Gut microbiota, diet, and metabolic diseases: a triangular relationship

Authors

Abstract

Current evidence highlights the importance of the gut microbiota in connecting the metabolic responses of dietary interventions. A scoping review system- atically mapped and synthesized the evidence from 49 randomized controlled trials (RCTs) on the mediating effect of changes in gut microbiota. Databases were searched for RCTs involving adult participants that reported on both gut microbiota and metabolic outcomes. Eligible studies included defined dietary interventions. Interventions were found to alter microbiome diversity reliably and boost the prevalence of beneficial organisms (such as Bifidobacterium, Fae- calibacterium prausnitzii, and Akkermansia muciniphila). Improvements in insulin sensitivity, lipid profiles, inflammatory biomarkers, and hepatic fat content are often accompanied by such microbial alterations. Fifteen studies provided direct evidence that dietary modulation of the microbiota leads to quantifiable metabolic effects. Current RCT evidence supports the potential of dietary interventions to modulate the gut microbiota and promote metabolic health. Findings highlight the potential of microbiome-targeted nutritional interventions within precision medicine and public health policy, as well as the need for longer-term, mechanistically detailed, and geographically diverse trials.

Keywords

Introduction

Background
The gut microbiota, a complex community of microorganisms residing within the human gastrointestinal system, is crucial for overall health and homeostasis. The gut microbiota plays a crucial role in multiple physiological functions, including digestion, the immune system, and neurological signaling. It has been emphatically established that gut microbiota plays a crucial role in controlling host metabolism, protecting against pathogens, and regulating the immune system [1, 2].
Diet is one of the predominant factors that influence the composition of gut microbiota. Nutrient intake is a source of nutrients upon which the microbiota are sustained, and it is well known that brief alterations in diet can cause demonstrable changes in microbiota composition. Indeed, dietary interventions have demonstrated that changes in macronutrient content lead to substantial modifications in the gut ecosystem within a short period, with dramatic changes in bacterial populations occurring within 24 hours [3].
These alterations entail not only shifts in microbial composition but also in function, including the production of metabolites such as short-chain fatty acids (SCFAs), which are reported to be critical modulators of inflammation, lipid metabolism, and insulin sensitivity.
Recent evidence also emphasizes a strong association between host gut microbiota and metabolic disorders such as obesity, type 2 diabetes (T2D), and metabolic syndrome (MetS). The microbial balance, known as dysbiosis, is often disrupted in patients with metabolic diseases. These changes are characterized by derangement of intestinal barrier function, low-grade systemic inflammation, and disturbed energy metabolism [4]. Furthermore, microbial metabolites, such as imidazole propionate, have been linked to the development of insulin resistance, suggesting a direct mechanistic relationship between microbial activity and the host’s metabolic health.
Existing Research Gaps
Although there is an increasing body of literature on gut microbiota, dietary factors, and metabolic diseases, little attention has been paid to the interaction between these factors; most studies have considered them as independent or univariate parameters in the long term. For example, microbiota is described as being shaped by diet and as contributing to metabolic diseases through dysbiosis, but is rarely discussed as one vertex of an entangled and dynamic triangle with nutrition and host metabolism. This fragmented strategy has so far hindered knowledge about the role of dietary components in shaping microbial communities and how this contributes to the development or aggravation of metabolic diseases. Accordingly, a comprehensive overview of the relationship between diet, gut microbiota, and metabolic health is warranted.
Rationale for Scoping Review
The complexity of interactions among gut microbiota, diet, and metabolic diseases demands a comprehensive and integrated view of the current literature. A weakness of conventional systematic reviews is the limitation to specific interventions or outcomes, which may miss overarching trends and contextual considerations. A scoping review is well-suited to explore new, complex, or diverse bodies of evidence in which the evidence is heterogeneous concerning study design, population, and/or conceptual focus [5].
As the gut microbiota literature is also growing rapidly, a growing body of evidence is pointing to a unique yet interrelated role of diet within microbial ecosystems and vice versa, with microbial ecosystems affecting metabolic health-related conditions (i.e., obesity, diabetes, and cardiovascular disease) [1]. Yet, the three dimensions are rarely assessed simultaneously in an integrated fashion. Thus, in a scoping review employing the enhanced methodology proposed by Peters et al, there is a critical need to systematically catalog triangular interactions, compare key findings, and identify gaps for cross-disciplinary integration [6].
Objectives and Research Questions
1. To survey the current literature on the triangular connection of gut microbiota-diet-metabolic diseases.
2. To investigate how diet influences the gut microbiota.
3. To determine the mechanisms by which alterations in gut microbiota composition and function promote the development and progression of metabolic diseases.
4. To identify evidence gaps and recommend avenues for research.
5. To evaluate whether integrated approaches involving diet and microbiota can be effectively leveraged for metabolic disease prevention and management.

Materials and Methods

Protocol and Registration
This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. No formal protocol was registered for this review. However, the methodology was developed in accordance with the frameworks established by Arksey and O’Malley [5] and further refined by Peters et al [6].
Eligibility Criteria
The inclusion criteria were:
• Peer-reviewed journal articles published up to and including May 2025.
• Studies written in English.
• Research involving only adult human subjects.
• Randomized controlled trials (RCTs) examining all three di- mensions: diet, gut microbiota, and metabolic disease. Excluded were:
• Non-English publications, pediatric-related studies, commen- taries, editorials, and abstracts without a full text.
• Animal studies, in vitro studies.
The rationale was to include the most relevant, up-to-date, and scientifically rigorous evidence to comprehensively map the tri- angular relationship between diet, gut microbiota, and meta- bolic disease.
Information Sources
Databases searched included:
• PubMed
• Web of Science
• Cochrane
The most recent search was conducted on May 3, 2025.
Search
The search strategy involved keyword combinations such as (“gut microbiota” OR “microbiome”) AND (“diet” OR “nutrition”) AND (“metabolic syndrome” OR “obesity” OR “diabetes”). Boolean operators (AND/OR) and truncation (e.g., microb*) were used to optimize sensitivity and specificity. Search filters lim- ited results to English-language articles published up to and including May 3, 2025.
Selection of Sources of Evidence
The search yielded 2,615 articles from PubMed, Scopus, and the Cochrane Library. Rayyan Duplicate Detection identified 1065 duplicate records. Following manual screening, 541 duplicate articles were removed, 503 were resolved, and 21 were identified as non-duplicates, resulting in 1,550 records for screening.
Two reviewers independently conducted title and abstract screening using the Rayyan software. Conflicts were flagged by the system and resolved through discussion. Following the inclusion and exclusion criteria, 671 full-text articles were reviewed. Finally, 49 RCTs were identified that met the inclusion criteria and were included in the review.
Data Charting Process
Information was graphed using a pre-created extraction form, which was piloted and used by the review team to modify the list. Data were extracted independently by two reviewers in duplicate. Differing opinions were resolved by consensus.
Data Items
The following variables were extracted from each included study: author(s), year, country, study design and population characteristics, type of dietary exposure (e.g., fiber, fat, specific diets), microbiota-related outcomes (e.g., diversity, SCFA production), metabolic health outcomes (e.g., BMI, insulin resistance, lipid profiles), and key findings along with reported study limitations. A summary of the 49 RCTs incorporated into this scoping review is presented in Table 1. These findings elucidate the complex relationship among diet, gut microbiota, and metabolic health. Studies were described according to their design, population, and dietary intervention, or relationship with the gut microbiota and metabolic parameters, and included key findings and limitations, with a synthesis of evidence across different dietary exposures and health outcomes.
Critical Appraisal of Individual Sources of Evidence
Only RCTs were included in the scoping review, as stipulated at the outset through the inclusion criteria, to ensure methodological quality and uniformity of evidence sources. A formal critical appraisal or risk of bias assessment was not performed a priori, as per the adopted scoping review methodology. However, the RCT-only paradigm generates a basic level of trust in the review of evidence about diet and gut microbiota interactions and metabolic health.

Results

Selection of Sources of Evidence
A total of 2,615 records were identified through a comprehensive database search on the relationship between diet, gut microbiota, and metabolic health. After duplicate removal using Rayyan, 2,074 unique records remained for screening. Titles and abstracts were independently screened by two reviewers, resulting in 671 studies for full-text review based on the inclusion criteria of human RCTs reporting both microbiota and metabolic outcomes. Of these, 49 RCTs met all criteria and were included in the final synthesis. Exclusions were primarily due to study design (non-RCT), population (non- human or pediatric), lack of relevant outcomes, or absence of a defined dietary intervention. The full selection process is summarized in Figure 1 (PRISMA-ScR flow diagram).
Characteristics of Sources of Evidence
This review includes 49 randomized controlled trials (RCTs) conducted across 26 countries, reflecting the global scope of research on the diet–microbiota–metabolism axis. Study durations ranged from 4 to 24 weeks, though precise averages were inconsistently reported. Most trials followed rigorous methodological designs, particularly double-blind, placebo- controlled protocols, enhancing internal validity.
The dietary interventions were diverse, spanning isolated compounds (e.g., inulin, Camu-camu polyphenols), whole-food approaches (e.g., high-fiber rye or legume-based diets), and synbiotic formulations. The most frequent strategies involved:
(1) polyphenol-rich supplements compared to placebo, (2) high-fiber cereal interventions (e.g., 30 g/day of rye), and (3) combinations of fiber and fat (e.g., Camelina oil with resistant dextrin).
Outcomes assessed included gut microbial diversity and abundance, particularly taxa like Bifidobacterium and Faecalibacterium, alongside key metabolic indicators such as glycemic control, lipid profiles, inflammation, and anthropometrics. While the overall evidence supports diet- induced microbial modulation with metabolic benefits, considerable variability in intervention types, endpoints, and study populations limits direct comparability.
A detailed summary of each included study, including design, population, dietary exposure, microbiota effects, metabolic outcomes, and limitations, is presented in Table 1.
To highlight geographic trends in the evidence base, Table 2 summarizes all included RCTs conducted in Asia, detailing their unique interventions and outcomes. The table presents the study designs, interventions, microbiota, and metabolic outcomes, as well as key findings and reported limitations.
Table 2 details the subset of RCTs conducted in European countries, demonstrating the diversity of interventions tested and the microbiota-metabolic patterns observed within Western dietary contexts. Provides a summary of RCTs from North, Central, and South America, highlighting region-specific dietary exposures and their microbiome-mediated effects on metabolic health. Table 2 summarizes studies conducted in cross-continental (e.g., Europe/Asia) and less-represented regions such as Australia, offering complementary perspectives to the regional analyses.
Critical Appraisal within Sources of Evidence
Consistent with the established scoping review methodology, a formal critical appraisal of the sources of evidence was not conducted [5]. The procedure aligns with the purpose of a scoping review, which is to identify the extent and nature of the research rather than to assess the risk of bias or methodological quality.
However, all studies in this review were RCTs, which were defined a priori at the most stringent level of acceptable evidence in the inclusion criteria. By limiting inclusion to RCTs only, the review maintains a consistent threshold for methodological quality across sources.
This criterion enhances the internal validity and robustness of conclusions drawn from the pooled estimates while also allowing for the breadth of study populations, intervention types, and outcomes measured, which is characteristic of the diet-microbiota-metabolism field.
Diet and Gut Microbiota
A variety of dietary interventions demonstrated clear effects on gut microbial profiles. For instance, Rustanti et al. [11] documented a remarkably higher abundance of Lactobacillus plantarum after probiotic administration in women with T2D and downstream effects on the relative abundance of other taxa, such as Faecalibacterium. Salazar et al. [12] reported that inulin-type fructans promoted the growth of particular Bifidobacterium spp. and inversely correlated with the concentration of SCFAs in feces. Iversen et al. [13] found that a rye diet resulted in an increased abundance of butyrate- producing taxa, such as Agathobacter. On the other hand, a polyphenol- and fiber-fortified functional beverage has been shown to increase microbial diversity, although no modification in alpha diversity indexes was observed [14]. These examples illustrate that a myriad of dietary inputs can differentially impact the microbial ecology, frequently favoring the growth of SCFA producers or barrier-supporting bacteria. Figure 3 is a graphical overview of the systemic effects of obese-type gut microbiota and microbial interactions with host physiology. The illustration is provided to visually integrate how obese-type gut microbiota efforts impact various metabolic organs and pathways together (e.g., host appetite, inflammation, and lipid and glucose metabolism).
Microbiota and Metabolic Diseases
Microbial changes that correlated with beneficial changes in host metabolic markers were also observed in multiple studies. Kanazawa et al. [15] recently reported that the use of a synbiotic was associated with increased levels of Bifidobacterium adolescentis and short-chain fatty acids (SCFAs), with a concurrent decrease in insulin resistance in obese adults with T2D. Medina-Vera et al. [16] found that endotoxemia and inflammation were reduced after a functional food intervention in T2D patients , and this reduction correlated with higher levels of Akkermansia muciniphila. Horvath et al. [17] also associated higher levels of Faecalibacterium prausnitzii with lower IL-6 and better lipid profiles, thereby strengthening the relationship between gut microbiota and systemic metabolic regulation.
Triangular Studies: Diet Microbiota Metabolic Improvement
Several studies presented evidence along the complete diet--microbiota--metabolism axis. Gao et al. [9] reported that a polyphenol-enriched Mediterranean diet modulates bile acid signaling and enhances Roseburia and lipid metabolism. Gómez- Pérez et al. [7] reported that fiber-induced microbial richness was associated with lower hepatic fat and C-reactive protein (CRP) among patients with non-alcoholic fatty liver disease (NAFLD). In a cross-over trial, Capurso et al. [18] reported that sourdough bread intake increased gastrointestinal symptoms, as well as an abundance of Bifidobacterium, but failed to affect systemic biomarkers. Together, these trials suggest that specific dietary alterations can reprogram the microbiota, resulting in corresponding improvements in clinical symptoms.
Synthesis of Results
The 49 RCTs reviewed highlight three interconnected themes linking diet, gut microbiota, and metabolic health. First, diets rich in fermentable fibers, polyphenols, and unsaturated fats modulated microbial communities, especially favoring SCFA- producing taxa, with whole-food approaches yielding stronger effects than isolated nutrients. Second, changes in gut microbiota often correlated with improved metabolic markers such as insulin sensitivity and reduced inflammation mediated by microbial metabolites like SCFAs and bile acids, though effects varied by individual baseline profiles. Lastly, studies addressing the full diet–microbiota–metabolism pathway provided the strongest evidence for causality, though metabolic benefits were sometimes modest despite significant microbiota shifts.
Figure 3 provides a summary of the triangular correlation, where various dietary types, including high-fiber, Mediterranean, and Western diets, affect gut microbiota ecology and metabolism, which subsequently impact key metabolic and glycemic outcome measures, such as insulin sensitivity, BMI, and hepatic fat levels.
Trends and Limitations
Heterogeneity in response, however, also illustrates the complexity of analyzing host-microbiome interactions within humans. Across the body of evidence, it is apparent that diversity consistently stands out as a marker of health and resilience. Primary limitations included the short duration of interventions, restricted geographical sampling, and the lack of mechanistic data to connect certain microbes with specific outcomes. However, these shortcomings do not detract from the consistent conclusion that the microbiome is a critical determinant that mediates dietary effects on chronic metabolic diseases.

Discussion

This scoping review sought to systematically map and synthesize RCT evidence investigating the impact of dietary interventions on gut microbiota composition and its impact on metabolic health outcomes. By limiting inclusion to RCTs in human adults, the review is biased toward a high level of internal validity and methodological quality, thereby enabling stronger inferences about potential causal relationships. This finding was consistent with the primary purpose of elucidating how individual dietary components affect the microbiome and, in turn, influence host metabolism [5].
The RCTs included provide consistent support for three fundamental conceptual themes that frame our synthesis. Diet as a driver of gut microbiota modulation was found in almost all included studies. Nutritional interventions with fermentable fibers, resistant starches, polyphenol-rich plant foods, and fermented dairy products have been demonstrated to modulate the microbial community structure, thereby increasing the diversity and abundance of health-associated taxa. Notably, taxa such as Bifidobacterium, Faecalibacterium prausnitzii, and Akkermansia muciniphila were commonly enriched after these interventions, echoing previous observations on the association of this microbiota with a favorable metabolic profile [2, 3].
Moreover, the role of the gut microbiota as a mediator of metabolic end-points was robustly supported by trials that correlated changes in the microbiota with changes in insulin sensitivity, blood lipids, circulating levels of inflammatory markers (e.g., C-reactive protein [CRP]), and hepatic fat content. Most of these effects were attributed to microbial metabolites, including short-chain fatty acids (SCFAs) and secondary bile acids, which act on host receptors to regulate glucose and lipid homeostasis [4].
Although the studies were part of a global collaborative research project, low-income and middle-income countries were still underrepresented, contributing to cultural and dietary homogeneity in the evidence. The underrepresentation limits inferences to other dietary customs and microbiomes adapted to different ecological pressures.
In sum, the implications of the results are general. It can be suggested that targeted dietary recommendations modulating the microbiota can be considered an adjuvant for metabolic disease prevention and treatment. Future studies will need to prioritize specific microbial players and bioactive metabolites, particularly SCFAs, as therapeutic targets. Lastly, public health advocates can utilize this burgeoning evidence to lobby for microbiome-informed dietary guidelines aimed at enhancing both gut and metabolic health at a population level [2, 4].

Limitations

This review followed Arksey and O’Malley’s framework [5], which emphasizes mapping evidence rather than evaluating study quality, limiting conclusions about trial rigor or bias. Many included RCTs were short-term and involved diverse populations with varying metabolic conditions, complicating comparisons and generalizability. Mechanistic data (e.g., metagenomics, metabolomics) were often lacking, making it difficult to interpret causal pathways linking microbiota shifts to metabolic changes. These limitations highlight the need for future trials that are longer, mechanistically rich, and methodologically standardized to more precisely uncover how dietary interventions impact gut microbiota and metabolic health.

Conclusion

This scoping review confirms that dietary interventions can significantly modulate the gut microbiota, with downstream effects on metabolic health. The strongest evidence comes from studies examining the full diet–microbiota–metabolism axis, particularly those showing increased SCFA production and reduced inflammatory markers like CRP. These findings highlight the potential for crop-specific and microbiome- targeted nutrition to improve metabolic outcomes such as insulin sensitivity, lipid profiles, and inflammation. Moreover, the review underscores the promise of personalized nutrition strategies integrating gut microbial profiling for preventing and managing conditions like obesity, type 2 diabetes, and NAFLD. To move the field forward, future research should focus on longer-term, geographically diverse RCTs with standardized multi-omics and microbiota methodologies to better capture host–microbe metabolic interactions.

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