A growing body of evidence accumulated by studies of gut microbiota in world populations emphasizes that lifestyle and especially diet strongly impact microbiota composition and, thus, human health. However, it is still unclear how durable are the effects of dietary changes, either long- or short-term. Effects of self-administered short-term dieting efforts on gut microbiota are also far from being well understood. To investigate this problem, we used an Internet-based citizen science-supportive platform to enroll individuals from the Russian urban population into the study aimed at identifying the links between gut metagenome composition and long-term dietary habits, assessed using a food frequency and lifestyle questionnaire and short-term dietary changes achieved during a 2-week intervention.
One of the major observations derived from the analysis of microbiota composition and the recent medical history of the subjects was an influence exerted on gut community by recent intake of antibiotics. No detailed breakdown of antimicrobial drugs was available. The diversity of the antibiotics modes of action might explain the lack of consistency in observations concerning individual microbial taxa. However, on the level of cooperatives, or symbiotic groups of microbes, a significant depletion of the Ruminococcaceae
-dominant cooperative was detected in the gut of the participants recently exposed to antibiotics. Interestingly, many drivers of this antibiotic-sensitive cooperative, in particular Methanobrevibacter
, were previously linked to leanness. These bacterial generally also manifest high heritability [47
]. Another member of this cooperative, Oscillibacter
, is associated with normal BMI [56
]. Moreover, many microbes from this cooperative, including Ruminococcaceae
, are known to degrade complex dietary fibers, resulting in the production of butyrate [57
], an anti-inflammatory compound that also plays essential roles in the regulation of metabolism, glucose tolerance, and gut motility [58
]. These observations support our findings that the abundance of the Ruminococcaceae
-dominant cooperative correlates with the long-term trends in the consumption of fruit and vegetables.
The idea that antibiotics-driven disruption of the ability of microbiota to support host metabolism contributes to the risk of metabolic diseases, especially in the younger ages, has been discussed before [59
]. It is tempting to speculate that antibiotics might interfere with the host metabolism, through the depletion of beneficial microbial taxa with slow recovery rates and high heritability. In turn, the loss of these specialists would render the host less responsive to the microbiota-mediated effects of high-fiber diet interventions, and, therefore, less likely to return back to the original, “healthier” state.
Out of all long-term diet features, fiber content was the most prominently associated with microbiota composition. The list of microbes correlated with the consumption of fruit, vegetables, and grains included taxa actively involved in the degradation of non-digestible polysaccharides, in particular, species belonging to Oscillibacter
] and ones related to Clostridium clariflavum
]. On the other hand, the consumption of meat products was inversely correlated with the abundance of unclassified species from Prevotella
, a genus linked to diets low in animal protein and high in fiber [65
]. Subjects who consumed more dairy products had higher levels of Streptococcus
in their microbiota, possibly because S. thermophilus
, a major component of starter cultures for fermented milk products, is capable of survival in the human gut [67
Gender was the only anthropometric factor significantly associated with microbiota composition (Figure S3
-dominant cooperative was increased in the gut of female participants. This agrees with the previous observations that harder stools are more common in women, and that harder stools have higher fraction of Bacteroides
than loose samples [68
In our study, the dietary change recommendations were quite general, with predominant targeting of the fiber consumption, and an adherence to the recommendations was uncontrolled. Nevertheless, paired comparison of gut metagenomes before and after the 2-week diet intervention detected substantial changes in the structure of the gut community. In voluntary dieters, the magnitude of observed change was about two times higher than that in subjects who did not change their diet, and several times higher than the technical variation introduced at the stages of DNA extraction, sample collection, and library preparation (Figure S7
While some of the identified short-term changes in the microbial landscape resembled the impacts of long-term high-fiber diet, others were specific and novel. In particular, there was a significant decrease of the Bacteroides
-dominant cooperative as well as of many of its members, including Bacteroides
and in the related Bacteroidaceae
families. Many microbes from these taxa are either bile-tolerant or previously positively associated with long- or short-term diets rich in animal protein and saturated fats [11
]. Apparently, due to intervention-related increase of the fiber intake and, possibly, to partial replacement of animal products with the fiber-containing ones, these bacteria yielded to those specializing in a variety of complex polysaccharides. The microbes that increased after the diet included those associated with a healthy gut to include Clostridiaceae
, particularly, Clostridium
genus, previously linked to high-fiber diet [71
were reported to be inversely correlated with BMI [48
] and Lachnospiraceae
-dominant cooperative was enriched with butyrate producers (Dorea
). Interestingly, we also observed a decrease of Prevotellaceae
(on the genus level—of Prevotella
) associated with the long-term consumption of high-fiber diet.
Changes at the microbial taxa level were mirrored by transitions between permatypes (Figure 4
C). After the diet, many subjects originally belonging to Permatypes 1 and 2 moved to Permatype 3, while a majority of Permatype 3 subjects maintained their permatype. Having a Permatype 3 was associated with higher consumption of vegetables, higher diversity of diet, and high prevalence of butyrate-producing Firmicutes
. Overall, we conclude that even a brief high-fiber diet intervention may produce profound effects resembling those typically associated with long-term dietary changes beneficial to human health.
Interestingly, a slight but significant decrease of gut community diversity after the short-term diet was observed. This effect of the short-term high-fiber diet appears to be opposite to the correlation between diversity and long-term vegetable consumption clearly seen in our cohort. Other studies linked lower alpha-diversity to immune and metabolic disorders as well as to antibiotic intake [72
]. On the other hand, there is evidence to suggest that two weeks of a high-fiber diet may not be enough to affect alpha-diversity [11
]. A slight drop in alpha-diversity obtained in the current study may reflect the “shock effects” of a relatively rapid change in the spectrum of incoming nutrients, which may transiently disrupt the ecology of the gut community. Another observed facet of microbiota “stress” linked to the transitory period is the slightly but significantly increased abundance of Staphylococcus
. Apparently, while the beneficial microbes associated with high-fiber already started to win their niches and extend their presence in two weeks, the disturbance of the ecological network led to the rise of pathobiont and auxotrophic taxa [30
The extent to which gut microbiota reacts to diet interventions was shown to vary across individuals, thus confirming previous observations [74
]. In our study, the degree of response was dependent on initial microbiota composition, but neither on any personalized recommendations nor on any long-term factor revealed by the questionnaire. In the “responders”, a higher abundance of Bacteroidales
and lower abundance of Coriobacteriales
was noted at the baseline. Interestingly, bacteria that increased after dieting generally corresponded to the set of taxa underrepresented at the baseline, with a subsequent decrease of the Bacteroidetes
ratio. Our finding closely resembles observations reported for a Danish cohort of obese and non-obese subjects exposed to a weight-loss diet [75
]: the microbiota of “responders” was dominated by Bacteroides
, while “non-responders” had increased proportions of Blautia
In “responders”, the microbes overrepresented at the baseline, including Bacteroidaceae
, became underrepresented after the diet (Figures S12 and S13
), while underrepresented microbes, including Coriobacteriaceae
, became overrepresented (Figures S12 and S13
). This “responders”-specific correctional “overshoot” led to a pronounced lowering of the Bacteroidetes
ratio (Figure 3
B,C) after the diet. This observation may reflect a momentum-like property of gut community structure dynamics in the landscape of possible configurations during a high-fiber diet intervention (Figure 5
). The Bacteroidetes
-rich microbiota of “responders” appears to reside in a less stable state than the Firmicutes
-rich microbiota of “non-responders”, thus making the “responder” more amenable to change. On the contrary, the microbiota of “non-responders” changed slightly upon intervention because of its higher stability. When the microbiota composition of “responders” gains momentum, it moves towards the “non-responders” and even further to reach a state of lower Bacteroidetes
ratio, normally not accessible to “non-responders”. Whether this acquired community structure remained unstable (marked by A in the Figure 5
) or stable (marked by B) is still to be determined. It is also intriguing to examine if other nutritional changes or other types of interventions would result in alternate dynamics and hence alternate stability landscapes.
Although in the present study the dietary recommendations were personalized, ultimately at their core was an advice to consume more high-fiber products. Our observations suggest that a high-fiber diet is expected to produce more pronounced changes in the microbiota of subjects who initially hosted a higher fraction of Bacteroides. While this fact could be used to stratify populations before assigning such an intervention, the current results do not allow us to infer directly neither the changes in various microbiota types that will occur after the consumption of specific food products nor their implications for human health. However, our study is one of the first steps towards developing a precision microbiota-tailored personalized diet. It emphasizes that in microbiota surveys of dietary interventions it is important to analyze the interindividual response variability—particularly, to facilitate future meta-analysis. We anticipate further studies on large-scale cohorts from diverse geographic locations who consume specific dietary interventions (preferably, based on the introduction of a single product per study) that will identify responders to these pointwise interventions and further utilize these as a basis to design individual dietary plans. Another important question is related to the concept of response itself. In our study, we assessed it as an overall extent of change in the gut community structure. However, in future studies it can be improved by focusing on the increase of species associated with health, alpha-diversity and/or microbiota resilience—as well as by combining with the physiological parameters of a subject.
Overall, this study expands the current understanding of the extent of the changes in microbiota composition caused by short-term dieting. Advancing a microbiota-targeted diet as a novel modality to be developed in the frame of personalized medicine requires the emergence of early adopters eager to participate in a new trend at the crossroads of translational medicine and citizen science. In this cohort, even a brief, uncontrolled high-fiber diet intervention produced considerable beneficial changes in microbiota. Nevertheless, the observed “shock” effects, although slight, suggest that the duration of microbiota-targeted interventions should be longer than two weeks.