Nourishing the Microbiome: Exploring the influence of Food Inflammatory Index on Gut Bacteria in Type 2 Diabetics in Saudi Arabia

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Almuhanna" }, { "@type": "Person", "name": "Rudaynah Alali" }, { "@type": "Person", "name": "Abdulmohsen H. Al Eleq" }, { "@type": "Person", "name": "Waleed I. Albaker" }, { "@type": "Person", "name": "Fatima A. Alrubaish" }, { "@type": "Person", "name": "Jana M. alsaif" }, { "@type": "Person", "name": "Chittibabu Vatte" }, { "@type": "Person", "name": "Cyril Cyrus" }, { "@type": "Person", "name": "Bao-Li Loza" }, { "@type": "Person", "name": "Raed M Alsulaiman" }, { "@type": "Person", "name": "Abdulaziz Al-Qurain" }, { "@type": "Person", "name": "Fahad A. Al-Muhanna" }, { "@type": "Person", "name": "Brendan Keating" }, { "@type": "Person", "name": "Amein Al-ali" }, { "@type": "Person", "name": "Alawi Habara" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": " Objective Diet is a key modulator of gut microbiota composition, and dietary inflammation may significantly influence metabolic disorders such as diabetes. In this study, we explored the relationship between the Food Inflammatory Index (FII) and gut microbiota composition in 234 type 2 diabetic patients from Saudi Arabia. Method A total of 234 Participants were divided into quartiles according to their FII scores, which increased progressively, effectively distinguishing varying levels of dietary inflammatory potential. Results Microbiome sequencing revealed that while overall alpha diversity remained stable, beta diversity analysis indicated subtle yet statistically significant differences in microbial community structure (PERMANOVA p = 0.001, R2 = 2.14%). At the phylum level, the dominant taxa Firmicutes and Bacteroidota, exhibited significant shifts, with a non-linear ratio of Bacteroidota to Firmicutes observed across FII quartiles. Genus-level analysis revealed significant variations in Bacteroides, Alistipes, and Prevotella_9, with pairwise comparisons highlighting marked differences between the lowest and highest FII quartiles. Conclusions These compositional changes suggest that increased dietary inflammation is linked to a shift toward a dysbiotic gut microbiota, which may exacerbate metabolic dysregulation in diabetes. These findings pave the way for future studies to investigate whether targeted, FII-guided dietary interventions can modulate gut microbial communities and enhance metabolic health in diabetic populations. 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F1000Research 2025, 14 :692 ( https://doi.org/10.12688/f1000research.165525.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Nourishing the Microbiome: Exploring the influence of Food Inflammatory Index on Gut Bacteria in Type 2 Diabetics in Saudi Arabia [version 1; peer review: 1 approved with reservations] Afnan F. Almuhanna 1 , Rudaynah Alali 2 , Abdulmohsen H. Al Eleq 2 , [...] Waleed I. Albaker 2 , Fatima A. Alrubaish 2 , Jana M. alsaif https://orcid.org/0009-0001-3381-8293 2 , Chittibabu Vatte 3 , Cyril Cyrus https://orcid.org/0000-0001-7333-6486 3 , Bao-Li Loza 4 , Raed M Alsulaiman 2 , Abdulaziz Al-Qurain 2 , Fahad A. Al-Muhanna 2 , Brendan Keating 5 , Amein Al-ali 3 , Alawi Habara https://orcid.org/0000-0002-5384-8764 3 Afnan F. Almuhanna 1 , Rudaynah Alali 2 , [...] Abdulmohsen H. Al Eleq 2 , Waleed I. Albaker 2 , Fatima A. Alrubaish 2 , Jana M. alsaif https://orcid.org/0009-0001-3381-8293 2 , Chittibabu Vatte 3 , Cyril Cyrus https://orcid.org/0000-0001-7333-6486 3 , Bao-Li Loza 4 , Raed M Alsulaiman 2 , Abdulaziz Al-Qurain 2 , Fahad A. Al-Muhanna 2 , Brendan Keating 5 , Amein Al-ali 3 , Alawi Habara https://orcid.org/0000-0002-5384-8764 3 PUBLISHED 15 Jul 2025 Author details Author details 1 Radiology, Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Eastern Province, 31441, Saudi Arabia 2 Internal Medicine, Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Eastern Province, Saudi Arabia 3 Clinical Biochemistry, Imam Abdulrahman Bin Faisal University, College of Medicine, Eastern Province, 31441, Saudi Arabia 4 Statistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA 5 Surgery, New York University Langone, New York, New York, USA Afnan F. Almuhanna Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Resources, Writing – Review & Editing Rudaynah Alali Roles: Conceptualization, Data Curation, Funding Acquisition, Investigation, Writing – Review & Editing Abdulmohsen H. Al Eleq Roles: Conceptualization, Data Curation, Funding Acquisition, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing Waleed I. Albaker Roles: Conceptualization, Data Curation, Funding Acquisition, Resources, Writing – Review & Editing Fatima A. Alrubaish Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Project Administration, Writing – Review & Editing Jana M. alsaif Roles: Data Curation, Investigation, Methodology, Resources Chittibabu Vatte Roles: Data Curation, Formal Analysis, Investigation, Methodology, Resources, Validation Cyril Cyrus Roles: Data Curation, Formal Analysis, Investigation, Methodology, Resources, Software, Writing – Original Draft Preparation Bao-Li Loza Roles: Data Curation, Formal Analysis, Methodology, Software Raed M Alsulaiman Roles: Conceptualization, Data Curation, Funding Acquisition, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Abdulaziz Al-Qurain Roles: Conceptualization, Formal Analysis, Funding Acquisition, Investigation, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Fahad A. Al-Muhanna Roles: Conceptualization, Formal Analysis, Funding Acquisition, Investigation, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Brendan Keating Roles: Conceptualization, Formal Analysis, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Amein Al-ali Roles: Conceptualization, Formal Analysis, Funding Acquisition, Investigation, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Alawi Habara Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Objective Diet is a key modulator of gut microbiota composition, and dietary inflammation may significantly influence metabolic disorders such as diabetes. In this study, we explored the relationship between the Food Inflammatory Index (FII) and gut microbiota composition in 234 type 2 diabetic patients from Saudi Arabia. Method A total of 234 Participants were divided into quartiles according to their FII scores, which increased progressively, effectively distinguishing varying levels of dietary inflammatory potential. Results Microbiome sequencing revealed that while overall alpha diversity remained stable, beta diversity analysis indicated subtle yet statistically significant differences in microbial community structure (PERMANOVA p = 0.001, R 2 = 2.14%). At the phylum level, the dominant taxa Firmicutes and Bacteroidota , exhibited significant shifts, with a non-linear ratio of Bacteroidota to Firmicutes observed across FII quartiles. Genus-level analysis revealed significant variations in Bacteroides, Alistipes, and Prevotella_9, with pairwise comparisons highlighting marked differences between the lowest and highest FII quartiles. Conclusions These compositional changes suggest that increased dietary inflammation is linked to a shift toward a dysbiotic gut microbiota, which may exacerbate metabolic dysregulation in diabetes. These findings pave the way for future studies to investigate whether targeted, FII-guided dietary interventions can modulate gut microbial communities and enhance metabolic health in diabetic populations. READ ALL READ LESS Keywords Food Inflammatory Index, Diet, Gut Microbiota, Diabetes, diet-microbiota-diabetes axis. Corresponding Author(s) Amein Al-ali ( [email protected] ) Close Corresponding author: Amein Al-ali Competing interests: No competing interests were disclosed. Grant information: This work was supported by Rawabi Scientific Chair for Regenerative & Precision Medicine, Imam Abdulrahman Bin Faisal University, Dammam and King Abdulaziz City for Science and Technology grants [# 12-MED2799-46 and13-MED1881-46]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2025 Almuhanna AF et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Almuhanna AF, Alali R, Al Eleq AH et al. Nourishing the Microbiome: Exploring the influence of Food Inflammatory Index on Gut Bacteria in Type 2 Diabetics in Saudi Arabia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :692 ( https://doi.org/10.12688/f1000research.165525.1 ) First published: 15 Jul 2025, 14 :692 ( https://doi.org/10.12688/f1000research.165525.1 ) Latest published: 15 Jul 2025, 14 :692 ( https://doi.org/10.12688/f1000research.165525.1 ) Introduction Diet plays a pivotal role in shaping gut microbiota composition, influencing metabolic pathways, immune responses, and host gene expression. As research advances, these interactions are increasingly recognized for their impact on molecular and translational medicine, bridging nutritional science, microbiome research, and clinical applications. 1 Dietary components such as fiber, polyphenols, and probiotics promote beneficial bacteria, leading to enhanced short-chain fatty acid (SCFA) production, reduced inflammation, and improved insulin sensitivity, key mechanisms in metabolic and autoimmune diseases. 1 In molecular medicine, microbiota-derived metabolites interact with host receptors, affecting pathways related to inflammation, epigenetics, and metabolic homeostasis. 2 Advances in metagenomics and metabolomics have revealed the profound role of microbiota-derived bioactive compounds in regulating host physiology and disease susceptibility. 2 By leveraging insights from microbiome research, personalized nutrition, probiotics, and fecal microbiota transplantation (FMT) have emerged as promising therapeutic strategies for managing conditions such as Type 2 Diabetes (T2D), obesity, and inflammatory diseases. Translational medicine plays a crucial role in applying these findings to develop targeted, microbiome-based interventions for improved clinical outcomes. 2 By understanding the molecular underpinnings of diet-microbiota interactions, researchers can advance precision medicine approaches to optimize disease prevention and treatment through targeted dietary interventions. 1 The FII is a tool designed to assess the inflammatory potential of foods based on their bioactive components and their effects on inflammatory biomarkers. It builds upon the Dietary Inflammatory Index (DII), which was initially developed to quantify the inflammatory potential of an individual’s diet by analyzing its relationship with inflammatory cytokines such as IL-6, CRP, and TNF-α. 3 The FII provides a more detailed evaluation by identifying the key inflammatory components within individual food items rather than broad dietary patterns. 4 Diet plays a critical role in modulating systemic inflammation, which is closely linked to metabolic disorders, including diabetes. Recent studies suggest that dietary patterns rich in anti-inflammatory foods, such as fiber-rich plant-based diets, are associated with beneficial gut microbiota composition, while pro-inflammatory diets can alter microbial diversity and promote dysbiosis. 5 Moreover, targeted dietary interventions have been shown to directly modulate gut microbiota composition, thereby influencing immune responses and inflammatory pathways. 6 Al-Muhanna et al. (2022) 7 analyzed gut microbiota in Saudi Arabian T2D patients, revealing an altered Firmicutes/Bacteroidetes ratio and enrichment of Akkermansia , Acidaminococcus , and Dialister when compared to non-T2D controls. Microbial composition correlated with glucose levels, suggesting a role in diabetes progression. Similarly, Alali et al. (2024) 8 linked plant-based diets to better glycemic control, lower triglycerides, and improved lipid profiles, while diets high in refined grains and processed foods had adverse effects. This study examines how dietary inflammatory potential, measured by the Food Inflammatory Index, affects gut microbiota at the phylum and genus levels in Saudi T2D patients, clarifying diet-microbiota interactions and metabolic health links. Given the high risk of chronic diseases like diabetes, understanding this relationship is crucial. By analyzing FII and gut microbiota composition, this study provides insights into the impact of dietary inflammation on microbial shifts in diabetic patients. Method Study population In a previous study (2015-2019) conducted on Saudi Arabian patients attending diabetic clinics at King Fahd Hospital of the University (KFHU), 16S rRNA was extracted from stool samples to analyze the microbiota communities and assess the differences based on diabetic status and glucose levels. 7 The results indicated that there were noteworthy differences on a community level between patients with T2D compared to normal in the general population, which highlighted the diversity of the Saudi Arabian population compared to Western cohorts. Consequently, it can be hypothesized that either genetic, environmental or dietary habits play a role in the formation of gut microbiota in various populations. We also subsequently conducted a dietary screening study (2017-2019) to further the research by recruiting a cohort of 577 T2D patients from the same diabetic clinics at KFHU. Nurses collected data on dietary intake using a pretested 7-day semi-quantitative food frequency questionnaire (7-d SQFFQ) designed to cover the week before the administration of the questionnaire. 8 Consequently, this validation guaranteed the accuracy and reliability of the dietary data to permit an inclusive analysis to be conducted and assess the possible impact in the management of the disease. In this study, we focused on analyzing the data of the patients who were included in both the 2015-2019 and 2017-2019 studies. As a result, a total of 234 T2D patients were included in the current analysis. We focused on this specific subcategory to discover if there were any significant associations between dietary habits and microbial communities in T2D Saudi patients to increase our knowledge of the possible connections and implications in order to manage the disease more effectively. This enabled a more detailed assessment of how dietary habits may affect gut microbiota in T2D patients. FII calculation and grouping strategy The FII was computed to assess the inflammatory potential of participants’ diets using a validated 7-d SQFFQ as previously described. 8 Reported food consumption frequencies were log-transformed to mitigate the influence of extreme consumption values and better reflect the diminishing returns in inflammatory effect observed at high intake levels. 9 , 10 Each food item was assigned an FII score (Table S1) based on established literature linking nutrients to inflammatory markers. 4 The FII score was calculated by multiplying log-transformed intake frequencies by their respective FII scores and summing across all items. Initially, participants were grouped into tertiles, but this obscured microbiota associations. Therefore, a quartile-based grouping (Q1 - Q4) was adopted which divided FII scores by percentiles (Q1 ≤ 25th, Q2: 25 th - 50th, Q3: 50 th - 75th, Q4 ≥ 75th), providing a stronger resolution of microbiota-FII relationships. Refining FII calculation and grouping improved the understanding of the impact of dietary inflammation on gut microbiota in Saudi T2D patients. Results The study included 234 patients with a mean age of 54.03 ± 9.69 years. Among them, 136 were female, and 98 were male. When categorized by FII quartiles, the mean age across quartiles showed minimal variation, ranging from 54.86 ± 10.46 years in Q1 to 53.22 ± 10.21 years in Q4. Sex distribution per quartile showed a slight variation, with females being the majority in Q2 (36 vs. 22) and Q3 (40 vs. 19), while males were slightly more prevalent in Q1 (30 vs. 29) and Q4 (27 vs. 31), Table S2. The distribution of the final FII score for the patients across the four FII quartiles is shown in Figure 1 . The FII score increased progressively and significantly (P < 0.0005) from Q1 to Q4, confirming that quartile-based grouping effectively stratified participants based on FII. Figures 2A and 2B show the histogram and Q-Q plot, respectively, and indicate that the Final FII Scores exhibit a roughly symmetrical distribution but with mild skewness and deviations at the tails. The Shapiro–Wilk test (p < 0.05) confirms that the data significantly deviates from normality, indicating a non-normal distribution. The Q-Q plot further highlights this deviation, particularly at the lower and upper extremes, where the data points diverge from the theoretical normal line. Figure 1. Final FII scores across four quartiles (Q1, Q2, Q3, Q4). Each violin depicts the spread and density of scores, with black boxplots inside indicating the median and interquartile range. Individual samples are plotted as points. Horizontal brackets with asterisks denote statistically significant pairwise comparisons; the number of asterisks corresponds to the significance level (**** p < 0.0001). Figure 2. Illustration of the distribution and normality assessment of Final FII Scores. A) Displays a histogram (blue bars) with an overlaid density curve (red line) that depicts the data distribution. B) Shows a Q–Q plot comparing the sample quantiles to the theoretical quantiles from a normal distribution. Although points near the diagonal suggest normality, systematic deviations are evident, and the Shapiro–Wilk test (p < 0.05) confirms that the data significantly deviate from a normal distribution. The Principal Coordinates Analysis (PCoA) plot visualizes the beta diversity of microbial communities across FII quartiles (Q1 - Q4), using Bray-Curtis distance ( Figure 3 ) as the dissimilarity metric. PCoA1 and PCoA2 explain 8.23% and 7.14%, respectively, of the microbial composition across the FII quartiles. The relatively low percentages suggest that microbial differences between FII quartiles are subtle but present. PERMANOVA analysis (adonis P = 0.001, R 2 = 0.0214) confirms a significant effect of FII quartiles on microbiota composition. However, the low R 2 value (2.14% variance explained) indicates that the effect size is minor, as reflected by the overlapping clusters in the PCoA plot. Figure 3. Beta diversity of microbial communities across FII quartiles. Principal Coordinates Analysis (PCoA) of microbiota composition based on Bray–Curtis distances. Each point represents an individual sample, colored by FII Quartile (Q1, Q2, Q3, Q4). The first two axes (PCoA Axis 1 and Axis 2) explain 8.23% and 7.14% of the total variation, respectively. Dashed ellipses indicate the approximate 95% confidence regions for each quartile group. Figure S1 A and B show the Shannon and Simpson alpha diversity, respectively, across FII quartiles (Q1 - Q4), with no clear trend or significant differences observed. Alpha diversity represents the richness and evenness of microbial communities within individual samples, and these results suggest that FII has a minimal impact on microbial alpha diversity in this dataset. Figure 4A shows the top 5 relative abundance of microbial taxa at the phylum level across different FII quartiles. Firmicutes and Bacteroidota dominate the distribution. Kruskal-Wallis tests revealed significant differences in the relative abundance of Firmicutes (p < 0.001) and Bacteroidota (p 0.05). The pairwise Wilcoxon test showed significant differences in Bacteroidota and Firmicutes across FII quartiles. Bacteroidota abundance differed significantly between Q1 and Q4 (p-adjusted < 0.001), Q2 and Q4 (p-adjusted = 0.032), and Q3 and Q4 (p-adjusted < 0.001). Similarly, Firmicutes showed significant differences between Q1 and Q4 (p-adjusted < 0.001), Q2 and Q4 (p-adjusted = 0.037), and Q3 and Q4 (p-adjusted < 0.001). These findings suggest that microbial composition shifts mainly occur between the extreme FII quartiles, linking dietary inflammatory potential to microbiota differences. The Bacteroidota-to-Firmicutes (B/F) ratio showed a non-linear relationship with dietary inflammation, starting high in Q1 (2.04), decreasing in Q2 (1.28), and gradually increasing in Q3 (1.55) and Q4 (1.77) as FII increased. In Q1 (lowest FII, least inflammatory diet), the high B/F ratio suggests a microbiome composition associated with a healthier metabolic state, where Bacteroidota are more abundant than Firmicutes. Table 1 summarizes the statistics for the phylum level. Figure 4. Relative abundance in percentage of the top 5 Phyla and top 10 Genera across four FII quartiles. A) A stacked bar chart shows the percentage of relative abundance for the top 5 phyla. Each bar represents the cumulative percentage of the five most prevalent phyla within that quartile, color-coded by phylum. B) A stacked bar chart illustrates the percentage of the top 10 genera in relative abundance. Each colored segment's height reflects the proportion of that genus relative to the total microbial community. Table 1. Kruskal-Wallis and Pairwise Wilcoxon Test Results for Microbial Phyla. Kruskal-Wallis tests Phylum Kruskal Statistic Degrees of Freedom P-Value Significance Firmicutes 23.60563 3 0.0000302 **** Bacteroidota 23.47334 3 0.0000322 **** Proteobacteria 4.535961 3 0.209 ns Verrucomicrobiota 2.554929 3 0.465 ns Actinobacteriota 3.331837 3 0.343 ns Bacteroidota - Pairwise Wilcoxon Group1 Group2 P-Value Adjusted P-Value Significance Q1 (Lowest) Q2 0.074 0.443 ns Q1 (Lowest) Q3 0.765 1 ns Q1 (Lowest) Q4 (Highest) 0.0000144 0.0000864 **** Q2 Q3 0.14 0.84 ns Q2 Q4 (Highest) 0.005 0.032 * Q3 Q4 (Highest) 0.0000805 0.000483 *** Firmicutes - Pairwise Wilcoxon Group1 Group2 P-Value Adjusted P-Value Significance Q1 (Lowest) Q2 0.044 0.267 ns Q1 (Lowest) Q3 0.554 1 ns Q1 (Lowest) Q4 (Highest) 0.000014 0.000084 **** Q2 Q3 0.155 0.93 ns Q2 Q4 (Highest) 0.006 0.037 * Q3 Q4 (Highest) 0.0000744 0.000446 *** Bacteroidota to Firmicutes Ratio (Relative abundance used) FII Quartile Bacteroidota Firmicutes B/F Ratio Q1 53.23 26.11 2.04 Q2 47.89 37.37 1.28 Q3 46.91 30.29 1.55 Q4 55.95 31.66 1.77 Figure 4B illustrates the top 10 relative abundance of microbiota taxa at the genus level across different FII quartiles. Bacteroides and Prevotella_9 dominated the microbial communities, constituting the majority of microbiota composition. Significant differences were observed in the abundance of Bacteroides (p < 0.001, Kruskal-Wallis), Prevotella_9 (p = 0.04), and Alistipes (p = 0.002). Figure 5 shows the log 10 relative abundance of the three significant genera across FII quartiles. Pairwise Wilcoxon tests revealed distinct patterns: Alistipes abundance notably increased from Q1 (lowest inflammation, 2.23%) to Q4 (highest inflammation, 4.03%), with significant differences specifically between Q1 and Q4 (p-adjusted = 0.002), Q2 and Q4 (p-adjusted = 0.01), and Q3 and Q4 (p-adjusted = 0.04). Bacteroides showed a nonlinear response, lowest in Q1 (37.11%) and highest in Q2 (44.22%), with significant differences observed primarily between Q1 and Q2 (p-adjusted < 0.001), Q1 and Q4 (p-adjusted = 0.001), Q2 and Q3 (p-adjusted = 0.014), and Q3 and Q4 (p-adjusted = 0.036). Prevotella_9 displayed the highest abundance in Q1 (29.71%), with a significant decrease by Q2 (18.39%, p-adjusted = 0.05). These genus-level changes highlight complex and genus-specific responses of the gut microbiota to dietary inflammatory potential (FII), underscoring notable microbial shifts associated particularly with higher dietary inflammation (Q4). Further details and complete statistics are summarized in Table 2 . Figure 5. Log 10 Relative Abundance of Alistipes, Bacteroides, and Prevotella_9 Across FII Quartiles. This figure shows boxplots overlaid with jittered data points (strip plots) for three selected genera, Alistipes, Bacteroides, and Prevotella_9, across four FII Quartiles (Q1, Q2, Q3, Q4). Each panel corresponds to one genus, and the y-axis (on a log10 scale) indicates the relative abundance of that genus in each sample. The boxplots summarize the distribution for each quartile (showing median, interquartile range, and whiskers), while the color-coded points represent individual samples. The horizontal brackets and asterisks above the boxplots denote the statistical significance of pairwise comparisons among the quartiles (*p < 0.05, **p < 0.01, ***p < 0.001). Table 2. Kruskal-Wallis and Pairwise Wilcoxon Test Results for Microbial Genera. Kruskal-Wallis tests Genus Kruskal Statistic Degrees of Freedom P-Value Significance Bacteroides 20.75 3 0.0001 *** Prevotella_9 8.29 3 0.04 * Escherichia-Shigella 2.39 3 0.5 ns Dialister 1.08 3 0.78 ns Faecalibacterium 3.45 3 0.33 ns Akkermansia 3.30 3 0.35 ns Megasphaera 2.65 3 0.45 ns UCG-002 3.17 3 0.37 ns Alistipes 14.64 3 0.002 ** Subdoligranulum 1.19 3 0.76 ns Alistipes - Pairwise Wilcoxon Group1 Group2 P-Value Adjusted P-Value Significance Q1 (Lowest) Q2 0.286 0.34 ns Q1 (Lowest) Q3 0.19 0.29 ns Q1 (Lowest) Q4 (Highest) 0.000313 0.002 ** Q2 Q3 0.762 0.76 ns Q2 Q4 (Highest) 0.003 0.01 ** Q3 Q4 (Highest) 0.02 0.04 * Bacteroides - Pairwise Wilcoxon Group1 Group2 P-Value Adjusted P-Value Significance Q1 (Lowest) Q2 0.000113 0.0007 *** Q1 (Lowest) Q3 0.262 0.31 ns Q1 (Lowest) Q4 (Highest) 0.000425 0.001 ** Q2 Q3 0.007 0.01 * Q2 Q4 (Highest) 0.694 0.69 ns Q3 Q4 (Highest) 0.024 0.04 * Prevotella_9 - Pairwise Wilcoxon Group1 Group2 P-Value Adjusted P-Value Significance Q1 (Lowest) Q2 0.008 0.05 * Q1 (Lowest) Q3 0.27 0.33 ns Q1 (Lowest) Q4 (Highest) 0.24 0.33 ns Q2 Q3 0.05 0.16 ns Q2 Q4 (Highest) 0.09 0.17 ns Q3 Q4 (Highest) 0.82 0.82 ns Discussion Intestinal microbiota plays a crucial role in metabolic inflammation, which is a key driver of T2D. This disease is often linked to gut dysbiosis characterized by a decline in beneficial, short-chain fatty acid (SCFA) producing Firmicutes and also an increased abundance of pro-inflammatory genera such as Bacteroides. 11 , 12 Diets high in fats, refined sugars, and other pro-inflammatory components, hallmarks of a Western dietary pattern, can further promote a state of chronic, low-grade inflammation. 12 This occurs, in part, via compromised gut barrier integrity, which allows lipopolysaccharides (LPS) and other microbial products to translocate into the circulation, triggering systemic inflammation that exacerbates insulin resistance, a defining feature of T2D. 11 Therefore, dietary interventions that limit pro-inflammatory components and foster the growth of SCFA-producing bacteria while enhancing gut barrier function may help reduce inflammation and improve glucose metabolism. 11 , 12 This study explored the relationship between dietary inflammatory potential, measured by the FII, and gut microbiota composition in T2D patients. Beta diversity analysis using Principal Coordinates Analysis (PCoA) revealed significant but subtle differences in microbiota composition across FII quartiles. PCoA1 and PCoA2 explained 8.23% and 7.14% of the microbial variation, respectively, while the PERMANOVA result (adonis P = 0.001, R 2 = 0.0214) indicated a statistically significant effect of dietary inflammation on gut microbiota. This suggests that while FII plays a role, other diabetes-associated factors (e.g., medication use, metabolic dysregulation, insulin resistance) likely contribute more substantially to microbiota alterations. Interestingly, alpha diversity indices (Shannon and Simpson) showed no significant differences across FII quartiles, suggesting that while microbial composition shifts occur, overall microbial richness and evenness remain stable. This finding aligns with prior research indicating that diabetes-driven microbial dysbiosis is characterized more by taxonomic composition changes rather than overall diversity loss. 13 – 15 At the phylum level, significant differences were observed in the relative abundance of Firmicutes (p = 0.00003) and Bacteroidota (p = 0.000032), with the most pronounced differences occurring between extreme quartiles (Q1 vs. Q4). The Bacteroidota-to-Firmicutes (B/F) ratio showed a non-linear relationship with dietary inflammation, starting high in Q1 (2.04), decreasing in Q2 (1.28), and gradually increasing in Q3 (1.55) and Q4 (1.77) as FII increased. In Q1 (lowest FII, least inflammatory diet), the high B/F ratio suggests a microbiome composition associated with a healthier metabolic state, where Bacteroidota are more abundant than Firmicutes. This aligns with our previous study 7 and other studies showing that diets with lower inflammatory potential are linked to an increased Bacteroidota proportion, which contributes to improved gut barrier function, enhanced fiber fermentation, and the production of anti-inflammatory metabolites. 16 – 18 The lower Firmicutes levels in Q1 could reflect a microbiome environment less influenced by inflammatory dietary components, favoring a more balanced gut microbial ecosystem that may be beneficial for metabolic health. As dietary inflammation increases (Q2 - Q4), microbiome shifts occur, with Firmicutes becoming more dominant in Q2, followed by a rebound in Bacteroidota at higher FII levels (Q3 - Q4). This pattern suggests that moderate inflammation (Q2) supports Firmicutes proliferation, potentially due to their capacity to utilize host-derived energy sources (e.g., mucin degradation) under inflammatory stress. 19 , 20 However, at higher inflammation levels (Q3 - Q4), Bacteroidota increase again, possibly due to a shift towards inflammation-associated taxa within this phylum. This non-linear microbial adaptation may reflect gut microbiota resilience or dysbiotic shifts in response to increasing inflammatory burden. Given the role of gut microbiome composition in metabolic health, these findings suggest that dietary inflammation plays a complex role in shaping gut microbial communities in diabetes. At the genus level, significant variations were identified in Bacteroides, Prevotella_9, and Alistipes, all of which belong to the phylum Bacteroidota. Specifically, Alistipes, a genus associated with anti-inflammatory properties primarily through the production of short-chain fatty acids (SCFAs), was significantly reduced in individuals consuming diets with high inflammatory potential (Q4) compared to the least inflammatory quartile (Q1). This decline in Alistipes aligns with prior studies indicating its protective role in gut barrier integrity and glucose metabolism regulation, suggesting that dietary inflammation may selectively diminish beneficial anti-inflammatory taxa. 21 – 23 Bacteroides, recognized for its metabolic flexibility and previously linked to western dietary patterns and metabolic disturbances, exhibited a nonlinear pattern across quartiles. 21 , 23 Such fluctuations may reflect adaptive microbial dynamics in response to dietary inflammatory stressors, indicating selective pressures influencing its abundance based on dietary context. Additionally, Prevotella_9, a subgroup of the Prevotella genus, is prominently involved in dietary fiber fermentation, SCFA production, and maintaining gut homeostasis, displayed significantly reduced abundance in higher dietary inflammation quartiles. The decreased abundance of Prevotella_9 suggests a disruption of anti-inflammatory microbial processes, potentially facilitating pro-inflammatory states commonly observed in metabolic disorders such as diabetes. Collectively, these genus-specific shifts, contextualized within their phylogenetic and functional backgrounds, highlight the intricate relationship between dietary inflammatory potential and microbial community structure, underscoring the potential clinical significance of microbiota-directed dietary interventions in managing inflammation and metabolic dysregulation in diabetic populations. Overall, these findings suggest that dietary inflammatory potential contributes to gut microbiota alterations in diabetes, primarily at the phylum and genus levels, rather than affecting overall diversity. However, the small effect size (R 2 = 2.14%) suggests that while the food inflammation index influences gut microbiota, other diabetes-related factors, such as hyperglycemia, insulin resistance and medication use, play a more dominant role. Chronic hyperglycemia alters microbial diversity and gut permeability, while insulin resistance and metabolic inflammation contribute to dysbiosis. Additionally, diabetic medications, such as metformin and SGLT2 inhibitors, significantly modulate the microbiome, potentially overshadowing dietary effects. Despite the valuable insights provided by this study, several limitations should be acknowledged. First, the cross-sectional design prevents establishing causal relationships between dietary inflammation, gut microbiota composition, and diabetes progression. Longitudinal studies are needed to determine the temporal effects of dietary inflammatory potential on microbiome shifts. Second, while the FII provides a useful measure of diet-induced inflammation, dietary data was self-reported, which may introduce recall bias and affect the accuracy of dietary assessments. The small R 2 may also indicate the need for a larger sample size to capture more subtle associations, highlighting the importance of further research with longitudinal data and controlled dietary interventions. Additionally, this study utilized 16S rRNA gene sequencing for microbial analysis, which, while effective for taxonomic classification at the phylum and genus levels, lacks the resolution to differentiate species and strain-level variations. Future studies should consider using shotgun metagenomic sequencing, which provides higher taxonomic resolution and functional insights into the microbial community. Incorporating metagenomics would allow a deeper understanding of how specific microbial genes and pathways interact with dietary inflammation and metabolic health. Ethical approval and consent to participate Ethical approval of the study was obtained from the Imam Abdulrahman Bin Faisal University Institutional Review Board committee, Dammam (IRB#2019-01-112), and the study was conducted according to the ethical principles of the Declaration of Helsinki and Good Clinical Practice guidelines. All patients included in the study signed a written informed consent form. Contributions AFA, RAA, AHA, WIA, FAA, JMA, CV, CC, BL, RMS, and AH were involved in the design of the work, critically revising of protocol, patient recruitment, data acquisition, interpretation of data, and drafting of the manuscript. AA, FAA, CV, BL, AKA, BK, and AH were involved in the design of the work, analysis, interpretation of data, and drafting of the manuscript. Data availability The raw 16S rRNA datasets generated during the current study are available in the European Nucleotide Archive (ENA) repository, https://www.ebi.ac.uk/ena/browser/view/PRJEB57370 , under the title “Diabetes microbiota study from a representative Saudi Population” with accession number PRJEB57370. All requests for data can be sent to the corresponding author, and verified academic investigators will be granted full access. All the values behind the means, standard deviations and other measures are reported in Supplementary tables 1, 2, 3 and 4, https://doi.org/10.5281/zenodo.15694848 . Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). 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PubMed Abstract | Publisher Full Text | Free Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 15 Jul 2025 ADD YOUR COMMENT Comment Author details Author details 1 Radiology, Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Eastern Province, 31441, Saudi Arabia 2 Internal Medicine, Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Eastern Province, Saudi Arabia 3 Clinical Biochemistry, Imam Abdulrahman Bin Faisal University, College of Medicine, Eastern Province, 31441, Saudi Arabia 4 Statistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA 5 Surgery, New York University Langone, New York, New York, USA Afnan F. Almuhanna Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Resources, Writing – Review & Editing Rudaynah Alali Roles: Conceptualization, Data Curation, Funding Acquisition, Investigation, Writing – Review & Editing Abdulmohsen H. Al Eleq Roles: Conceptualization, Data Curation, Funding Acquisition, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing Waleed I. Albaker Roles: Conceptualization, Data Curation, Funding Acquisition, Resources, Writing – Review & Editing Fatima A. Alrubaish Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Project Administration, Writing – Review & Editing Jana M. alsaif Roles: Data Curation, Investigation, Methodology, Resources Chittibabu Vatte Roles: Data Curation, Formal Analysis, Investigation, Methodology, Resources, Validation Cyril Cyrus Roles: Data Curation, Formal Analysis, Investigation, Methodology, Resources, Software, Writing – Original Draft Preparation Bao-Li Loza Roles: Data Curation, Formal Analysis, Methodology, Software Raed M Alsulaiman Roles: Conceptualization, Data Curation, Funding Acquisition, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Abdulaziz Al-Qurain Roles: Conceptualization, Formal Analysis, Funding Acquisition, Investigation, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Fahad A. Al-Muhanna Roles: Conceptualization, Formal Analysis, Funding Acquisition, Investigation, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Brendan Keating Roles: Conceptualization, Formal Analysis, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Amein Al-ali Roles: Conceptualization, Formal Analysis, Funding Acquisition, Investigation, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Alawi Habara Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information This work was supported by Rawabi Scientific Chair for Regenerative & Precision Medicine, Imam Abdulrahman Bin Faisal University, Dammam and King Abdulaziz City for Science and Technology grants [# 12-MED2799-46 and13-MED1881-46]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (1) version 1 Published: 15 Jul 2025, 14:692 https://doi.org/10.12688/f1000research.165525.1 Copyright © 2025 Almuhanna AF et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Almuhanna AF, Alali R, Al Eleq AH et al. Nourishing the Microbiome: Exploring the influence of Food Inflammatory Index on Gut Bacteria in Type 2 Diabetics in Saudi Arabia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :692 ( https://doi.org/10.12688/f1000research.165525.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 15 Jul 2025 Views 0 Cite How to cite this report: Noriega LG. Reviewer Report For: Nourishing the Microbiome: Exploring the influence of Food Inflammatory Index on Gut Bacteria in Type 2 Diabetics in Saudi Arabia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :692 ( https://doi.org/10.5256/f1000research.182167.r407156 ) The direct URL for this report is: https://f1000research.com/articles/14-692/v1#referee-response-407156 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 05 May 2026 Lilia G. Noriega , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga, Ciudad de México, Mexico Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.182167.r407156 This manuscript explores the association between the Food Inflammatory Index (FII) and gut microbiota composition in patients with type 2 diabetes. The topic is relevant, particularly given the growing interest in diet–microbiota interactions in metabolic disease. However, several aspects require ... Continue reading READ ALL This manuscript explores the association between the Food Inflammatory Index (FII) and gut microbiota composition in patients with type 2 diabetes. The topic is relevant, particularly given the growing interest in diet–microbiota interactions in metabolic disease. However, several aspects require clarification. The introduction would benefit from a clearer description of the FII, including the key dietary components that contribute to it and their known inflammatory effects. In addition, it would strengthen the rational to indicate whether the FII has previously been evaluated in relation to gut microbiota composition. Although the manuscript appears to use data derived from previous studies, essential information about the study population should be included. The authors should clarify the rationale for selecting the 234 participants included in the present analysis, and provide description of their available clinical, biochemical, and hormonal characteristics. In the introduction, the authors mention previous studies comparing individuals without type 2 diabetes and patients with type 2 diabetes. However, further justification is needed to explain why the present study evaluates only patients with type 2 diabetes and does not include a non-diabetic comparison group. The methods section requires more detail. For example, the authors should clearly describe the study type, inclusion and exclusion criteria, how microbiota composition was evaluated, and how specific measurements such as 18S rRNA were performed. Essential methodological information should not be omitted solely because the data come from previous studies. A dedicated statistical analysis section should be included in the Methods. Information about statistical tests, adjustment variables, correction for multiple comparisons, and criteria for significance should be clearly stated there rather than in the Results section. It would strengthen the manuscript to report whether clinical, biochemical, or hormonal parameters differ across FII quartiles or classifications. This would help determine whether the observed microbiota differences are associated with broader metabolic or inflammatory profiles. The authors report changes in taxa such as Bacteroides , Alistipes , and Prevotella 9 . Would it be possible to determine whether these changes are associated with specific foods or dietary components within each FII quartile? This analysis could provide more mechanistic insight into the diet–microbiota association. The Discussion should be substantially improved. The authors should avoid repeating concepts already presented in the Introduction and avoid restating the Results in excessive detail. Instead, the section should clearly summarize the main findings, explaining their biological or clinical relevance, and compare them with previous literature. In particular, with previous studies that have evaluated gut microbiota in patients with T2D or/and in relation to the FII. Although the authors acknowledge the cross-sectional or associative nature of the study as a limitation, causal language is still used throughout the manuscript. Terms implying causality should be avoided. The authors should consistently use wording such as “associated with,” “related to,” or “linked to,” rather than terms suggesting that FII causes microbiota changes. Minor Abbreviations should be defined at first mention and used consistently thereafter. Please use “patients with type 2 diabetes” instead of “diabetic patients”. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Metabolism, microbiota alterations in disease. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Noriega LG. Reviewer Report For: Nourishing the Microbiome: Exploring the influence of Food Inflammatory Index on Gut Bacteria in Type 2 Diabetics in Saudi Arabia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :692 ( https://doi.org/10.5256/f1000research.182167.r407156 ) The direct URL for this report is: https://f1000research.com/articles/14-692/v1#referee-response-407156 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 15 Jul 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 Version 1 15 Jul 25 read Lilia G. Noriega , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga, Mexico Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Noriega L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 05 May 2026 | for Version 1 Lilia G. Noriega , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga, Ciudad de México, Mexico 0 Views copyright © 2026 Noriega L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This manuscript explores the association between the Food Inflammatory Index (FII) and gut microbiota composition in patients with type 2 diabetes. The topic is relevant, particularly given the growing interest in diet–microbiota interactions in metabolic disease. However, several aspects require clarification. The introduction would benefit from a clearer description of the FII, including the key dietary components that contribute to it and their known inflammatory effects. In addition, it would strengthen the rational to indicate whether the FII has previously been evaluated in relation to gut microbiota composition. Although the manuscript appears to use data derived from previous studies, essential information about the study population should be included. The authors should clarify the rationale for selecting the 234 participants included in the present analysis, and provide description of their available clinical, biochemical, and hormonal characteristics. In the introduction, the authors mention previous studies comparing individuals without type 2 diabetes and patients with type 2 diabetes. However, further justification is needed to explain why the present study evaluates only patients with type 2 diabetes and does not include a non-diabetic comparison group. The methods section requires more detail. For example, the authors should clearly describe the study type, inclusion and exclusion criteria, how microbiota composition was evaluated, and how specific measurements such as 18S rRNA were performed. Essential methodological information should not be omitted solely because the data come from previous studies. A dedicated statistical analysis section should be included in the Methods. Information about statistical tests, adjustment variables, correction for multiple comparisons, and criteria for significance should be clearly stated there rather than in the Results section. It would strengthen the manuscript to report whether clinical, biochemical, or hormonal parameters differ across FII quartiles or classifications. This would help determine whether the observed microbiota differences are associated with broader metabolic or inflammatory profiles. The authors report changes in taxa such as Bacteroides , Alistipes , and Prevotella 9 . Would it be possible to determine whether these changes are associated with specific foods or dietary components within each FII quartile? This analysis could provide more mechanistic insight into the diet–microbiota association. The Discussion should be substantially improved. The authors should avoid repeating concepts already presented in the Introduction and avoid restating the Results in excessive detail. Instead, the section should clearly summarize the main findings, explaining their biological or clinical relevance, and compare them with previous literature. In particular, with previous studies that have evaluated gut microbiota in patients with T2D or/and in relation to the FII. Although the authors acknowledge the cross-sectional or associative nature of the study as a limitation, causal language is still used throughout the manuscript. Terms implying causality should be avoided. The authors should consistently use wording such as “associated with,” “related to,” or “linked to,” rather than terms suggesting that FII causes microbiota changes. Minor Abbreviations should be defined at first mention and used consistently thereafter. Please use “patients with type 2 diabetes” instead of “diabetic patients”. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Metabolism, microbiota alterations in disease. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Noriega LG. Peer Review Report For: Nourishing the Microbiome: Exploring the influence of Food Inflammatory Index on Gut Bacteria in Type 2 Diabetics in Saudi Arabia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :692 ( https://doi.org/10.5256/f1000research.182167.r407156) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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