacteria, Fusobacteria. The Actinobacteria phylum is less abundant relative to other phyla and primarily represented by the Bifidobacterium genus (Rinninella et al., 2019).

What is the microbiome?

There are a couple of definitions of microbiome. One definition which includes the habitat/environment of the microorganism, defines microbiome as the “entire habitat, including the microorganisms (bacteria, archaea, lower and higher eurkaryotes, and viruses), their genomes (i.e., genes), and the surrounding environmental conditions” (Marchesi & Ravel, 2015). Another definition only includes the genetic material and defines microbiome as the collective genetic material of the microorganisms found in a particular environment, for example, the human gut microbiome is the collection of microorganisms’ genomes residing in the human gut. The human genome consists of about 23,000 genes, whereas gut microbiota encodes over three million genes regulating the production of thousands of metabolites, influencing the host’s fitness, phenotype, and health (Marchesi & Ravel, 2015; Valdes et al., 2018).

What is microbial diversity?

Microbial diversity is a measure of how many different species are evenly distributed within the microbial community. Low microbial diversity relative to the ‘healthy’ gut microbiota could be an indicator of dysbiosis (Valdes et al., 2018).

What is dysbiosis of the gut?

There are a wide variety of bacteria in the gut, while some may promote health, others may lead to disease states or adverse health condition(s), and some are neutral in their interactions with their host. Many bacteria can shift between being health promoting, detrimental, or neutral depending on factors, such as diet and over health of the host. Dysbiosis refers to imbalances in gut microbiota communities. It is a shift of the gut microbiota to an imbalanced, less healthy state―a decrease in health promoting bacteria and/or an increase in disease promoting bacteria. Low microbial diversity relative to the ‘healthy’ gut microbiota could be an indicator of dysbiosis. Although our understanding of the role of gut microbiota is evolving, an association has been observed between gut microbiota dysbiosis and disorders, such as irritable bowel syndrome, inflammatory bowel disease, celiac disease, obesity, and type 2 diabetes (Mills et al., 2019; Rinninella et al., 2019; Valdes et al., 2018).

Can the gut microbiota have detrimental impacts?

Some gut microbiota may produce harmful toxins. For example, some protein fermentation products, such as ammonia, p-cresol, phenols, and hydrogen sulfide can be toxic. For example, p-cresol can damage the liver and kidney. Lipopolysaccharides and other lipids produced by bacteria can cause inflammation (Conlon & Bird, 2015).

Why is the gut microbiota important?

The gut microbiota encodes over three million genes compared with 23,000 human genes and regulates  the production of thousands of metabolites, influencing the host’s fitness, phenotype, and health (Valdes et al., 2018). The gut microbiota serves many functions and is integral to the health of the host, as detailed below.

Production of nutrients and bioactive components
Diet that is typically comprised of a variety of fruits, vegetables, and cereals, provide essential carbohydrates and dietary fibers. Dietary fibers, consisting mostly of plant cell wall polysaccharides and resistant starch (resistant starch is the total amount of starch and the products of starch degradation that are not digested in the small intestine (Zaman & Sarbini, 2016), are not digested or absorbed in the small intestine; thus, they enter the large intestine where they are fermented by the gut microbiota. The gut microbiota also uses carbohydrates from other sources, such as carbohydrates derived from meat and poultry sources and glycome from the host epithelial cell/tissue, as sources of energy. The major end products of microbial carbohydrate fermentation in the colon are short-chain fatty acids (SCFAs), including butyrate, propionate, and acetate. SCFAs are rapidly absorbed by the intestinal epithelial cells, where they are involved in a number of cellular and regulatory processes described below. Only 5% of SCFAs are excreted in feces (Mills et al., 2019).

Butyrate is a major fermentation product of a number of Firmicutes bacteria. It is the preferred energy source for intestinal epithelial cells and is important in the development of the intestinal barrier, the layer that acts as a barrier between the body and intestinal lumen material. Butyrate is also important in brain function, and is shown to exhibit anti-cancer and anti-inflammatory properties (Mills et al., 2019).

Propionate is a major fermentation product of many Bacteroidetes species. It activates the synthesis of glucose in the liver and intestine and has been shown to reduce proliferation of cancer cells in the liver (Mills et al., 2019).

Acetate, another SCFA produced in the gut by most anaerobic microorganisms plays a role in regulating immune response. Acetate is shown to promote intestinal antibody IgA responses to the gut microbiota (Mills et al., 2019), which protects the mucosa.

SCFAs also stimulate secretion of gut hormones, such as glucagon-like peptide 1 (GLP-1) and plasma peptide YY (PYY), which play a role in energy regulation by controlling appetite and satiety. Changes in the production of these compounds due to disturbances to the gut microbiota could result in pathological consequences for the host. For example, increased acetate production arising from alterations in the gut microbiota was shown to promote metabolic syndrome (a group of risk factors that raises risk for heart disease and other health conditions, such as stroke and type 2 diabetes (National Heart, Lung, and Blood Institute/National Institutes of Health., n.d.) in rodents (Mills et al., 2019).

Several essential vitamins, including B vitamins, such as thiamin (B1), riboflavin (B2), nicotinic acid (B3), pantothenic acid (B5), pyridoxine (B6) biotin (B7), folic acid (B9), cobalamin (B12), as well as vitamin K can be synthesized by the gut microbiota (Mills et al., 2019).

The gut microbiota metabolizes primary bile acids to secondary bile acids in the colon. In animal models, secondary bile acids have been shown to regulate weight gain, lipid metabolism, and cholesterol levels via regulation of key genes in the liver or small intestine (Mills et al., 2019).

Enzymes produced by microorganisms in the gut influence digestion and health. For example, enzymes that breakdown undigested carbohydrates (such as complex polysaccharides) or phytase that can help increase the availability of minerals (such as calcium, magnesium, and phosphate) for the host, by releasing the minerals that are bound to phytic acid in grains (Conlon & Bird, 2015).

The gut microbiota also produces neurochemicals that may influence the peripheral enteric and central nervous systems. For example, certain strains of bacteria in the human gut were shown to produce gamma amino butyric acid (GABA), a major inhibitory (blocks or inhibits certain signals in the brain) neurotransmitter in the brain. Neuropsychiatric disorders, including anxiety and depression have been linked to the dysfunction of the GABA system. In the human gut, spore forming bacteria could synthesize serotonin, another neurotransmitter. Serotonin plays an important role in the regulation of mood. Although serotonin produced by the gut microbiota is unable to cross the blood-brain barrier under normal physiological conditions, it is an important signaling molecule and is involved in peristalsis, vasodilation, pain perception, and nausea, as well as in neuron development and maintenance of the enteric nervous system (Mills et al., 2019).

Protection against pathogens
The gut microbiota protects the host against colonization by exogenous pathogens and overgrowth of potentially pathogenic endogenous microbes. Overgrowth and colonization is prevented directly by competition among the microorganisms for nutrients and colonization sites and through the production of antimicrobial substances, such as bacteriocins, and indirectly by modulating the host cellular surfaces and the host immune system (Mills et al., 2019).

Host immunity and mucosal layer integrity
Animal and in vitro studies have shown that the gut microbiota promotes immune system maturation and host homeostasis, for example, through production of IgA and metabolites (e.g., SCFAs), which are important signaling molecules for the immune system. The gut microbiota influences the density and composition of the gastrointestinal mucosal layer, which acts as a protective barrier for the epithelial cells making it difficult for pathogens to reach them, for example (Mills et al., 2019).

Variation in the gut microbiota within an individual (intra-individual)

In each individual, the gut microbiota varies depending upon the region of the gastrointestinal tract. Further, an individual’s microbiota undergoes change due to infant transitions, age, diet, and environmental factors, such as antibiotic use. However, for each individual, a healthy host–microorganism balance is needed for optimal metabolic and immune function, primarily for the prevention of disease conditions (Rinninella et al., 2019). These variation-inducing factors are addressed in further detail below.

Gastrointestinal region

Within the gut, the microbiota composition varies depending on the anatomical region, where within each region of the gut the microbiota is influenced by such factors as, physiology, pH and oxygen tension, substrate availability, and digesta flow rate. For example, the small intestine provides a more challenging environment for the gut microbiota due to the presence of bile, whereas, the large intestine harbors a much larger microbial community, due to neutral or mildly acidic pH (Rinninella et al., 2019).

Infant transitions

Gestational age at birth (preterm vs. full term), type of delivery (vaginal vs. C-section), method of feeding (breast milk vs. infant formula), and weaning period (introduction of solid foods and the termination of milk-feeding/weaning) impact the diversity and composition of an infant’s gut microbiota. For example, preterm infants show low diversity with an increased colonization of potentially pathogenic bacteria. Infants fed breastmilk have a more complex and diverse beneficial microbiota composition compared with formula-fed infants, for example (Rinninella et al., 2019).

Age

After birth, microbiota composition and diversity increase with age and trends towards an adult-like composition, which is established between the ages of 2-5 years. The microbiota composition is dominated by three bacterial phyla (Firmicutes, Bacteroidetes, and Actinobacteria), influenced by genetics, environment, diet, lifestyle, and gut physiology. In healthy adults, the gut microbiota is primarily composed of Firmicutes and Bacteroidetes. In older adults (age 70 years and above), gut microbiota composition can be affected by changes in digestion and absorption of nutrients, weakness in immune activity, and changes in dietary habits (Mills et al., 2019; Rinninella et al., 2019). Ageing leads to significant compositional and functional changes in elderly gut microbiota, characterized by a decline in microbial diversity, an increase in the abundance of opportunistic pathogens, and a decrease in species associated with the production of SCFAs, that benefit the host. For example, butyrate, a SCFA serves as a source of energy for the intestinal cells, for example (Mills et al., 2019).

Do vitamins and minerals in the diet impact the gut microbiota?

Vitamins are essential for supporting normal physiological functions. Diet is the primary source of most vitamins, as they cannot be synthesized by humans. However, some vitamins, such as vitamin K and some B vitamins, including biotin, cobalamin, folate, nicotinic acid, pantothenic acid, pyridoxine, riboflavin, and thiamine are synthesized by gut microbiota. Vitamins and gut microbiota may interact, where dietary vitamins and/or vitamins produced by the gut microbiota are responsible for modulating beneficial/detrimental species based on their concentration within the microenvironment. Studies in animals and humans have shown that vitamin A can modulate health‐beneficial microbes, such as Bifidobacterium, Lactobacillus, and Akkermansia. Some B vitamins have been shown to promote bacterial colonization, modulate bacterial virulence, and modify host defense. For example, preliminary studies in animals show that niacin and pyridoxine could lead to an abundance of deleterious/potentially pathogenic species in the gut. Vitamin C supplementation could modulate health‐beneficial microbiota, such as Bifidobacterium and Lactobacillus. Vitamin D and E are independently shown to modulate health‐beneficial microbes, such as Roseburia and may also reduce Firmicutes-to-Bacteroidetes ratio. Studies in animals and humans show that vitamin supplementation could modulate the gut microbiota, however, the effect is dependent on the vitamin level in the host, hence further research is needed to determine any adverse reaction by excessive supplementation of vitamins (Mills et al., 2019; Yang et al., 2020).

There is limited evidence on the role of minerals and trace elements in modulating the gut microbiota. Studies reporting the effects of minerals and trace elements on gut microbiota have evaluated changes following supplementation with minerals and trace elements to address micronutrient deficiency. For example, studies in animals report that calcium supplementation modulates Akkermansia and Bifidobcterium. Studies in animals and humans report decreased abundance of beneficial microbes and increased abundance of detrimental microbes with iron supplementation, however, evidence on the effects of iron supplementation on gut microbiota is inconclusive. Limited research suggests that phosphorus supplementation increases SCFAs, however more studies are needed to determine the impact of phosphorus on gut microbiota. The effects of zinc and selenium supplementation, independently, on the human gut microbiota is lacking. However, animal studies report that zinc and selenium supplementation, independently, increase beneficial microbes and reduce detrimental microbes. Iodine supplementation in animals induced gut dysbiosis and also reduced the abundance of beneficial microbes (Yang et al., 2020).

Are there other food components that could impact the gut microbiota?

Prebiotics

The definition of a  prebiotic has been revised several times since it was first introduced in 1995. A prebiotic is defined as “a substrate that is selectively utilized by host microorganisms conferring a health benefit.” Previously, prebiotics consisted of non-digestible carbohydrates, but now the concept has been expanded to include other food components (Danneskiold-Samsøe et al., 2019; Gibson et al., 2017). Although non-digestible carbohydrates that may have a prebiotic effect are found in cereals, as well as onions, garlic, bananas, chicory root, and Jerusalem artichokes, they are typically present at low levels and may not exert the desired prebiotic effect. Inulin, FOSs, GOSs, xylooligosaccharides, arabinoxylan oligosaccahries, and resistant starch have been shown to increase the abundance of some beneficial bacterial species, such as Bifidobacterium, Lactobacillus, Ruminococcus bromii, and Fecalibacterium. Microbial fermentation of prebiotics results in metabolites such as SCFAs, hydrogen, and carbon dioxide. Evidence on health effects of prebiotics is evolving, however, prebiotics, such as GOS and FOS have been associated with improving digestion, reducing constipation, and resisting infection. Although dietary fiber and prebiotic consumption can modulate the gastrointestinal microbiota, individual responses can vary depending on the host genetics, host microbial composition, and the type and amount of dietary fiber or prebiotic consumed. Further, the changes only last as long as the prebiotic(s) is consumed (Conlon & Bird, 2015; Danneskiold-Samsøe et al., 2019; Holscher, 2017; Valdes et al., 2018).

Probiotics

Probiotics are live microorganisms that when administered in adequate amounts confer a health benefit to the host (Conlon & Bird, 2015). Probiotics are added to some foods, beverages, and dietary supplements. The microorganisms most often used are Lactobacillusand Bifidobacterium, but others, such as Saccharomyces, Streptococcus, Enterococcus, Escherichia, and Bacillus are also used. Fermented foods, such as cultured milk and yogurt, containing lactic acid bacteria are known sources of probiotics that may have a beneficial effect on the gut and human health. Probiotics may increase the abundance of beneficial microbiota and/or decrease the abundance of detrimental microbiota. Most research on the potential health benefits of probiotics have focused on health conditions, such as acute infectious diarrhea, antibiotic-associated diarrhea, ulcerative colitis, irritable bowel syndrome, hypercholesterolemia, and obesity. Health benefits associated with probiotics are dependent on the specific strain(s) and dosage, as well as the number of live cells at the time of consumption. Since probiotics do not necessarily colonize the gastrointestinal tract, they may need to be consumed regularly (Hill et al., 2014; Hills et al., 2019; Mermelstein, 2019; Singh et al., 2017; Valdes et al., 2018).

In food and beverage products, the specific strains used are dependent, in part, on the tolerance of the bacteria to various conditions. For example, Lactobacillus and Bifidobacterium cannot withstand high temperature, therefore they are commonly used in refrigerated or frozen products (primarily yogurt) and in shelf-stable food products, such as dry cereals if very dry, low-water activity conditions are maintained. Spore-forming microorganisms such as Bacillus can survive heat processing and may be used in a variety of processed food products (Mermelstein, 2019).

Polyphenols and phytochemicals

Polyphenols are phytochemicals found in many  fruits, vegetables, grains, and tea. Polyphenols are associated with disease prevention (e.g., cardiovascular disease) through antioxidant, anti-inflammatory, cancer preventive, and neuroprotective properties. Studies show that microbiota are capable of metabolizing phenolic compounds, increasing both bioavailability and biological activity. In vitro studies, studies in animals, and limited clinical trials suggest that supplementation of phenolic compounds could modulate the gut microbiota by increasing the abundance of beneficial microbiota (e.g., Bifidobacterium, Lactobacillus, Akkermansia, and Fecalibacterium sp) and/or modulating Firmicutes-to-Bacteroidetes ratio (Conlon & Bird, 2015; Danneskiold-Samsøe et al., 2019; Yang et al., 2020).

Use of antibiotics

Antibiotic treatment can modify the composition of gut microbiota. Broad-spectrum antibiotics can cause an imbalance between Firmicutes and Bacteroidetes, decreasing both the diversity and abundance during the treatment period. The changes in microbial composition depend on the type of antibiotic administered, dose, length of exposure, pharmacological action, and the target bacteria (Rinninella et al., 2019).

Does my diet impact the gut microbiota?

Diet is considered to be one of the most important modifiers of the gut microbiota and could lead to relatively large shifts on a daily basis. These changes, while rapid, tend to be only on a short-term basis (Danneskiold-Samsøe et al., 2019; David et al., 2014; Yang et al., 2020). Macronutrients (carbohydrates, proteins, and fats), micronutrients (vitamins and minerals), prebiotics, probiotics, food additives, and other components can modulate the gut microbiota. Due to the complex compositional nature of the diet, it is difficult to clearly define/determine the role of individual dietary components on gut microbiota composition and diversity. The diversity found within the human gut microbiota is greater than within our own cells, further adding to the complexity in understanding the effects of microorganisms and their metabolites on disease conditions and human health. The following information on the role of diet on gut microbiota should be regarded in this complex context. The diet can impact the number and diversity of the gut microbiota. Studies have identified some groups of gut microbes, such as from the genera Bifidobacterium, Lactobacillus, Akkermansia, Fecalibacterium, Eubacterium, Roseburia, and Ruminococcus to be associated with good health outcome(s). While other studies have reported that the abundance of certain bacteria, such as some species from the genera Clostridium, Enterobacter, Enterococcus, Bacteoidetes, and Ruminococcus that could potentially contribute to the development or progression of major non-communicable diseases (Danneskiold-Samsøe et al., 2019; Yang et al., 2020).

Dietary patterns and diets

The macronutrient and micronutrient content of plant-based and Western-type dietary patterns are shown to be associated with chronic disease risk factors. Consumption of a plant-based versus Western-type diet could have a distinct impact on gut microbial communities, resulting in metabolites that may influence processes potentially linked to chronic disease pathology (Sheflin et al., 2017). Individuals consuming plant-based diets (high in fiber, low in lipids and proteins) have exhibited greater bacterial diversity and richness compared with those who consume animal-based diets (high in lipids, proteins, and low in fiber). In an intervention study, plant-based diets increased the abundance of fiber fermenting bacteria, such as Roseburia, whereas animal-based diets increased the abundance of microorganisms which thrive in the presence of bile, including Bacteroides. Ruminococcus, another enterotype found in human gut is associated with long term fruit and vegetable consumption and is influenced by both plant- and animal-based diets. Ruminococci may produce butyrate, primarily by degrading complex carbohydrates, such as cellulose and resistant starch, found in plant-based foods (Pallister & Spector, 2016; Sheflin et al., 2017; Tomova et al., 2019).

A summary of the effects of specific dietary components on gut microbiota is provided below. Although in vitro, animal, and clinical studies report on the effects of specific macro- and micro- nutrients on modulation of gut microbiota, there is a lack of data on how these specific nutrient components alter the gut microbiota in humans. Well‐defined, carefully controlled dietary interventions on various cohorts are needed to better understand the intra‐ and inter‐individual variability in how individuals and their microbiomes respond differently to dietary patterns and specific food components (Yang et al., 2020).

Does protein consumption impact the gut microbiota?

In a regular Western diet, dietary proteins (about 10-12%) that are not digested in the small intestine reach the large intestine, increasing proportionally with overall protein consumption. Dietary protein is a major source of nitrogen for gut microbiota and is essential for the production of beneficial metabolites such as SCFAs. Hence a combination of carbohydrates and protein in the gut can contribute to gut health. However, unlike carbohydrate fermentation, protein fermentation by gut microbiota produces a greater diversity of metabolites (such as, hydrogen sulfide, ammonia, aromatic compounds, SCFAs, branched chain fatty acids, other organic acids, ethanol, gases, and compounds with potential neuroactive activity (serotonin, GABA, histamine, etc.)), some of which may be essential to host health maintenance, while others may have detrimental effects (Conlon & Bird, 2015; Mills et al., 2019; Sanz et al., 2018).

Protein source or type has been shown to impact gut microbiota composition, due to differences in amino acid composition. Studies have shown variation in gut microbiota composition in animals fed different types of meat (pork, beef, chicken, and fish), milk, or plant proteins (e.g., soy, mungbean, and buckwheat) and suggests that plant-derived proteins promote beneficial microbiota with positive effects on host metabolism compared to proteins derived from animal sources (Mills et al., 2019; Yang et al., 2020).

Diet high in protein increase satiety, may favorably modify lipids, and potentially assist with weight management. However, they may have adverse effects on tissues and organs in the long-term and need further investigation (Conlon & Bird, 2015; Mills et al., 2019; Sanz et al., 2018). A recent review of the role of high-protein diets (25-30% of total energy intake) in weight management showed that high-protein diets generally decreased body weight and improved blood metabolic parameters along with modifying bacterial metabolites and co-metabolites found in feces and urine. Furthermore, the effects of high-protein diets on gut microbiota were heterogenous and dependent on the type of intervention, including protein type (plant or animal protein), though, further investigation is required (Blachier et al., 2019).

The effect of processing (e.g., thermal processing), which often impacts protein digestion and overall protein function, including modulation of the gut microbiome, is not fully understood and requires further investigation (Mills et al., 2019).

The impact of protein on gut microbiota composition and functionality is dependent on the source, quantity, and quality. These factors should be considered while investigating the effects of protein on gut microbiota (Mills et al., 2019; Yang et al., 2020).

Does fat and oil consumption impact the gut microbiota?

Some dietary fats escape absorption in the small intestine and reach the colon. Studies in animals and humans show that diets high in total fat (44-72 %) and saturated fat negatively impact the richness and diversity of the gut microbiota. This could be due to reduced access and quantities of other nutrients, such as carbohydrates and potential effects of lipids on secretion and composition of bile acids (Danneskiold-Samsøe et al., 2019; Mills et al., 2019; Sanz et al., 2018; Yang et al., 2020).

Studies in animals have shown variation in the composition and diversity of gut microbiota based on the type (e.g., lard vs. fish oil), profile (saturated fatty acids and mono- or polyunsaturated fatty acids (PUFAs)), and quantity of fat/lipids. Saturated fat has been shown to decrease health beneficial microbiota, such as Bifidobacterium and Fecalibacterium and increase Firmicutes-to-Bacteroidetes ratio. Unsaturated fat has been shown to increase the abundance of Akkermansia and Bifidobacterium and reduce Firmicutes-to-Bacteroidetes ratio. A recent review evaluating the impact of dietary fat on the gut microbiota and low-grade systemic inflammation concluded that saturated and high fat diets should be avoided, while encouraging intake of monounsaturated and omega-3 polyunsaturated fatty acids to regulate gut microbiota and inflammation towards promoting control of body weight/fat (Danneskiold-Samsøe et al., 2019; Mills et al., 2019; Sanz et al., 2018; Yang et al., 2020).

As previously noted, dietary fat consumption affects the secretion and composition of bile acids. The relationship between bile acids and gut microbiota is bidirectional. The gut microbiota is shown to regulate bile acid synthesis and modulate conjugation of secondary bile acids, whereas bile acids has been shown to modify the gut microbiota, by promoting the growth of some bacteria that use bile acids as a substrate or inhibiting (anti-microbial) other bacteria (Danneskiold-Samsøe et al., 2019; Sanz et al., 2018).

Does carbohydrate intake impact the gut microbiota?

Carbohydrates are the main source of energy for the host and the microbiota and have been shown to modulate beneficial microbes in both humans and animals. Simple carbohydrates (monosaccharides and disaccharides) are typically digested and absorbed in the small intestine. However, some carbohydrates may enter the large intestine undigested. Complex undigested carbohydrates, such as plant cell wall polysaccharides, resistant starch, non-starch polysaccharides, and oligosaccharides could serve as substrates for gut microbiota in the large intestine (Danneskiold-Samsøe et al., 2019; Mills et al., 2019; Yang et al., 2020).

The U.S. Food and Drug Administration (FDA) defines dietary fiber as “non-digestible soluble and insoluble carbohydrates (with 3 or more monomeric units), and lignin that are intrinsic and intact in plants; isolated or synthetic non-digestible carbohydrates (with 3 or more monomeric units) determined by the FDA to have physiological effects that are beneficial to human health.” Isolated or synthetic non-digestible carbohydrates, as approved by the FDA, as dietary fiber include: beta-glucan soluble fiber, psyllium husk, cellulose, guar gum, pectin, locust bean gum, and hydroxypropylmethylcellulose. Further, the FDA intends to propose that the following non-digestible carbohydrates be added to the definition of dietary fiber: mixed plant cell wall fibers (a broad category that includes fibers like sugar cane fiber and apple fiber, among many others), arabinoxylan, alginate, inulin and inulin-type fructans, high amylose starch (type-2 resistant starch), galactooligosaccharide, polydextrose, resistant maltodextrin/dextrin, cross linked phosphorylated starch (type-4 resistant star), and glucomannan, based on scientific review (U.S. Food and Drug Administration, 2020).

The physicochemical characteristics of fibers, such as fermentability, solubility, and viscosity determine their physiological effect(s) and/or fermentability by gut microbiota (Holscher, 2017). Dietary fibers can promote health benefits by mechanisms independent of gut microbial fermentation. For example, some dietary fibers have physiological effects, such as promoting bowel health by adsorbing water and increasing fecal mass and frequency of bowel movement. Fermentation can also increase the fecal mass through bacterial proliferation, though to a lesser extent (Conlon & Bird, 2015).

Not all non-digestible carbohydrates have the ability to modulate the gut microbiota, however those that are fermented by the gut microbiota result in metabolites, such as SCFAs, hydrogen, and carbon dioxide. Microbiota that are unable to ferment non-digestible carbohydrates, may use fermentation metabolites as substrates (Danneskiold-Samsøe et al., 2019; Mills et al., 2019; Yang et al., 2020).

In humans and animals, a diet high in fiber is shown to increase the abundance of Bifidobacterium and reduce the ratio of Firmicutes-to-Bacteroidetes. Studies have demonstrated that diets high in complex non-digestible carbohydrates, for example whole grain cereal, soluble corn fiber, barley kernel-based bread, and some non-digestible carbohydrates also known as prebiotics (e.g., arabinoxylans, arabinoxylan‐oligosaccharides, resistant starch, galactoologosaccharides (GOSs), and inulin type fructans) are shown to increase the abundance of one or more of the beneficial bacteria, such as Bifidobacterium sp., Lactobacillus sp., Akkermansia sp., Fecalibacterium sp., Roseburia sp., Bacteroides sp., Prevotella, Roseburia, Clostridium lepum, and Ruminococcus intestinalis. However, the extent of modulation of the gut microbiota depends on the amount and type of non-digestible carbohydrates consumed, age, length of intake/supplementation, and health condition (e.g., healthy, obese etc.) of the individual (Yang et al., 2020).

Galactooligosaccharides are added in infant formula for their bifidogenic (ability to promote the growth of bifidobacteria in the gut) potential, to promote a healthy gut microbiome. An increase in the abundance of beneficial microbiota, such as Lactobacillus  was observed in infants fed infant formula containing GOSs (Yang et al., 2020).