Information

Can you change your gut microbiota by changing your diet? Would that affect calorie uptake?


I have seen peer-reviewed papers mentioning the daily changes in gut microbiota composition according to dietary changes. See for example this paper:

http://genomebiology.com/2014/15/7/R89

My question is related to this one:

Relationship between our microbiome and personalized nutrition

If, according to these recently published scientific results, it takes a day to change the gut microbiota to adjust to the dietary change, and the presence of certain microbes makes food assimilation more effective,

Does this mean that alternating a protein-rich meat and dairy diet with a carbs-rich diet every day would make our microbiota switch daily and not have time to increase calorie uptake?


Firstly, it should be noted that a stable, healthy microbiome is generally thought to be a marker of health; actively disrupting it through diet in an attempt to fight with it over nutrients is therefore not necessarily a good idea, as it can affect the health of not only your gut but also your immune system, etc.

Dysfunctional microbiomes are for example associated with behavioral problems in eating disorders.

Nonetheless, diet shifts have been used as a tool to attempt to control the microbiome and put it in a "healthy state". You can indeed use consumption of some foods to shift microbiome composition. Presumably if you did this in a sufficiently disjointed way, you could throw your microbiome into a sort of ecological chaos.

However, it would be much simpler to just constantly take antibiotics to ensure that your gut load of microbes was generally low. This still isn't a good idea, as it can lead to Clostridium difficile or E. coli infections or other bad things, but it would be a much more straightforward way of getting to the desired end state.


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Methods

We performed a systematic literature review in September 2015 by searching the electronic MEDLINE database via PubMed. Search terms included combinations of the terms “microbiota”, “intestinal mucosa/microbiology”, “gastrointestinal tract/microbiology”, “gastrointestinal diseases/microbiology”, with “diet”, “food”, “polysaccharides”, “carbohydrates”, “proteins”, “meat”, “fat”, “lactose”, “oligofructose”, “prebiotics”, “probiotics”, “polyphenols”, “starch”, “soy”, “sucrose”, “fructose”, “diet, vegetarian”, “diet, western”, “cereals”, “dietary fiber”, and “dietary supplements”. Articles were reviewed independently by two investigators, R.K.S. and K.M.L, and this was adjudicated by W.L. We limited our search to articles available in English, human studies, and those published between 1970 and 2015. We excluded studies that did not explicitly address the effect of a dietary intervention on microbial composition. Manual searches through reference lists of the articles were also performed to identify additional studies. This resulted in a total of 188 articles being selected for inclusion in this review. Studies describing the relationship between specific dietary components and intestinal microbiota composition ranged from subject number n = 3 to n = 344, with a majority of studies clustered around subject number n = 20 to 70. Study designs were primarily randomized controlled trials, cross-sectional studies, case–control studies, and in vitro studies. In addition to human studies, several animal studies were also included to demonstrate dietary impact on the microbiome under controlled experimental conditions.


Future work

Several studies have investigated the role of gut microbiota in many diseases, including colorectal cancer, liver disease, and others (Dicksved et al., 2009 Yang et al., 2009 Claud et al., 2013 Couturier-Maillard et al., 2013 Udayappan et al., 2014 Llopis et al., 2014 Buie, 2015). In the last few years, gut microbiota has been studied using metagenomic methodologies (Qin et al., 2010). Zheng et al. (2019) reported that the gut microbiome from patients with schizophrenia might be relevant to pathology of schizophrenia via altering neurochemistry and neurologic function. Currently, methods of modulating gut microbiota, including FMT, probiotics, and prebiotics, have come to be considered suitable treatment options for these diseases.

Future studies of probiotics and prebiotics should focus on the effect on different diseases with an agreement regarding the doses and the kind of bacteria used under each set of pathological conditions. High-throughput technologies allow researchers to easily find answers to many questions surrounding probiotics and prebiotics. This may help us to design new probiotics that more efficient with a higher quality and may lead to find new bacterial strains with probiotics properties.

Many studies have confirmed the ability of the gut microbiota to modify the expression of the host genes, and the impact of microbiota on miRNA expression was discovered using miRNA arrays, supporting the fact that gut microbiota affects the expression of hundreds of genes in the host (Dalmasso et al., 2011 Watson & Hall, 2013). More studies are needed to understand miRNA-microbiota interactions and determine which kinds of microbiota can modulate miRNA expression by combining high-throughput technologies.

Recently, FMT has been found to be a perfect treatment for rCDI cases that are nonresponsive to antibiotic therapy. Its high efficiency in many diseases has been confirmed, but FMT treatment suffers from a lack of information about the safety of long- and short-term administration. More and safer synthetic bacteria products (e.g., encapsulated formulations and full-spectrum stool-based products) and methods of transplantation need be developed to make FMT easier to use and more acceptable to patients. SER109, the mixture of bacterial spores, has shown high efficiency with rCDI diarrhea, and other similar products are being developed. The synthetic bacteria products may be able to replace traditional fecal treatment. In the future, various bacterial products may contain complicated mixtures of different bacterial species tailored using microbial ecological principles, and doctors may choose the suitable synthetic bacteria mixtures to a specific disease. FMT, probiotics, and other treatments meant to modulate a healthy microbiota may come to be considered suitable alternative treatments to antibiotics for diseases related to imbalances of gut microbiota.


Current Status of Knowledge

How do changes in dietary sugars and sweeteners redefine the microbial habitats of the gut?

The gut microbiome is defined as the assemblage of microbes and their habitat ( 19). For the gut, this environment is established by the host's genetics and external environmental factors, which includes diet. While the host's species identity exercises significant control over the microbiome ( 20, 21), within a specific host, environmental factors are the dominant controllers of microbiome composition ( 22, 23). Diet has been demonstrated to be capable of restructuring the microbiome within days, yet is typically reversible on a similar timescale ( 22, 24–26). Of the macronutrients, carbohydrates and nitrogen sources have been demonstrated to be the most influential ( 18, 27–29), and simple sugars can override host genetic effects on the microbiome ( 30).

Roughly 48% of the caloric intake in the American diet is carbohydrates ( 31), with 13% coming from added sugars ( 32). Modern types of added sugars and sweeteners in the Western world are naturally occurring oligosaccharides, sugar alcohols, and glycosides as well as synthetic sugars. Additionally, some natural and artificial sweeteners do not contain sugar moieties but comprise peptides or other molecules. Termed low-calorie sweeteners, these are nonnutritive or low calorie due to a combination of being poorly metabolized (sugar alcohols and some of the intense sweeteners) in the human body and/or providing the effective sweetness of sucrose at very low doses (intense sweeteners). For simplicity, we refer to compounds with sugar moieties as sugars (oligosaccharides, sugar alcohols, and glycosides) and others as sweeteners. The major sugars and sweeteners consumed in America today are displayed in Table 1, and further details are shown in Supplemental Table 1 . Notably, in the past 50 y, several novel sweeteners have been created and other natural sugars have been supplemented into foods ( Figure 1).

These additions not only changed the types and amount of the sugars and sweeteners Americans consume, but also reduced the consumption of sucrose. Concurrent with research in biochemistry and the nutritional sciences, the microbiome field must assess the effects of these sugars and sugar substitutes on human physiology via alterations in the structure and/or function of the gut microbiome.

Consumption trends for common dietary sugars and sweeteners in the United States. Food manufacturers are not required to report the amount of sweeteners in food. Here, intake amounts are estimated where limited data are available (dark lines and points) and hindcasted (transparent lines) where no data are available. Consumption data for refined cane and beet sugar, high-fructose corn syrup, and other sugars/sweeteners were acquired from the US Food and Agriculture Economic Research Service ( 33). Estimated consumption for acesulfame potassium, aspartame, erythritol, saccharin, stevia, and sucralose were calculated from the percentage of adult Americans consuming low-calorie products ( 34, 35) multiplied by the market share of the sweetener ( 36–43) multiplied by the daily amount consumed for a 62-kg individual ( Table 1). The hindcasted amount for trehalose was based on anticipated usage ( 44). All other hindcasted values are the average of estimated intake to illustrate the years these products were used as food additives.

Consumption trends for common dietary sugars and sweeteners in the United States. Food manufacturers are not required to report the amount of sweeteners in food. Here, intake amounts are estimated where limited data are available (dark lines and points) and hindcasted (transparent lines) where no data are available. Consumption data for refined cane and beet sugar, high-fructose corn syrup, and other sugars/sweeteners were acquired from the US Food and Agriculture Economic Research Service ( 33). Estimated consumption for acesulfame potassium, aspartame, erythritol, saccharin, stevia, and sucralose were calculated from the percentage of adult Americans consuming low-calorie products ( 34, 35) multiplied by the market share of the sweetener ( 36–43) multiplied by the daily amount consumed for a 62-kg individual ( Table 1). The hindcasted amount for trehalose was based on anticipated usage ( 44). All other hindcasted values are the average of estimated intake to illustrate the years these products were used as food additives.

Usage and absorption of common dietary sugars and sweeteners in the United States 1

Sugar/sweetener . Date first approved for use in the US . Single-serving amount . Daily consumption per kilogram body weight . Percentage (%) absorbed or consumed in small intestine . Percentage (%) absorbed or consumed in large intestine . Percentage (%) in feces .
Sucrose NA 35 g 1–2 g >95 <5 <1
High-fructose corn syrup-55 1970 30 g 1–2 g See fructose and glucose fructose absorption increases with glucose co-consumption See fructose and glucose See fructose and glucose
Glucose NA 25 g 1–2 g >95 <5 <1
Fructose NA 25 g 1–2 g 90 10 <1
Trehalose 2000 3 g 0.5 g >20 Not reported Not reported
Sorbitol 1972 2–90 g <1 g 25 75 <1
Erythritol 1996 500 mg–10 g <1 g 90 10 <7
Xylitol 1960 300 mg–1 g <1 g 50 50 1
Mannitol 1950 40 mg 35 mg 25 75 <3
Stevia (Rebaudio-side A) 2008 30 mg 2 mg 60% between the small and large intestine 60% between the small and large intestine 5% as steviol
Aspartame 1981 120 mg 8.7 mg 70% of methanol 85% of phenylalanine >95% of aspartic acid 30% of methanol 13% of phenylalanine <3% of aspartic acid 0% of methanol 2% of phenylalanine 2% of aspartic acid
Saccharin (benzoic sulfimide) 1959 usage limited 1972–1977 30 mg <5 mg 95 Not reported 3
Sucralose 1998 40 mg 1.6 mg 10–30 Not reported 70–90
Acesulfame potassium 1988 30 mg 5 mg 95 Not reported Not reported
Sugar/sweetener . Date first approved for use in the US . Single-serving amount . Daily consumption per kilogram body weight . Percentage (%) absorbed or consumed in small intestine . Percentage (%) absorbed or consumed in large intestine . Percentage (%) in feces .
Sucrose NA 35 g 1–2 g >95 <5 <1
High-fructose corn syrup-55 1970 30 g 1–2 g See fructose and glucose fructose absorption increases with glucose co-consumption See fructose and glucose See fructose and glucose
Glucose NA 25 g 1–2 g >95 <5 <1
Fructose NA 25 g 1–2 g 90 10 <1
Trehalose 2000 3 g 0.5 g >20 Not reported Not reported
Sorbitol 1972 2–90 g <1 g 25 75 <1
Erythritol 1996 500 mg–10 g <1 g 90 10 <7
Xylitol 1960 300 mg–1 g <1 g 50 50 1
Mannitol 1950 40 mg 35 mg 25 75 <3
Stevia (Rebaudio-side A) 2008 30 mg 2 mg 60% between the small and large intestine 60% between the small and large intestine 5% as steviol
Aspartame 1981 120 mg 8.7 mg 70% of methanol 85% of phenylalanine >95% of aspartic acid 30% of methanol 13% of phenylalanine <3% of aspartic acid 0% of methanol 2% of phenylalanine 2% of aspartic acid
Saccharin (benzoic sulfimide) 1959 usage limited 1972–1977 30 mg <5 mg 95 Not reported 3
Sucralose 1998 40 mg 1.6 mg 10–30 Not reported 70–90
Acesulfame potassium 1988 30 mg 5 mg 95 Not reported Not reported

Full information and references are provided in Supplemental Table 1 . NA, not applicable.

Usage and absorption of common dietary sugars and sweeteners in the United States 1

Sugar/sweetener . Date first approved for use in the US . Single-serving amount . Daily consumption per kilogram body weight . Percentage (%) absorbed or consumed in small intestine . Percentage (%) absorbed or consumed in large intestine . Percentage (%) in feces .
Sucrose NA 35 g 1–2 g >95 <5 <1
High-fructose corn syrup-55 1970 30 g 1–2 g See fructose and glucose fructose absorption increases with glucose co-consumption See fructose and glucose See fructose and glucose
Glucose NA 25 g 1–2 g >95 <5 <1
Fructose NA 25 g 1–2 g 90 10 <1
Trehalose 2000 3 g 0.5 g >20 Not reported Not reported
Sorbitol 1972 2–90 g <1 g 25 75 <1
Erythritol 1996 500 mg–10 g <1 g 90 10 <7
Xylitol 1960 300 mg–1 g <1 g 50 50 1
Mannitol 1950 40 mg 35 mg 25 75 <3
Stevia (Rebaudio-side A) 2008 30 mg 2 mg 60% between the small and large intestine 60% between the small and large intestine 5% as steviol
Aspartame 1981 120 mg 8.7 mg 70% of methanol 85% of phenylalanine >95% of aspartic acid 30% of methanol 13% of phenylalanine <3% of aspartic acid 0% of methanol 2% of phenylalanine 2% of aspartic acid
Saccharin (benzoic sulfimide) 1959 usage limited 1972–1977 30 mg <5 mg 95 Not reported 3
Sucralose 1998 40 mg 1.6 mg 10–30 Not reported 70–90
Acesulfame potassium 1988 30 mg 5 mg 95 Not reported Not reported
Sugar/sweetener . Date first approved for use in the US . Single-serving amount . Daily consumption per kilogram body weight . Percentage (%) absorbed or consumed in small intestine . Percentage (%) absorbed or consumed in large intestine . Percentage (%) in feces .
Sucrose NA 35 g 1–2 g >95 <5 <1
High-fructose corn syrup-55 1970 30 g 1–2 g See fructose and glucose fructose absorption increases with glucose co-consumption See fructose and glucose See fructose and glucose
Glucose NA 25 g 1–2 g >95 <5 <1
Fructose NA 25 g 1–2 g 90 10 <1
Trehalose 2000 3 g 0.5 g >20 Not reported Not reported
Sorbitol 1972 2–90 g <1 g 25 75 <1
Erythritol 1996 500 mg–10 g <1 g 90 10 <7
Xylitol 1960 300 mg–1 g <1 g 50 50 1
Mannitol 1950 40 mg 35 mg 25 75 <3
Stevia (Rebaudio-side A) 2008 30 mg 2 mg 60% between the small and large intestine 60% between the small and large intestine 5% as steviol
Aspartame 1981 120 mg 8.7 mg 70% of methanol 85% of phenylalanine >95% of aspartic acid 30% of methanol 13% of phenylalanine <3% of aspartic acid 0% of methanol 2% of phenylalanine 2% of aspartic acid
Saccharin (benzoic sulfimide) 1959 usage limited 1972–1977 30 mg <5 mg 95 Not reported 3
Sucralose 1998 40 mg 1.6 mg 10–30 Not reported 70–90
Acesulfame potassium 1988 30 mg 5 mg 95 Not reported Not reported

Full information and references are provided in Supplemental Table 1 . NA, not applicable.

The effect of sugars on microbial physiology has been a cornerstone of microbiology. Catabolite repression was initially discovered through the observation that in the presence of glucose, some nonglucose metabolizing enzymes are suppressed ( 45). This observation was later extended to other carbohydrate sources ( 46, 47), with the overall assumption that in the presence of a more energy efficient nutrient source, cells conserve energy by turning off other costlier metabolic pathways. Recent single-cell studies have expanded this concept and demonstrated that this metabolic switch is determined on a per cell basis rather than at the community level ( 48). These foundational works imply that microbial metabolic activities can change immediately in response to the introduction of a novel sugar. As we discuss subsequently, this immediate response posits microbes for additional avenues of adaptation, whether by changing their population size or by genetically diversifying.

The behavior of microbes in response to sugar is more complex and difficult to predict and study in the gut than in culture. Microbial exposure to sugars and sweeteners varies along the intestinal tract as a result of how readily each sugar/sweetener is absorbed by the host ( Table 1, Supplemental Table 1 ). Most sugars and sweeteners are actively absorbed in the small intestine through sugar transporters, resulting in only 5–30% of these sugars and sweeteners reaching the large intestine ( 49). Consequently, the small intestinal gut environment is enriched ∼10-fold in sugars and sweeteners compared with that in the large intestine. These available sugars appear to be important substrates for microbes in the small intestine as small intestinal microbes are enriched in carbohydrate uptake and utilization genes and transcripts with respect to microbes in the large intestine ( 50).

Sugars and sweeteners are not absent in the large intestine, however. Fructose, sugar alcohols, and some sweeteners (e.g., sucralose) are passively, slowly, or very poorly absorbed in the small intestine ( Table 1, Supplemental Table 1 ). Up to 30–90% of these sugars and sweeteners pass into the large intestine. Furthermore, overconsumption of these sugars and sweeteners readily results in malabsorption and overflow to the large intestine. The exact amounts of sugars/sweeteners that reach the large intestine, however, is difficult to generalize across individuals. Individuals (and females compared with males) display considerable variation in their absorptive capacity for a sweetener or sugar ( 51–56). Notably, the fructose transporter termed glucose transporter (GLUT) type 5 (GLUT5) is not present in infants ( 57), and in adults, its absorption is enhanced in a dose-dependent manner in the presence of glucose ( 58). Moreover, the small intestine adapts to repeated sugar ingestion by increasing the expression of sugar transporters, hydrolases, and other catabolic enzymes ( 59–61). In addition, complex sugars/sweeteners are broken down into simpler compounds by the host or by gut microbes, thereby adding an extra layer of complexity to the total profile of nutrients available to gut microbes. As a result, the concentration of sugars/sweeteners in the gut is not a simple product of what the host consumes, but rather is dependent on the individual host's absorptive capabilities and the metabolic activities of gut microbes. Therefore, we cannot assume a single profile of sugars/sweeteners in the gut but must instead consider concentration gradients of each sugar/sweetener throughout the gut ( Figure 2).

Absolute (A) and fractional amounts (B) of common dietary sugars and sweeteners in the SI and LI and in feces. Data assume all sugars/sweeteners are consumed at once in the amounts estimated for a single serving for a 62-kg individual. The amount/fraction of trehalose, erythritol, and acesulfame potassium in feces is unknown. We predict that 10% of these sugars/sweeteners are present in the LI and 90% in the SI. For (B), the stacked bar plots for SI, LI, and feces directly above the label are calculated fractional amounts. The additional bar plots on one or both sides of these central bar plots illustrate gradients of sugars/sweeteners in the intestinal tract. These gradients are estimated amounts in the transition between the different regions of the intestinal tract, which are separated by thick white lines. Differences among the SI, LI, and feces reflect differences in the host absorption and microbial consumption of these sugars/sweeteners along the intestinal tract ( Table 1). LI, large intestine SI, small intestine.

Absolute (A) and fractional amounts (B) of common dietary sugars and sweeteners in the SI and LI and in feces. Data assume all sugars/sweeteners are consumed at once in the amounts estimated for a single serving for a 62-kg individual. The amount/fraction of trehalose, erythritol, and acesulfame potassium in feces is unknown. We predict that 10% of these sugars/sweeteners are present in the LI and 90% in the SI. For (B), the stacked bar plots for SI, LI, and feces directly above the label are calculated fractional amounts. The additional bar plots on one or both sides of these central bar plots illustrate gradients of sugars/sweeteners in the intestinal tract. These gradients are estimated amounts in the transition between the different regions of the intestinal tract, which are separated by thick white lines. Differences among the SI, LI, and feces reflect differences in the host absorption and microbial consumption of these sugars/sweeteners along the intestinal tract ( Table 1). LI, large intestine SI, small intestine.

How are microbes altered by changes in dietary sugars and sweeteners?

Summing over the complexity of host sugar/sweetener absorption, microbial products, and varying intestinal conditions produces a surfeit of gut microenvironments along the intestinal tract. In the Restaurant Hypothesis ( 62), each of these environments can be thought of as a restaurant serving different foods. A microbe thrives in the environment that best meets its nutrient and environmental needs, its niche [as defined by Hutchinson ( 63)], and presents the least competition from other microbes. The gastrointestinal tract is not a homogenous microbial culture, but rather displays biogeography ( 64), whereby different microbial communities exist at distinct gut locations. We propose that microbial habitation in these different microenvironments (restaurants) contributes to the observed biogeography of the gut. In other words, the variation in microbes found along the gut is dependent on the variation in sugars/sweeteners present along the gut.

Importantly, this hypothesis leads to an additional postulate, namely that the same microbe could exist in multiple, different, spatially separated microenvironments. To best utilize each microenvironment, the same microbe may require different regulatory, metabolic, and genetic adaptations. Pathobionts may be the result of such adaptations: these are commensal organisms that, while normally benign, become pathogenic under specific host conditions or at specific gut locations ( 65). As any microbe can be functionally altered by the local gut environment, we suggest the term “microbial biogeographical identities” as a generalization. Here we use this concept to discuss the mechanisms of adaptation, the resulting microbial products, and the potentially altered host interactions resulting from different microenvironments.

Specifically, changes to the sugar/sweetener pool in the gut lead to 3 mutually inclusive predictions regarding the effect on microbes ( Figure 3). First, microbes can differentially regulate their metabolic networks to accommodate altered microenvironments via catabolite repression or other regulatory pathways. Transcriptomics and metabolomics have the capacity to capture these signatures of dietary change. Second, transcriptional changes and the availability of carbon substrates can alter which microbes are present and their abundance in each microenvironment. Such changes manifest as microbial community compositional shifts typically analyzed by 16S ribosomal RNA gene sequencing. Third, microbes can genetically adapt to altered conditions to maximize use of the new microenvironments, akin to the selection of antimicrobial resistance. As we discuss in the following, strain variation is rarely studied, but in studies designed to detect such events, genetic adaptation is observed.

Changes in sugar and sweetener consumption lead to 1) transcriptional, 2) compositional, and/or 3) genetic changes in gut microbes. The colored bar plots represent illustrative fractional compositions of sugars/sweeteners in the gut. 1) In response to a changed set of dietary sugars/sweeteners, microbes can alter their transcriptional profiles to best utilize the new nutrient pool. These changes can manifest as extensive metabolic alterations and lead to 2) changes in microbiome composition, whereby microbes whose niches are best filled increase in abundance. 3) Alternatively or in addition, strain diversification within a species (indicated by the orange microbes) could occur allowing existing microbes to alter their niches and utilize the new compound. This later scenario is reflected in genetic changes to the microbiome. A combination of all scenarios is expected in real microbiomes.

Changes in sugar and sweetener consumption lead to 1) transcriptional, 2) compositional, and/or 3) genetic changes in gut microbes. The colored bar plots represent illustrative fractional compositions of sugars/sweeteners in the gut. 1) In response to a changed set of dietary sugars/sweeteners, microbes can alter their transcriptional profiles to best utilize the new nutrient pool. These changes can manifest as extensive metabolic alterations and lead to 2) changes in microbiome composition, whereby microbes whose niches are best filled increase in abundance. 3) Alternatively or in addition, strain diversification within a species (indicated by the orange microbes) could occur allowing existing microbes to alter their niches and utilize the new compound. This later scenario is reflected in genetic changes to the microbiome. A combination of all scenarios is expected in real microbiomes.

Regarding the first prediction, that microbes can differentially regulate their metabolic networks, the first route available to a microbe for adaptation to an altered nutrient pool is by altering the transcription and protein levels of relevant metabolic and transport proteins. It has been observed that glucose and fructose suppress polysaccharide utilization genes ( 66) by catabolite repression. These sugars suppress the regulatory protein of polysaccharide utilization genes in Bacteroides thetaiotaomicron in the presence of other nonsuppressing sugars and negatively impact the colonization ability of this bacterium in mice ( 66). As well as affecting metabolism inside the bacterial cell, external metabolites present in the gut are also altered by dietary sugar. In mice fed diets where the sole carbohydrate source was either glucose or fructose, the fecal levels of several short-chain fatty acids, amino acids, and sugars differed in the following ways: butyrate and propionate were lower, while succinate, lactate, taurine, tyrosine, threonine, phenylalanine, and xylose were higher in fecal samples from mice fed a fructose diet than in mice fed a glucose diet ( 67).

These transcriptional changes pave the way for the second predictionof global microbiome compositional changes in the gut. While compositional changes in the microbiome due to dietary change have been observed in an abundance of studies, few studies have compared diets that vary only in the presence of a particular sugar. One successful study added 30% fructose (by weight) to the drinking water of mice on either a high-sugar diet (by energy: 26% sucrose, 44% starch, 12% fat, and 18% protein) or a high-sugar/high-fat diet (by energy: 30% sucrose, 13% starch, 42% fat, and 15% protein) ( 68). This addition of fructose altered the microbiome, albeit modestly, in animals on both diets, demonstrating that the addition of a single sugar can impact microbial abundances. Similarly, in rats fed combinations of high-/low-fat (by energy: ∼12% compared with 45%) and high-/low-sucrose (by energy: 3.2% compared with 17%) diets, the animals fed high sucrose, irrespective of fat content, displayed a reduction in fecal microbial diversity and compositional changes in select gut microbes ( 69).

The aforementioned studies concern sugars consumed at the gram level per serving. What of the intense sweeteners that are consumed within the milligram range? Can even lower amounts (tenths or thousandths) of a novel compound introduced to the diet affect the gut microbiome? The work of Suez et al. ( 70), while not without limitations, provides some indication that the answer is yes. In mice fed saccharin at levels expected to be a 5-fold excess from what people actually consume [5 mg/(kg per d) compared with a predicted 1.6 mg/(kg per d)], the abundances of several taxa were altered ( 70). Moreover, saccharin, though not a carbohydrate, appeared to select for microbes with differential gene content for carbohydrate and other macromolecule biosynthesis pathways. While transcriptional changes were not measured, these gene content changes suggest that regulatory events like catabolite repression may be occurring ( 70). It should also be noted that the host was impacted by the saccharin-altered gut microbiota. Germfree recipient mice receiving stools from saccharin-fed animals displayed glucose intolerance similar to that of the donor mice ( 70). These phenotypes could be derived simply by colonizing germfree mice with mouse fecal microbes that had been cultured with saccharin ( 70). The authors were also able to observe similar findings in people. In a cohort of nondiabetic people, several clinical markers indicated worse glucose handling in individuals consuming saccharin than in controls ( 70). As well, these investigators fed saccharin for 1 wk to individuals who did not normally consume saccharin. Some of these individuals (4 of 7) had increased blood glucose concentrations and developed a microbiome that when transferred to germfree animals elevated the blood glucose concentrations of the mice ( 70). While further clinical research is needed in this area, this work suggests that consumption of milligram amounts of a sweetener may induce functional changes in the microbiome and that such changes are dependent on the microbes present.

The third prediction, regarding genetic adaptation and strain emergence, has been more elusive to address. Improved detection methods in strain isolation and metagenomic sequencing have verified that strain variation exists in the human microbiome and within single individuals ( 71–76). However, only recent publications have been able to provide direct evidence for dietary sugars driving strain variation.

Sousa and colleagues were able to demonstrate strain emergence and coexistence with the original bacterial population in response to dietary galactitol, a sugar alcohol derived from galactose. When these investigators inoculated mice with an Escherichia coli strain with a mutation disrupting the ability to make galactitol, part of the E. coli population reverted and regained galactitol metabolism, leading to the coexistence of both galactitol-negative and galactitol-positive strains ( 77). Importantly, the abundances of galactitol-positive E. coli strains in mice co-colonized with both strains were dependent on the amount of galactitol in the mouse diet, while the abundances of galactitol-negative strains were dependent on the total microbiome composition. These findings thus implied that the galactitol-positive strains were able to utilize a poorly exploited galactitol microenvironment, whereas galactitol-negative strains competed with the collective microbiome for other carbon sources.

A similar finding was observed from the paradoxical results of Yin and colleagues. In their study, they tested the survival of Lactobacillus plantarum scrB mutants, incapable of metabolizing sucrose, and their wildtype counterparts ( 78). The strains were singly inoculated into mice fed a high-sucrose diet (by energy: 30% sucrose, 13% starch and maltodextrin, 40% fat, and 17% protein). A day following inoculation, L. plantarum sucrose mutants were cultured from fecal samples at 115% higher levels than wildtype L. plantarum ( 78). These results demonstrate that L. plantarum can shift its metabolic needs to other resources in the gut and, in doing so, it adapts to a less competitive niche. If we use the Restaurant Hypothesis as an analogy, this shift would be akin to L. plantarum deciding between eating in a restaurant with excellent food but booked to capacity or going to a less crowded restaurant with worse food. Given the competition for the first restaurant, the second restaurant is a better choice. Interestingly, the addition of the scrB mutant induced only modest changes in the total gut microbiome. This observation suggests that adaptation to a different sugar source could lead to strain diversification and potentially replacement within a single species without impacting the gut microbiome composition. Such an event would be undetectable if only the microbial community structure was profiled.

Remarkably, these studies demonstrate that diverged strains, originating from the same parental population, can coexist. Coexistence in these cases can be explained by negative–frequency-dependent selection ( 79). As one strain increases in abundance, it depletes the nutrient pool and subsequently reduces the collective fitness of all organisms dependent on that nutrient. This depletion is analogous to a restaurant running out of pie, but still having cake. If some of the patrons diversify to preferring cake, then the restaurant is able to achieve maximal capacity, serving both pie and cake consumers. Similarly, strain diversification in a microenvironment prevents exhaustion of and complete reliance of the local microbial population on one nutrient by shifting at least part of the microbial population to using a different nutrient. As a result, resources are partitioned in the microenvironment and closely related strains coexist.

Evidence supporting multiple and spatially distinct strains was recently found in the human gut. In looking at 602 isolates of Bacteroides fragilis from 30 fecal samples belonging to 12 individuals, Zhao et al. observed variations in genes, including the homologs susC and susD ( 80). These genes are predicted to function in importing polysaccharides, and variation in these genes may reflect a selective pressure on utilization of the host rather than of dietary polysaccharides. Importantly, the evolutionary divergence of coexisting isolates from a single individual suggests niche differentiation. Moreover, the lineages of those isolates remained stable over 1.5 y despite evidence of selective sweeps within the lineages. The authors note that these observations suggest the lineages are spatially separated, in support of our concept of microbial biogeographical identities.

Recently, Collins and colleagues illustrated the possibility of strain selection due to an added dietary sugar occurring in humans ( 81). These authors observed that the hypervirulent RT027 and RT078 Clostridium difficile ribotypes are able to utilize low levels of trehalose effectively through 2 different mechanisms ( 81). RT027 strains contain a mutation in the repressor gene treR, which regulates expression of phosphotrehalase (treA) involved in the catabolism of trehalose-6-phosphate to glucose and glucose-6-phosphate. This mutation results in higher expression of the phosphotrehalase at low trehalose concentrations. RT078 strains, meanwhile, have acquired a second genetic locus that includes homologs of treA and treR, a putative trehalose-specific phosphotransferase system (PTS) system IIBC component transporter gene (ptsT), and a putative glycan debranching enzyme gene. In an in vitro model of C. difficile infection, the RT078 strains with a functional ptsT were able to outcompete strains deleted for this gene. Moreover, the authors were able to demonstrate that the ability of the RT027 strain to utilize low amounts of trehalose increased C. difficile virulence in mice.

While the C. difficile RT027 and RT078 strains existed prior to the introduction of trehalose as a food additive, the emergence of these strains as “hypervirulent” follows the introduction of trehalose in the global food market. This study illustrates a paradigm of microbial adaptation to a modern dietary sugar impacting human health. It should be noted that where selection for these strains first occurred may not have been in humans. The RT078 ribotype is prevalent in livestock, and direct transmission between livestock and humans has been demonstrated ( 82). Consequently, the reservoirs of strain diversity may exist in nonhumans and the environment, while selection occurs in humans.

C. difficile is unlikely to be the only microbe that has undergone selection due to dietary sugars. Over evolutionary history, enterococci host adaptation and speciation is correlated with acquisition of carbohydrate transporters and other utilization genes for dietary sugars ( 83). Moreover, metagenomic data suggest that variation in sugar metabolism is present in many coexisting strains in the gut microbiome ( 72).

Are there other mechanisms by which dietary sugars and sweeteners can affect gut microbes?

So far, we have limited our discussion on the effects of dietary sugars/sweeteners to their roles as nutrients for the microbiome. It must be considered, however, that some of these compounds may inhibit or be toxic to the gut microbiome. Indeed, for several dietary sugars and sweeteners, this situation has been demonstrated to be the case. Xylitol was introduced to foods for this very functionality. In the 1970s, it was observed that oral bacteria are unable to utilize, grow, or adapt to xylitol ( 84, 85), and hence xylitol is frequently added to oral products and gums. Similarly, some strains of Lactobacillus reuteri are growth inhibited by stevia glycosides ( 86) and sucralose inhibits growth and activates heat stress, DNA damage, and membrane damage responsive promoters in E. coli ( 87). Nevertheless, it must be kept in mind that these sugars and sweeteners are not universally toxic and microbes capable of metabolizing these compounds exist ( 88, 89).

While it is straightforward to hypothesize that the effects of dietary sugars and sweeteners on gut microbes are solely direct, it would be naïve to ignore concurrent changes in the host environment. Thaiss et al. observed that when at least 8 g/L (44 mM) glucose is applied to Caco-2 cells, the cell–cell junctions become more curvy and sinuous after at least 24 hours ( 90). These changes are hypothesized to cause the reduced mucus thickness and impaired barrier integrity observed under hyperglycemia, which in turn leads to endotoxin translocation, an immune response, and alterations in the gut microbiome ( 68, 90). It should be noted, however, that luminal concentrations of glucose in the small intestine are not regularly this high. Glucose concentrations of 25–100 mM can be observed in rats consuming a 67% by energy glucose diet, but these concentrations are only observed in the upper small intestine and for <8 h ( 91). Normal concentrations of glucose in the mammalian small intestine range from 0.2 to 48 mM ( 91). Additionally, hyperglycemia is defined as a fasting blood glucose concentration >11 mM ( 92). Therefore, the specific cellular effects of glucose on intestinal cells leading to loss of barrier integrity need to be further investigated.

What pathways could be affected in adapted microbes and how might these adaptations affect the host?

One way to conceptualize the microbial and host processes affected by microbial adaptation is to follow the sugar/sweetener from the gut lumen to inside the microbe and back out ( Figure 4). The first line of interaction between microbes and a dietary sugar/sweetener is typically an import system. These include phosphotransferase systems (phosphate dependent), major facilitator superfamily transporters (ion coupled), ATP-binding cassette transporters (ATP dependent), sodium–glucose linked transporters (Na + coupled), and glucose uptake transporters (facilitated diffusion) ( 93). The type of transport system varies by microbe and type of sugar ( 93). As well, some sugars are imported by multiple transport systems in a given organism ( 93–95). Following import, the sugar/sweetener enters into metabolic pathways. An example of selection acting on these processes in microbes was observed in E. coli. E. coliadapted in vitro to sucrose display mutations in or affecting the regulation of sucrose transport (a permease) and metabolism (a fructokinase and a sucrose hydrolase) ( 96). Furthermore, in metagenomic studies of mice fed a high-sugar/high-fat diet (by energy: 16–30% sucrose, 10–25% starch and maltodextrin, 40–45% fat, 15–19% protein), genes involved in sugar transport and metabolism were enriched ( 15, 22).

Host effects resulting from microbial adaptation to dietary sugars. Microbial adaptation to sugar is observed in sugar transporters and metabolic genes and produces changes in microbial proliferation and behaviors. These changes also lead to differential microbial primary and secondary metabolites including polysaccharides and monosaccharides, short chain fatty acids, and toxins. Secondary metabolites including toxins can lead to destruction of the epithelium and subsequent sepsis. Polysaccharides and monosaccharides, short chain fatty acids, and other sweetener metabolites can be absorbed, metabolized, and taken up into host circulation via G protein–coupled, SGLT, GLUT, and other cell surface transporters. Polysaccharides and monosaccharides can also become incorporated into extracellular glycoconjugates, including lipopolysaccharides, exopolysaccharides, capsular polysaccharides, biofilms, and flagella. These structures are recognized by the host immune system through toll-like receptors, C-type lectins, immunoglobins, and other molecules. Recognition can lead to an anti-inflammatory or proinflammatory response. Specific glycoconjugates can block this recognition, allowing the microbe to evade the immune system. These structures also permit attachment to the host epithelium. ABC, ATP-binding cassette GLUT, glucose transporter SGLT, sodium–glucose cotransporter TCA, tricarboxylic acid cycle.

Host effects resulting from microbial adaptation to dietary sugars. Microbial adaptation to sugar is observed in sugar transporters and metabolic genes and produces changes in microbial proliferation and behaviors. These changes also lead to differential microbial primary and secondary metabolites including polysaccharides and monosaccharides, short chain fatty acids, and toxins. Secondary metabolites including toxins can lead to destruction of the epithelium and subsequent sepsis. Polysaccharides and monosaccharides, short chain fatty acids, and other sweetener metabolites can be absorbed, metabolized, and taken up into host circulation via G protein–coupled, SGLT, GLUT, and other cell surface transporters. Polysaccharides and monosaccharides can also become incorporated into extracellular glycoconjugates, including lipopolysaccharides, exopolysaccharides, capsular polysaccharides, biofilms, and flagella. These structures are recognized by the host immune system through toll-like receptors, C-type lectins, immunoglobins, and other molecules. Recognition can lead to an anti-inflammatory or proinflammatory response. Specific glycoconjugates can block this recognition, allowing the microbe to evade the immune system. These structures also permit attachment to the host epithelium. ABC, ATP-binding cassette GLUT, glucose transporter SGLT, sodium–glucose cotransporter TCA, tricarboxylic acid cycle.

Whether changes in microbial sugar/sweetener transport and metabolism directly affect the host is uncertain. These changes, however, are associated with effects on the host. In several different human populations, increases in microbial gene content for sugar metabolism and transport are associated with type 2 diabetes and obesity ( 97–99). Similar microbial metabolic profiles were enriched in the previously mentioned study by Suez and colleagues, in which saccharin promoted a glucose intolerance promoting microbiome ( 70). As previously mentioned, comprehensive clinical studies coupled with microbiome analyses using nutritionally relevant amounts of saccharin or other specific sugars/sweeteners need to be performed to fully address this question.

Continuing inside and back out of the microbial cell, dietary sugars are incorporated into glycoconjugates, including peptidoglycans, capsular polysaccharides, exopolysaccharides, and lipopolysaccharides, in the cell wall and membrane ( 100). These glycoconjugates serve a variety of functional roles for microbes, including strain identification among microbes and by the host ( 101). For example, DC-SIGN (dendritic cell–specific intercellular adhesion molecule-3–grabbing non-integrin) lectins ( 100) and immunoglobulin A ( 101) actively promote colonization of microbes in the gut by recognizing displayed microbial glycoconjugates. Specific exopolysaccharides can promote interleukin-10–mediated anti-inflammatory immune responses ( 65). On the other hand, lipopolysaccharide stimulates a proinflammatory immune response through toll-like receptor (TLR) 4 (TLR4) signaling ( 102) and is associated with metabolic syndrome ( 103). Therefore, microbial sugar adaptation can significantly affect host–microbe interactions as well as determine whether the immune system actively removes, promotes, or ignores a microbe.

Available sugars also impact the formation of biofilms ( 104, 105), flagellar structures ( 100), and motility ( 106). Biofilms and flagella can alter microbial persistence in the gut, interact with the immune system, and have strong impacts on host disease states. In particular, biofilms have been implicated in colorectal cancer ( 107) and antibiotic resistance ( 108). While flagella normally stimulate the immune system through TLR5, there is some evidence suggesting that glycosylation of flagella reduces TLR5 recognition in the opportunistic pathogen Burkholderia cenocepacia ( 109) and enhances C. difficile adhesion to epithelial cells ( 110).

Moving further outside the cell, microbial metabolites can be formed from sugar/sweetener metabolism. For example, microbially produced short-chain fatty acids may link microbial carbohydrate metabolism and host obesity by providing an additional energy source to the host ( 111) or by activating anti-inflammatory pathways ( 103). Microbially produced lactate has also been demonstrated to stimulate intestinal stem cell proliferation and epithelial cell development, thereby protecting the small intestine against chemical- and radiation-induced injury ( 112). Stevia is broken down by microbes to steviol, which is processed in the liver and converted to steviol glucuronide ( 113) this process is not known to cause any effects on the host. Other links between dietary sugars/sweeteners and microbial metabolites remain to be understood. For example as mentioned earlier, C. difficile adaptation to trehalose is linked to increased toxin production in mice consuming trehalose ( 81).

Finally, there are likely many other mechanisms by which microbial interactions with sugars and sweeteners impact the host. There is evidence in humans and in animal models that sugar alcohols promote several beneficial microbes ( 114, 115). Whether this interaction occurs simply by promoting the growth of these microbes or through a more complex interaction is unknown. A new finding indicates that fructose increases phage production in L. reuteri through a stress–response pathway and thus alters microbiome composition in a novel manner ( 116). As mentioned earlier, the transport and metabolic genes involved in sugar metabolism are regulated by the presence of other sugars, leading to preferential metabolism of one sugar over another ( 117). Thus, in systems where multiple sugars are present, the effect of adding a novel sugar to a system may not directly impact the genes involved in transporting and metabolizing that sugar or may only affect a subpopulation of cells ( 48), potentiating strain diversification.

What approaches can be used for studying microbial adaptation to human sugar and sweetener consumption?

How do we move forward in trying to understand mechanistically how dietary sugars and sweeteners reshape the gut microbiome and affect host physiology? Research needs to identify not only the sugars that can be used by microbes, but also what metabolites and biological processes are affected by a given sugar, how microbes can adapt to altered carbohydrate pools, the existing variation in sugar metabolism within the human microbiome, and the effect of such adaptation and variation on human physiology. Here we discuss the use of experimental evolution, organoids, and host genetic background to address these topics.

Experimental evolution is a powerful and underutilized technique to explore the adaptive capability of microbes to a novel nutrient pool. To model the gut, various culture systems (bioreactors, fermenters, and chemostats) have been developed with varying levels of complexity, ease of use, and scalability ( 118–123). Experimental evolution can be accomplished in live hosts as well, by passaging communities from host to host. This is best achieved using gnotobiotic animals where the microbial community can be controlled ( 124, 125). Evolved microbes and their metabolites can be tested for their interaction in hosts or in cell culture models (see below).

Gut organoids are an advanced cell culture methodology that allows for determination of events that occur at the epithelial layer of any region of the gut ( 126). While still more simplified than a complete host, variations on these systems allow for magnification of gut events. For example, enteroendocrine-cell–enriched enteroids allow for the ability to detect changes in gut hormones due to a microbial metabolite ( 127, 128). As well, these systems can be used to study how changes in a microbe's physiology changes its adhesion to gut cells ( 129) or other host–microbe interactions.

Analysis of the microbiomes of individuals avoiding particular sugars because of health preferences or as restricted by a genetic condition is a viable method to provide insight into how dietary sugar shapes the human microbiome. In the latter case, strong mechanistic support was provided for the positive correlation between Bifidobacteria and lactose through the finding that individuals who do not produce lactase in adulthood have higher levels of Bifidobacteria ( 130, 131), implying that individuals not producing lactase, yet still consuming lactose, have more free lactose available to the gut microbiome, which promotes the growth of lactose-utilizing Bifidobacteria.

Similar observations may be true for individuals with other metabolic deficiencies. Individuals with mutations in SLC5A1 are unable to transport glucose and galactose via SGLT1 ( 132, 133). These individuals experience life-threatening diarrhea on consumption of lactose, glucose, and galactose, but not fructose. However, certain individuals gain tolerance to these sugars as they age ( 134), perhaps through adaptations of the microbiome. Fructose intolerance ( 135) has been traced to a lack of aldolase B, fructokinase, or FBPase ( 136), deficiencies in the fructose transporter GLUT8, or simply by overloading the transporter GLUT5 ( 137, 138). These individuals suffer from irritable bowel syndrome symptoms and/or hypoglycemia. Removal from their diet of fructose and other sugars sharing the same pathways/enzymes improves their condition ( 136, 138, 139). Trehalase deficiency has been documented in Finnish individuals, causing affected individuals to suffer from abdominal pain on consuming trehalose ( 140). At least 8% of Greenland's population is reported to have trehalase deficiency via autosomal dominant inheritance ( 141). These groups of people represent rare opportunities to assess in humans the lifelong effects on the microbiome of the absence or reduction of a single sugar.


Can more fiber restore microbiome diversity?

Scientists are pushing to restore human health in Western countries by changing our diet to restore the microbial species lost over the evolution of Western diet. In a Commentary published April 11 in Trends in Endocrinology & Metabolism, researchers at the University of Alberta advocate for strategically increasing dietary fiber intake as one path forward in regaining microbial biodiversity.

Insufficient nutrients for our gut microbes have been linked to a loss of certain beneficial bacterial species in industrialized societies and are likely impacting our immunological and metabolic health, although more data is needed. For example, most Westerners consume half of the amount of dietary fiber recommended by dietary guidelines, which nutritionists refer to as the "fiber gap," which is a problem because dietary fiber is the primary source of nutrition (e.g., carbohydrates) accessible to gut bacteria in humans.

"The idea to boost fiber levels is not new," says Jens Walter of the University of Alberta, Canada. "However, depletion of the microbiome adds a new perspective to this low-fiber Western diet that we are currently eating."

Earlier this year, Stanford University's Justin Sonnenburg found that mice fed a typical Western diet (high in fat and carbohydrates and low in fiber) transferred a lower diversity of beneficial microbial species to future generations. The re-introduction of the microbes' preferred fiber at that stage did not result in a return of some (good) species, indicating that extinctions had occurred in only a few generations.

Walter and co-author Edward Deehan, his PhD student, are concerned that a dramatic shift away from a diet similar to the one under which the human-microbiome symbiosis evolved is a key factor in the rise of non-communicable disorders like obesity.

"There is a lot of epidemiological evidence that fiber is beneficial, and food products containing dietary fiber have FDA-approved health claims for both colon cancer and coronary heart disease. There is also quite a bit of clinical evidence (although it is less consistent)," Walter says. "The most pressing issue at the moment that neither consumption of fiber in society nor the doses used in clinical research are high enough."

Walter has noticed that often researchers evaluating fiber doses in diets and health outcomes do so with "doses of fiber that [he] would consider physiologically irrelevant. Most of these studies use 5-15 grams of fiber I would not think that these amounts would be actually beneficial," he says.

People living in non-industrialized societies have an average intake of fiber that is much higher than the low norms of Western societies. The authors note the recent work from the Stephen J.D. O'Keefe lab in Nature Communications (doi:10.1038/ncomms7342) in which modern African-Americans were given a traditional South-African diet that contained 55 grams of daily dietary fiber and had improved markers for colon cancer within two weeks.

In their Commentary, the authors propose a concerted effort by scientists, food producers, policy makers, and regulatory groups to address the fiber gap. They emphasize that clinical assessments of different fiber types and fiber-enriched foods on microbiome outcomes are needed.

Jens Walter also asserts that the challenge of restoring diverse gut inhabitants will be best met with regulatory policies that are specific to food, and not just the same as those for drugs. "To have a regulatory environment that makes it extremely hard to obtain health claims for food substances is very detrimental," says Walter. He is hopeful that regulatory policies will change to encourage innovative research on disease prevention by modulating the diverse microbial communities humans have evolved with and the ways our diet shapes them and by extension, all of us.


About Our Study

Why are you conducting this study?

This study will examine changes to the composition of the microbiome that occur in response to eating or avoiding dairy products, and the time course of such changes. We hypothesize that certain bacterial species in the gut microbiome are associated with acquired lactose tolerance: they allow hosts to eat dairy products without suffering the negative outcomes characteristic of lactose intolerance. We further hypothesize that regularly eating dairy products is necessary for the persistence of a lactose tolerance in most individuals, with dairy acting as a prebiotic to support the populations of lactose-utilizing, tolerance-associated bacteria. If these hypotheses are correct, our study may support informed consumption of dairy products in lactose intolerant individuals it would allow them to develop and maintain lactose tolerance and to reap the potential health benefits of dairy, e.g. those related to the uptake of calcium.

What will the study entail?

The study will last three months and involve three main phases: a normal diet consumption phase, no dairy consumption phase, and a gradual reintroduction to dairy phase. During the study, participants will complete four hydrogen breath tests (which entail 4-6 hours of blowing into a tube every 20 minutes at home and doing whatever you like in between) and take their own stool samples regularly (preferably daily).

The study is looking for participants who at some point (past or present) have experienced symptoms such as cramping, bloating, and diarrhea when eating dairy. The study is also looking for participants who will not be travelling during the course of the study.

Why should I participate?

The main reason for people to participate is because they want to help this science to move forward, whether that's so medical science can do a better job of keeping people healthy, or just because it's fascinating!

Another reason would be to learn about your own gut microbiota. Once your samples have been analyzed (which can take a while), you can choose to meet with one of the study staff to find out what we've learned about your own microbes. We'll also discuss how your results compare to those from other people, and how they relate to other published scientific studies. You should know, though, that scientists don't yet know enough to provide specific health or medical advice to generally healthy people based on knowledge of their microbiota. The best advice we can give for you and your microbiota is to eat a balanced, healthy diet - and that advice doesn't depend on knowing what microbes are in your gut already!

The compensation will be $400 per participant but please don't sign up if that's your only motivation.

What now?
To find out more and check your eligibility click this link.


Diet and gut microbes affect cancer treatment outcomes

What we eat can affect the outcome of chemotherapy - and likely many other medical treatments - because of ripple effects that begin in our gut, new research published in Nature Communications suggests.

University of Virginia scientists found that diet can cause microbes in the gut to trigger changes in the host's response to a chemotherapy drug.

Common components of our daily diets (for example, amino acids) could either increase or decrease both the effectiveness and toxicity of the drugs used for cancer treatment, the researchers found.

The discovery opens an important new avenue of medical research and could have major implications for predicting the right dose and better controlling the side effects of chemotherapy, the researchers report.

The finding also may help explain differences seen in patient responses to chemotherapy that have baffled doctors until now.

"The first time we observed that changing the microbe or adding a single amino acid to the diet could transform an innocuous dose of the drug into a highly toxic one, we couldn't believe our eyes," said Eyleen O'Rourke, PhD, of UVA's College of Arts & Sciences, the School of Medicine's Department of Cell Biology and the Robert M. Berne Cardiovascular Research Center. "Understanding, with molecular resolution, what was going on took sieving through hundreds of microbe and host genes. The answer was an astonishingly complex network of interactions between diet, microbe, drug and host."

How diet affects chemotherapy

Doctors have long appreciated the importance of nutrition on human health.

But the new discovery highlights how what we eat affects not just us but the microorganisms within us.

The changes that diet triggers on the microorganisms can increase the toxicity of a chemotherapeutic drug up to 100-fold, the researchers found using the new lab model they created with roundworms.

"The same dose of the drug that does nothing on the control diet kills the [roundworm] if a milligram of the amino acid serine is added to the diet," said Wenfan Ke, a graduate student and lead author of a new scientific paper outlining the findings.

Further, different diet and microbe combinations change how the host responds to chemotherapy.

"The data show that single dietary changes can shift the microbe's metabolism and, consequently, change or even revert the host response to a drug," the researchers report.

In short, this means that we eat not just for ourselves but for the more than 1,000 species of microorganisms that live inside each of us, and that how we feed these bugs has a profound effect on our health and the response to medical treatment.

One day, doctors may give patients not just prescriptions but detailed dietary guidelines and personally formulated microbe cocktails to help them reach the best outcome.

Researchers have observed microbes and diet affecting treatment outcomes before.

However, the new research stands out because it is the first time that the underlying molecular processes have been fully dissected.

A new model

The researchers' new model is an extremely simplified version of the complex microbiome - collection of microorganisms - found in people.

Roundworms serve as the host, and non-pathogenic E. coli bacteria represent the microbes in the gut.

In people, the relationships among diet, microorganisms and host is vastly more complex, and understanding this will be a major task for scientists going forward.

The research team noted that drug developers will need to take steps to account for the effect of diet and microbes during their lab work.

For example, they will need to factor in whether diet could cause the microorganisms to produce substances, called metabolites, that could interfere or facilitate the effect of the drugs.

The researchers suggest that the complexity of the interactions among drug, host and microbiome is likely "astronomical."

Much more study is needed, but the resulting understanding, they say, will help doctors "realise the full therapeutic potential of the microbiota."

"The potential of developing drugs that can improve treatment outcomes by modulating the microbes that live in our gut is enormous," O'Rourke said. "However, the complexity of the interactions between diet, microbes, therapeutics and the host that we uncovered in this study is humbling. We will need lots of basic research, including sophisticated computer modelling, to reveal how to fully exploit the therapeutic potential of our microbes."


How Your Gut Bacteria Can Help You Lose Weight

It&rsquos time to bug out. Bacteria in your gut may be the secret to finally losing weight.

What if you could enjoy a chocolate bar without taking in all its calories? This isn&apost just wishful thinking. It may already be happening, thanks to the trillions of microbes in your digestive system.

Until recently, the assumption was that the bacteria huddling in your intestine pretty much mind their own business. But now a growing body of research suggests that your internal community of bacteria, known as a microbiota, could be influencing your metabolism and, surprisingly, affecting your weight. Turns out, the gut bacteria-weight-loss connection is a pretty fascinating one. (Here&aposs what you should be eating for a healthy gut.)

What Scientists Know About Gut Bacteria and Weight Loss

For example, having a greater abundance of a recently discovered type of bacteria called Christensenellaceae in your gut is associated with being slim, while having less of the bacteria is linked to being obese, a study in the journal Cell shows. "How much you have is partially determined by genetics," says lead study author Julia Goodrich, a graduate student at Cornell University. The good news is that most of us harbor the bacteria—it was detected in 96 percent of the study samples𠅊nd it may be possible to alter our levels of gut bacteria for weight loss.

Christensenellaceae isn&apost the only gut bacteria that might affect weight loss. A diverse mixture of microbes in the gut seems to be one key to staying slim, says Jeffrey Gordon, M.D., the director of the Center for Genome Sciences and Systems Biology at the Washington University School of Medicine, who was one of the first researchers to link intestinal bacteria and obesity. In fact, research found that lean people have 70 percent more gut bacteria and therefore a more diverse microbiota than that of their overweight peers. Other findings have found that people in the United States, who have a high rate of obesity, have less-diverse gut microbes than people from less developed parts of the world do. The correlation is consistent enough that in a study of twins, "we could predict whether one was lean or obese based solely on their gut microbes," says Rob Knight, Ph.D., a cofounder of the American Gut Project. (Related: Nutritious Juice Shots for Gut Health)

The impact of the gut bacteria-weight loss link isn&apost known yet, but many researchers believe that your gut microbiota plays a role in processing food and helping to determine how many calories and nutrients your body absorbs. Certain intestinal microbes may also alter your sensitivity to insulin—the hormone that moves sugar out of your blood—so that your body burns fat it would have otherwise stored. Interestingly, it only takes a few days of eating high-fat foods to disturb the balance of good and bad bacteria in the gut, which throws off an important process of breaking down undigested macros.

Your gut bacteria might affect how hungry you are too. One key microbe appears to be Helicobacter pylori, the bacterium that&aposs involved in causing ulcers and stomach cancer. Antibiotic treatments have helped cut H. pylori infection rates in half in recent decades, which is good news for ulcer sufferers-but which could be bad news for our waistlines. H. pylori also dials back the stomach&aposs production of the hunger hormone ghrelin. "When you wake up in the morning and you&aposre hungry, it&aposs because ghrelin is telling you to eat," says Martin Blaser, M.D., a professor of medicine and microbiology at New York University and the author of the book Missing Microbes. "When you eat breakfast, your level of ghrelin usually goes down, but if you don&apost have Helicobacter in your system, it doesn&apost." The end result: You could eat more. (Related: 8 Tips to Absorb More Nutrients From Your Food)

The Impact of Antibiotics on Gut Bacteria and Weight Loss

You might not even have to take antibiotics to feel their effects on your gut bacteria. The heavy reliance on antibiotics by the food industry, which routinely uses the drugs in feed to keep livestock healthy, may be fueling the rise of obesity by disrupting the fine balance of our intestinal microbes, some experts believe. "The obesity epidemic really took off in the last 20 years in the U.S. So the question is, what happened then? What was a large segment of the population exposed to that could account for this massive weight gain?" asks Lee Riley, M.D., a professor of epidemiology at the University of California, Berkeley. He points out that that&aposs when the number of large-scale densely packed factory farms expanded, which also increased the use of antibiotics in livestock feed. Today, 80 percent of the antibiotics sold in the United States go toward helping animals remain healthy and gain more weight in crowded conditions. "Counties with the highest prevalence of obesity are those counties with large concentrated animal feeding operations," he says.

Not to mention that antibiotics are often used when they shouldn&apost be, as when doctors prescribe them for viral infections or because patients demand them. (Sometimes a full course of antibiotics isn&apost necessary.) The exact repercussion on human health is still being debated, but Dr. Blaser says that the gut bacteria-weight loss link in laboratory studies is pretty clear. "If you put mice on a high-fat diet, they get fat," he says. "If you put them on antibiotics, they get fat. And if you put them on both, they get very fat."

While some of your gut bacteria is determined by genetics, life­style and dietary habits can have a dramatic impact on your mix of beneficial and harmful microbes. A study in the journal Nature found that when people switched from their normal diet to one consisting primarily of meat and cheese, there was an almost immediate increase in Bilophila, a type of bacteria that has been linked to colitis, but that a plant-based diet decreased the levels.

4 Ways to Keep Your Gut Bacteria Healthy

Eat more fiber. It&aposs the number-one thing you can do to better your gut bacteria (and hopefully help with weight loss), says Justin Sonnenburg, Ph.D., an assistant professor of microbiology and immunology at Stanford University. Research suggests that fiber nourishes your microbes, making them diverse and more likely to help keep you at a healthy weight. Avoid the temptation to buy processed foods that have added fiber. Instead, eat vegetables, fruits, and whole grains. Aim for at least two to three servings each of produce and whole grains and 20 to 30 grams of fiber a day, says Mark Moyad, M.D., a urologist and the author of The Supplement Handbook. These foods also provide prebiotics, which are essentially a type of fiber that your gut bacteria flourishes on. Some plants, like sunchokes, garlic, and leeks, are packed with prebiotics. Bananas and whole-wheat breakfast cereals are other good sources. (Related: This Study About Fiber-Rich Carbs Might Make You Rethink the Keto Diet)

Snack smarter. The fact that we consume so much added sugar—more than 22 teaspoons a day for the average person𠅌ould actually be starving our gut flora, says Sonnenburg. Bacteria need complex carbohydrates, like legumes and whole grains, in order to thrive. So when you get too many calories from sweets, you&aposre leaving your microbes hungry. They either die or adapt by feeding on the mucus inside your intestine, which, experts hypothesize, could contribute to low-level inflammation, a condition that has been linked to obesity. Instead of grabbing a cookie when your stomach starts growling at 3:00 p.m., reach for a handful of nuts or an apple. Check labels for hidden sugars in foods like pasta sauce and salad dressing. And choose brown rice and whole-grain pasta instead of white.

Pick probiotic foods. If prebiotics are like fertilizer for your microbial garden, probiotics are like seeds. The best way to get them is by regularly eating fermented foods such as yogurt, kefir, sauerkraut, and miso. And about yogurt, that probiotic rock star: A landmark study in the New England Journal of Medicine reported that among all foods studied, yogurt was the one most strongly correlated with weight loss. The average person gained almost a pound a year, but people who regularly ate yogurt actually lost weight. Choose plain Greek yogurt and mix in pomegranate seeds or your favorite berries for a hit of fiber. (Related: 5 Legit Benefits of Probiotics)

Move your body. Your bacteria might benefit from a good workout as much as you do. Exercisers with a normal BMI had more diverse microbes than exercisers with a high BMI, according to an Irish study of male rugby players. They also had higher levels of Akkermansiaceae, a type of bacteria that has been linked to lower obesity rates. So sweat daily to trim your gut𠅊nd to boost your gut bacteria.