March 2020 Issue

CPE Monthly: The Gut Microbiome and Nutritional Status
By Ana Gabriela Reisdorf, MS, RD, CDE
Today’s Dietitian
Vol. 22, No. 3, P. 42

Suggested CDR Learning Codes: 2070, 2090, 5220, 5280,
Suggested CDR Performance Indicators: 8.1.3, 8.1.4, 8.3.6, 10.4.4
CPE Level 2

Take this course and earn 2 CEUs on our Continuing Education Learning Library

With the initiation of the Human Microbiome Project in 2007, interest in the microorganisms that live within us has skyrocketed. The project initially aimed to document the variety of microbes found on the human body but has expanded to include further evaluation of their impact on our health and longevity. One of the goals of the project is to gain a deeper understanding of human nutritional needs by learning how microbes influence our ability to use nutrients from food.1

Research is discovering that multiple disease states are affected by the microbiome including allergies, autoimmune disease, depression, cognitive decline, obesity, and CVD.2 Between the research stemming from the Microbiome Project and the increased interest in this area of study, scientists have begun to understand more about the impact of the gut microbiome, not just on the development of disease but also on nutritional status. There’s also more of an understanding of how diet, in turn, influences the health of the gut microbiome. Although the exact mechanisms aren’t yet clear, research has begun to identify a complex symbiotic relationship between overall health and the health of the microbiome.

This continuing education course examines the current research on the gut microbiome’s influence on nutritional status. It discusses the relationship between the microbiome and digestion of macro- and micronutrients. It also reviews research related to the gut microbiome and malnutrition and obesity. It’s designed to help dietitians understand the interplay between the microbiome and nutritional status.

What Is the Gut Microbiome?
There are 10 trillion to 100 trillion microbes on the human body, with most living in the gut. The number of microbes that exist on one human body is greater than the number of all the humans who have ever lived. The gut microbiome refers to the collection of bacteria, yeast, and other micro-organisms that live inside the digestive tract.3 With so many microbes living among us, it’s no surprise that they’re intricately connected to our health.

More than 90% of gut microbes belong to one of two general groups of the 70 different phyla that have been identified—Bacteroidetes and Firmicutes.4 And within these two classifications are many different individual species. Most adults have from 400 to 500 species of bacteria in their lower gut or colon at any given time.5 The mouth, stomach, and small intestine have their own unique microbiome. What makes the study of microbes and human health even more complex is that every individual has a unique, diverse set of microbes.

The adult microbiome develops primarily during the first three years of life and is significantly affected by what occurs during this time. The colonization of the gut is initiated during pregnancy. It’s been discovered that the womb isn’t a sterile environment as once believed; bacterial DNA has been found in the placenta, amniotic fluid, and meconium. This means that the maternal microbiome is colonizing and influencing the gut of the fetus. Once the infant is born, the microbiome is further shaped by gestational age, the type of birth (whether by cesarean section or vaginal), breast-feeding vs formula feeding, maternal nutritional status, and the timing of the introduction of solid food.6 By the age of 3, children have fully developed gut microbiomes, similar to what they will have in adulthood.

Although every microbiome is unique and influenced by a variety of factors, families, particularly those who live together, tend to have similar microbiomes. This similarity between family members may be related to a shared environment and a similar diet. Pet ownership seems to increase the amount of the microbiome that’s shared between family members.7

Although most of the microbiome develops early, it can change throughout life. The microbiome is a living organism that can be affected by the type of food it receives and by its environment. In addition, antibiotic use, stress, and illness can modify its composition.

But the microbiome isn’t just influenced by us; it also influences our health. It has several important functions, including assisting with digestion and nutrient absorption as well as modulating immune response. The health of the microbiome can impact one’s risk of developing certain illnesses such as diabetes and autoimmune disease.8

Research in the field of health and the microbiome is only beginning, and the interaction between the human body and the microbes it houses remains complex. Although this field of study is in its infancy, much is known about how diet influences the microbiome and, in turn, how the microbiome influences our body’s ability to use nutrients.

The Microbiome’s Effect on Nutritional Status
The gut microbiome affects the body’s ability to extract and use nutrients from food, but diet also influences the composition and health of the microbiome. Gut bacteria also accomplish the following9:

• help harvest inaccessible nutrients or energy from the diet;
• assist in the synthesis of vitamins;
• support drug metabolism and increase bioavailability;
• assist in gut cell renewal10;
• act as a barrier against gut pathogens; and
• produce short-chain fatty acids.11

Changes in diet can modify the microbiome’s composition in as little as 24 hours, but long-term dietary patterns also seem to determine the general types of microbes found in the gut.12 A study of more than 60 mammalian species found a strong correlation between certain types of microbes and dietary patterns. Carnivores tended to have different gut microbes than those of omnivores or herbivores. Diversity—and thus resilience—of gut microbes was highest among herbivores.13

There have been several studies evaluating the gut microbiomes of different human populations, but it’s hard to determine whether the differences seen among populations are due to dietary patterns, the environment, or other factors.

A 2010 study comparing children in an African village in Burkina Faso with children in Florence, Italy—populations that are considerably different in terms of genetics, environment, and dietary patterns—found significant variations in the gut microbiomes between the groups. The children living in Africa, who were mostly vegetarian and eating a diet high in dense starches such as millet, were found to have more bacteroidetes in the gut. Researchers also discovered that the guts of African children contained prevotella and xylanibacter, known to enable the body to digest plant polysaccharides for energy. These two bacterial strains weren’t found at all in the children living in Italy. Researchers believe the gut microbiome of the African children evolved to help this population extract energy from the indigestible polysaccharides found in their starch-rich diet. Extraction of calories from dense starches wouldn’t be necessary for populations that didn’t consume these types of foods.14

Other studies have evaluated the impact of diet on the microbiome using populations in more similar geographic areas. In a 2012 study, Zimmer and colleagues compared the gut microbiomes of vegetarians, vegans, and omnivores living in Germany. The composition of the microbiome differed depending on the type of diet followed, but the total microbial count remained the same among all study participants. Vegans and vegetarians were found to have greater microbial diversity and more microbes known for carbohydrate fermentation and short-chain fatty acid production, which is expected, since a vegetarian or vegan diet tends to be higher in carbohydrates.15 Other studies haven’t duplicated these findings. A 2016 observational study by Wu and colleagues found no differences between the gut microbiota of vegans vs omnivores when they lived in the same environment.16

But just as long-term dietary patterns can influence the gut microbiome, so can immediate diet modifications. A 2014 study by David and colleagues found that shifts from an omnivorous to a plant-based diet altered gut microbiota composition in as little as five days. When subjects ate an animal-based diet with very little carbohydrate or fiber, gut bacteria shifted to be more similar to that of other carnivorous mammals, while the opposite occurred when subjects ate a plant-based diet. Consumption of the animal-based diet resulted in an increase in bile-tolerant microbes and a decrease in those able to ferment carbohydrates. The opposite was true when subjects consumed a plant-based diet—the type of microbes shifted to increase carbohydrate fermentation. Based on the results of this study, it’s clear that both dietary patterns and diet modifications can affect the composition of the gut microbiome relatively quickly.12

Macronutrients and the Microbiome
The gut microbiome doesn’t only change with a shift from an omnivorous to a vegetarian or vegan diet; modification of macronutrient ratios also can influence gut microbes. However, it’s challenging to study the impact of a specific macronutrient in isolation because a decrease in one results in an immediate increase in another.

In general, those who consume a high-carbohydrate diet tend to have an enterotype, or bacterial classification that contains more prevotella, whereas those who eat a higher-fat or -protein diet tend to have more bacteroides. Prevotella has been linked to improved glucose tolerance but also to increased inflammation.16

The type of fat in the diet also seems to influence the type and function of the gut microbes, but human research isn’t yet available. A 2015 animal study found that mice fed lard had increased inflammation markers, exacerbated by gut bacteria, whereas those fed fish oil, which is higher in anti-inflammatory omega-3 fatty acids, showed lower inflammation and less metabolic dysfunction.17 The results of this study likely are due to the ability of certain gut microbiota to facilitate absorption of lipids by increasing the size and number of lipid droplets, which, in turn, increases inflammation.18

The impact of protein on gut bacteria is unclear. A 2011 study evaluated the effect of a high-protein diet on total gut bacteria. Obese men consuming a high-protein, weight-loss diet had a significant decrease in total gut bacteria, specifically butyrate-producing organisms. Researchers couldn’t determine whether the decrease in gut bacteria was caused by the higher protein intake or by the lower carbohydrate intake. But upon examination of fecal metabolites, those on the high-protein diets were shown to have an increase in certain compounds that indicate a shift to microbial protein fermentation. The metabolites resulting from protein fermentation have been correlated with an increase in inflammation and risk of colorectal cancer.19

The type of carbohydrate consumed seems to have significantly different effects on the gut microbiome. Humans don’t have the enzymes to break down and digest many dietary carbohydrates, so gut bacteria may be beneficial by using the fibers humans can’t digest for energy. A 2016 study by Sonnenburg and colleagues evaluated the importance of carbohydrates that are easily digested by microbes by studying germ-free mice. The mice’s digestive tracts were populated with a human fecal sample, and the mice were put on a high- or low-carbohydrate diet. After seven weeks, mice on the low-carbohydrate diet had 60% fewer microbial strains in the gut compared with those fed the high-carbohydrate diet.20 Other studies also found that low-carbohydrate diets lead to a decrease in certain types of gut bacteria, particularly those that produce butyrate. These findings are significant for human health because low levels of butyrate-producing bacteria in the gut have been linked to an increased risk of inflammation and poor gut-barrier function. The opposite also is true; a study of obese subjects found that a low-calorie diet including a fiber supplement increased bacterial diversity by 25%.21 This research suggests that carbohydrates in the diet encourage the growth of gut-protective bacteria.

In summary, carbohydrates, particularly in the form of fermentable fibers, seem to be beneficial. Also, the type of fat consumed also can trigger an inflammatory or anti-inflammatory response within the gut microbiome. Although the microbiome can be affected by short-term dietary changes, long-term patterns seem to have the greater influence in determining what type of bacteria is present.

Micronutrients and the Microbiome
The gut microbiome influences the body’s ability to use and absorb micronutrients from food. The example of this connection that’s probably most familiar to RDs is vitamin K. It’s routine to give a vitamin K injection to newborns at birth to prevent hemorrhage. Infants are born with a low concentration of vitamin K–producing bacteria in the gut and may not have an adequate supply for blood clotting. Over time, gut bacteria are able to start producing adequate amounts of vitamin K.

But the role of gut bacteria in micronutrient status isn’t just limited to vitamin K. Bacteria can synthesize vitamin B12, vitamin B6, pantothenic acid, niacin, biotin, and folate.22 These various vitamins are either byproducts of fermentation or are excreted by the gut bacteria. The ability to produce these important vitamins may help humans maintain adequate levels of them.

The microbiome also affects the absorption of certain minerals. For example, iron, a necessary mineral for almost all living species, interacts extensively with gut bacteria. Free iron is scarce in the gut, so microbes must compete for the iron that’s available. Pathogenic bacteria have greater iron needs than do beneficial bacteria. Since iron is limited, the scarcity of this important mineral slows the growth of pathogenic bacteria. In developing countries where people are more susceptible to infectious diseases, low hygiene, and gut inflammation, there’s an increase in morbidity and mortality with iron supplementation, particularly in children. It’s believed that supplemental iron administration enables pathogenic bacteria to thrive in an already compromised gut.23

The gut microbiome also influences the absorption and utilization of phytonutrients, plant compounds that are beneficial to health and don’t fall into the category of micronutrients. These include compounds such as terpenoids, chlorophylls, and polyphenols. Phytonutrients have antioxidant properties and are thought to be critical for preventing disease. In general, phytonutrients aren’t well absorbed in the digestive tract, but certain gut bacteria may help improve absorption by breaking down these substances into smaller components or converting them into absorbable substances.24 However, further research is needed to evaluate the complex interaction between phytonutrients and the microbiome.

Without gut microbes, humans may be at risk of developing vitamin and mineral deficiencies and also would lose the benefit of many antioxidants due to the inability to efficiently digest and absorb phytonutrients. The gut microbiome assists in the absorption of these important nutrients, improving nutritional status and health.

The Microbiome and Malnutrition
Undernutrition, common in many countries, is responsible for approximately 45% of childhood deaths.25 Based on observations of nutritional status from developing countries, malnutrition isn’t always simply a result of inadequate calories; there can be nourished and undernourished children living in the same household. One reason this discrepancy may occur is that the gut microbiome influences the risk of malnutrition.26

A 2013 study of monozygotic and dizygotic twins in Malawi aimed to evaluate the impact of the gut microbiome on kwashiorkor. Researchers studied 317 twin pairs in their first three years of life. One-half of the twins remained well nourished during the study period, but in 43% of the twin pairs, at least one sibling developed malnutrition. In 7% of the twin pairs, both siblings were diagnosed with kwashiorkor.27

The children who developed malnutrition were treated with a peanut-based, ready-to-use therapeutic food, resulting in improvement. Their gut microbiomes were evaluated before and after the treatment. Those with malnutrition were found to have poor gut maturation and a lack of diversity and supportive bacteria, indicating a dysfunctional gut microbiome. The guts of the children matured during treatment with the therapeutic food but regressed once the treatment ended.27

After the study was completed, frozen fecal samples from the children with malnutrition were transplanted into germ-free mice. When fed a typical Malawian diet, the mice experienced significant weight loss and disruptions in protein and carbohydrate metabolism. The results of this study indicate that the gut microbiome may be responsible for the differences in nutritional status between children within the same household, particularly in developing countries.27

A smaller study of healthy vs malnourished children in Bangladesh also evaluated the impact of the gut microbiome on nutritional status. Fecal samples were collected from seven healthy and seven malnourished children between the ages of 2 and 3. The samples were then evaluated, and healthy children were found to have significantly greater gut microbiota diversity when compared with malnourished children. The healthy children also had more of the Bacteroidetes and Firmicutes strains; each of these phyla composed approximately 44% of their microbiomes. On the other hand, the microbiomes of the malnourished children were 18% bacteroidetes and 32% firmicutes. The microbiomes of the malnourished children were composed of 46% proteobacteria, compared with only 5% in the healthy children. The malnourished children also were more likely to have more pathogenic bacteria, such as enterobacteria, present in their guts.28

The type of bacteria found in the gut is believed to be important in determining nutritional status. Bacteroidetes are generally responsible for the breakdown of complex fibers and the synthesis of short-chain fatty acids. They can help extract energy from a variety of foods. Firmicutes have been indicated to influence calorie absorption. A microbiome with reduced quantities of these particular strains may decrease calorie absorption and cause malnutrition even when adequate calories are consumed.28

In addition, pathogenic bacteria in the subjects with malnutrition indicate the presence of subclinical infections of the gastrointestinal tract, which may, in turn, result in poor nutrient absorption and worsening malnutrition. The authors of this study mention that other studies involving malnourished children haven’t found the same phyla to be universally dominant or problematic, meaning that environment, food, and geography may play a role in determining which bacteria are harmful and which can trigger malnutrition.28

A 2011 review by Kau and colleagues suggests that it may not be a specific type of bacteria that’s the cause of malnutrition, but rather an interaction between these microbes and certain environmental triggers within a susceptible host that becomes inflammatory, triggering malnutrition and other related illnesses.22 Further research is needed to identify which specific bacterial strains increase susceptibility to malnutrition. At this time, there’s an understanding that the gut microbiome is just one piece of a complex puzzle also involving the environment, the host, and diet.

Obesity and the Microbiome
Obesity is a serious health concern affecting almost 40% of the population in the United States, according to the Centers for Disease Control and Prevention.29 There are many causes of obesity, but recent research has found that the microbiome may play a role in increasing risk.

It’s believed that the gut microbiome influences obesity in several ways, but the research in this area remains complex. The first theory is that excessive energy is harvested by gut microbiomes, resulting in an increased production of short-chain fatty acids. These fatty acids, in turn, promote fat deposition, lead to an overexpression of obesity-related genes, or cause an increase in the endotoxin lipopolysaccharide, which triggers inflammation and obesity.30 A combination of these factors working together may increase the risk of obesity for people with a specific microbiome profile. The exact profile of the “obese” microbiome still is unknown, but there are a handful of studies with interesting results.

In a 2009 study by Turnbaugh and colleagues, researchers evaluated the gut microbiomes of 154 lean and obese mono- and dizygotic twin pairs and their mothers. The microbiomes were found to be similar among family members, but variations among individuals were identified. Subjects who were obese had phylum-level changes to their microbiomes and less bacterial diversity compared with lean subjects.31

Another theory about how the microbiome influences obesity is that there are certain types of bacteria that can extract additional calories from food. A 2006 study by Turnbaugh and colleagues found that the balance of the two dominant phyla, Bacteroidetes and Firmicutes, was different in obese subjects than in lean subjects. This resulted in an increased capacity to harvest more calories from the diet, causing weight gain and increased fat deposition.32

It’s also unclear whether changes in diet over the last 50 years—the overall increase of calorie and refined carbohydrate intake—has modified the gut microbiome in a way that increases risk of obesity. It’s clear that diet influences the composition of the gut microbiome. A 2013 study by Cotillard and colleagues found that a calorie-controlled weight loss diet increased microbial gene richness and lowered systemic inflammation.21 This research suggests that excess calories could be an underlying cause of the low diversity of gut microbiota in obese individuals. Other studies have found that the macronutrient composition of the diet is correlated with specific bacterial strains, meaning diet likely has an impact on shaping the microbiome.33

Given the theory that bacterial imbalance and a lack of diversity may lead to an increased risk of obesity, the question arises as to whether supplementation with probiotics could reduce obesity. Although this research is still in its infancy, a handful of animal studies have shown interesting results. A 2006 study of obese mice found that Lactobacillus rhamnosus PL60 reduced weight and adipose tissue without calorie reduction.34 Another similar study found that a different bacterial strain, Lactobacillus paracasei, also decreased fat storage by modulating the effects of ANGPTL4, which controls triglyceride deposition into fat cells.35 These results seem to be strain specific, and there’s no current research that has identified which particular strains may help reduce obesity in humans. Given the diversity of the microbiome among individuals, research is still many years away from identifying strains to decrease obesity across all population groups.

Role of RDs
Although much of the research on the gut microbiome and nutritional status is in its infancy, the potential therapeutic benefits of probiotics are of great interest. At this time, there are no specific evidence-based recommendations for the strain or dosage of probiotics to use to treat malnutrition or obesity. Nevertheless, RDs can make a few recommendations.

The first is to suggest the use of prebiotics for those struggling with digestive concerns or bacterial imbalance. These would include fermentable fibers such as inulin, galactooligosaccharides, fructooligosaccharides, and lactulose. These foods have been found to shift the composition of the gut microbiome to encourage the growth of the most beneficial species.36 A 2007 study found that when mice on a high-fat diet were given prebiotics, the amount of bifidobacteria increased and inflammation to the digestive tract decreased.37 Foods such as dandelion greens, garlic, and chicory root are high in these beneficial prebiotic fibers. These types of foods may be considered for those with digestive concerns who aren’t sensitive to fermentable carbohydrates.

The research on specific probiotic strains to improve nutritional status still is emerging, so evidence-based recommendations for dietary supplements can’t be made. But fermented foods, such as sauerkraut, kimchi, or yogurt, may be considered as a helpful source of beneficial bacteria for those interested in supporting their microbiomes and immune systems.38

It’s clear that the microbiome has a significant influence on human health, well-being, and nutritional status. But the relationship is complex and difficult to discern due to the variety of bacterial strains, dietary patterns, and environmental conditions. At this time, there’s simply not enough evidence to make specific recommendations on strains or dosages.

— Ana Gabriela Reisdorf, MS, RD, CDE, is a Franklin, Tennessee–based nutrition consultant and writer.

Learning Objectives

After completing this continuing education course, nutrition professionals should be better able to:
1. Describe what the gut microbiome is.
2. Distinguish the impact of the microbiome on overall nutritional status.
3. Translate the role of the gut microbiome in digestion and absorption of macro- and micronutrients.
4. Assess how the microbiome influences malnutrition and obesity.

CPE Monthly Examination

1. Where are most of the microbes in the body located?
a. Throughout the digestive system
b. Spread evenly all over the body
c. Only in the colon
d. Not in one specific place

2. The two major classes of bacteria that live in the gut are which of the following?
a. Lactobacillus and E coli
b. Cyanobacteria and acidobacteria
c. Bacteroidetes and firmicutes
d. Deferribacteres and fusobacteria

3. Changes to the microbiome caused by dietary modifications can occur:
a. In as little as 24 hours.
b. Only after eliminating meat.
c. When dietary fat is increased.
d. After a year of following a diet.

4. The microbiome of an individual on a high-starch diet likely would have more of which of the following bacteria?
a. Lactobacillus and firmicutes
b. Prevotella and xylanibacter
c. Bacteroidetes and xylanibacter
d. Firmicutes and prevotella

5. A high-protein diet will decrease which of the following?
a. The diversity of the microbiome
b. The overall number of gut bacteria
c. Only the number of bacteroidetes
d. Only the number of firmicutes

6. Low levels of butyrate-producing microbes:
a. Lower inflammation and improve digestion.
b. Improve gut permeability and nutrient absorption.
c. Are a risk factor for weight gain.
d. Increase inflammation and gut permeability.

7. When given supplemental iron, a compromised gut will do which of the following?
a. Thrive, and the risk of infection will decrease
b. Start to absorb more iron, leading to iron toxicity
c. Do nothing and excrete the iron
d. Increase risk of pathogenic infection

8. When malnourished children are treated for malnutrition, their microbiome will do which of the following?
a. Improve, but then regress once treatment ends
b. Improve permanently and fully mature
c. Not change at all and have no impact on health
d. Increase in diversity and improve nutritional status

9. Malnourished children are more likely to have which of the following types of gut bacteria when compared with healthy children?
a. Lactobacillus and proteobacteria
b. Bacteroidetes and cyanobacteria
c. Enterobacteria and proteobacteria
d. Firmicutes and actinobacteria

10. The type of microbiome that increases risk of obesity has which of the following properties?
a. Low in bacterial diversity and consists of different types of bacteria than those of lean people
b. High in bacterial diversity and the same types of bacteria as those of lean people
c. High in bacterial diversity but has different types of bacteria than those of lean people
d. Low in bacterial diversity but has similar types of bacteria as those of lean people

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