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Diet provides a safe and attractive alternative to available treatment options in a variety of diseases; however, research has only just begun to elucidate the role of diet in chronic diseases, such as the inflammatory bowel diseases (IBD). The chronic and highly debilitating IBDs, Crohn disease and ulcerative colitis, are hallmarked by intestinal inflammation, immune dysregulation, and dysbiosis; and evidence supports a role for genetics, microbiota, and the environment, including diet, in disease pathogenesis. This is true especially in children with IBD, where diet-based treatments have shown excellent results. One interesting group of dietary factors that readily links microbiota to gut health is dietary fibers. Fibers are not digested by human cells, but rather fermented by the gut microbes within the bowel. Evidence has been mounting over the last decade in support of the importance of dietary fibers in the maintenance of gut health and in IBD; however, more recent studies highlight the complexity of this interaction and importance of understanding the role of each individual dietary fiber subtype, especially during disease. There are roughly ten subtypes of dietary fibers described to date, categorized as soluble or insoluble, with varying chemical structures, and large differences in their fermentation profiles. Many studies to date have described the benefits of the byproducts of fermentation in healthy individuals and the potential health benefits in select disease models. However, there remains a void in our understanding of how each of these individual fibers affect human health in dysbiotic settings where appropriate fermentation may not be achieved. This review highlights the possibilities for better defining the role of individual dietary fibers for use in regulating inflammation in IBD.

Background: The fermentation of dietary fibers (DF) leads to the production of bioactive metabolites, the most volatile ones being excreted in the breath. The aim of this study was to analyze the profile of exhaled breath volatile metabolites (BVM) and gastro-intestinal symptoms in healthy volunteers after a single ingestion of maltodextrin (placebo) versus chitin-glucan (CG), an insoluble DF previously shown to be fermented into short-chain fatty acids (SCFA) by the human microbiota in vitro.Methods: 4.5 g maltodextrin (day 0) or 4.5 g CG (day 2) were added to a standardized breakfast in fasting healthy volunteers (n=15). BVM were measured using selected ion flow tube mass spectrometry (SIFT-MS) throughout the day, as well as gastrointestinal tolerance by using validated visual analogue scale. Faecal gut microbiota (Illumina 16S rRNA sequencing) and SCFA (gas chromatography with flame-ionization detection) were analyzed prior to intervention. Results: A single ingestion of 4.5 g CG did not induce significant gastrointestinal discomfort. Untargeted metabolomics analysis of breath highlighted that 13 MS-fragments (among 408 obtained from ionizations of breath) discriminate CG versus maltodextrin acute intake in the postprandial state. Targeted analysis revealed that CG increased exhaled butyrate, but also 5 other BVM – including the microbial metabolites 2,3-butanedione and 3-hydroxybutanone – with a peak observed 6h after CG intake. Correlation analyses spotlighted Mitsuokella as a potential genus responsible for the presence of butyric acid, triethylamine and 3-hydroxybutanone in the breath.Conclusion: Measuring BMV in the breath reveals the microbial signature of the fermentation of DF after a single ingestion. This standardized protocol allows to analyze the time-course of released bioactive metabolites that could be proposed as new biomarkers of DF fermentation, potentially linked to their biological properties.

Additional file 1: Figure S1. Flow chart summarizing subject flow through the study.

Background Variability in the health effects of dietary fiber might arise from inter-individual differences in the gut microbiota’s ability to ferment these substrates into beneficial metabolites. Our understanding of what drives this individuality is vastly incomplete and will require an ecological perspective as microbiomes function as complex inter-connected communities. Here, we performed a parallel two-arm, exploratory randomized controlled trial in 31 adults with overweight and class-I obesity to characterize the effects of long-chain, complex arabinoxylan (n = 15) at high supplementation doses (female: 25 g/day; male: 35 g/day) on gut microbiota composition and short-chain fatty acid production as compared to microcrystalline cellulose (n = 16, non-fermentable control), and integrated the findings using an ecological framework. Results Arabinoxylan resulted in a global shift in fecal bacterial community composition, reduced α-diversity, and the promotion of specific taxa, including operational taxonomic units related to Bifidobacterium longum, Blautia obeum, and Prevotella copri. Arabinoxylan further increased fecal propionate concentrations (p = 0.012, Friedman’s test), an effect that showed two distinct groupings of temporal responses in participants. The two groups showed differences in compositional shifts of the microbiota (p ≤ 0.025, PERMANOVA), and multiple linear regression (MLR) analyses revealed that the propionate response was predictable through shifts and, to a lesser degree, baseline composition of the microbiota. Principal components (PCs) derived from community data were better predictors in MLR models as compared to single taxa, indicating that arabinoxylan fermentation is the result of multi-species interactions within microbiomes. Conclusion This study showed that long-chain arabinoxylan modulates both microbiota composition and the output of health-relevant SCFAs, providing information for a more targeted application of this fiber. Variation in propionate production was linked to both compositional shifts and baseline composition, with PCs derived from shifts of the global microbial community showing the strongest associations. These findings constitute a proof-of-concept for the merit of an ecological framework that considers features of the wider gut microbial community for the prediction of metabolic outcomes of dietary fiber fermentation. This provides a basis to personalize the use of dietary fiber in nutritional application and to stratify human populations by relevant gut microbiota features to account for the inconsistent health effects in human intervention studies. Trial registration Clinicaltrials.gov, NCT02322112, registered on July 3, 2015.

Additional file 5: Table S3. Fecal pH, moisture content, and concentrations and percentages of fecal short-chain fatty acids. Table provides the actual values, relative changes, and q values of fecal pH, fecal moisture content, and fecal concentration and relative percentage of short-chain fatty acids measured as a response to 6-week arabinoxylan or microcrystalline cellulose supplementation (related to Fig. 5a)

Additional file 9: Figure S6. Individualized SCFA response to arabinoxylan could not be explained by baseline diet, stool consistency, or bowel movement (BM) frequency during treatment. Heatmap shows the associations between the individualized SCFA response (acetate, propionate, butyrate; dependent variable; columns) and either (A) baseline diet or (B) stool consistency and BM frequency (predictors; rows). For A and B, cells represent individual multiple linear regression models (with FDR correction) that assess whether the predictors explain the individualized SCFA responses. Multivariate diet data were simplified into principal component (PC) variables PC1, PC2, and PC3 prior to analysis. Each model contained either the calorie-adjusted intakes of total grains, whole grains, total fiber, or total supplemental fiber; stool consistency or BM frequency; or the best one or two diet PCs as the predictors (PCs selected by stepwise regression). All models were adjusted by fiber dose/sex. Colors from white to red indicate relative AICc (corrected Akaike information criterion) values calculated by (AICc value / Highest AICc value) x 100. Lower AICc values (red) indicate higher quality models. AX, arabinoxylan; BL, baseline; MCC, microcrystalline cellulose; SCFA, short-chain fatty acid; W6, week 6

Additional file 8: Figure S5. Individualized acetate and butyrate response to arabinoxylan could be explained by baseline and shifts of the gut microbiota. Heatmap shows the associations between the individualized response of (A) acetate and (B) butyrate (ΔW6–BL; dependent variable; columns) and microbiota profiles (BL, ΔW1–BL, ΔW6–BL; predictors; rows). Cells represent individual multiple linear regression models (with FDR correction) that assess whether the predictors explain the individualized SCFA responses. Multivariate microbiota data were simplified into principal component (PC) variables PC1, PC2, and PC3 prior to analysis. Each model contained the best one or two predictors of PCs, individual CARGs, or significant OTUs selected by stepwise regression. All models were adjusted by fiber dose/sex. Colors from white to red indicate relative AICc (corrected Akaike information criterion) values calculated by (AICc value / Highest AICc value) x 100. Lower AICc values (red) indicate higher quality models. AX, arabinoxylan; BL, baseline; CARG, co-abundance response group; MCC, microcrystalline cellulose; OTU, operational taxonomic unit; W1, week 1; W6, week 6

IntroductionDietary fibers (DF) are considered as beneficial nutrients for health. Current data suggest that their interaction with the gut microbiota largely contributes to their physiological effects. The FiberTAG project(1) innovates in searching for new biomarkers reflecting the health effect of dietary fibers, including chitin-glucan (CG, extracted from the fungal exoskeleton Aspergillus niger). CG improves metabolic disorders associated with obesity in mice, but its effect on gut microbiota composition and function has never been evaluated in vivo in humans.Materials and MethodsCG (KitoZyme, Belgium) was given to healthy volunteers (n = 15), during three weeks (4.5g/day). Volatile Organic Compound (VOC) metabolites released in breath were analyzed using SYFT methodology. Fatty acid (FA) profiling was assessed in stool samples, by gas-liquid chromatography(2). The gut microbiome was analyzed by Illumina sequencing (V5-V6 region of 16S rRNA).ResultsThree weeks of CG supplementation was well tolerated and lead to changes in the kinetics of breath VOC, especially the short-chain fatty acid, alcohols and alkanes. Fecal vaccenic acid, produced upon the bacterial metabolism of fatty acids, was significantly increased by CG. Several bacterial genera were correlated with breath VOC (i.e. 2 methylbutyric acid and RuminococcaceaeUCG005). Moreover, Roseburia, often presented as a butyrate producer, was positively correlated with the production of a rumenic acid isomer “cis-9,cis-11-18:2”.DiscussionWe show that breath VOC analysis, a non-invasive methodology, reveals characteristics of microbiota-CG interactions. We also show that CG selectively changes the profile of FA metabolites, in favor of vaccenic acid, another bioactive metabolite produced by Roseburia, prone to act on host physiology. This study will help to establish a set of new biomarkers linking insoluble DF and gut microbiota, with focus on their interest in human health.

Additional file 3: Table S2. The relative abundance of bacterial taxa and co-abundance response groups (CARGs) affected by the dietary interventions as assessed by 16S rRNA gene amplicons sequencing. Table provides the relative abundances, relative changes, and q values of dominant bacterial taxa and CARGs affected by 6-week consumption of either arabinoxylan or microcrystalline cellulose (related to Fig. 2e). Data provided as mean ± SD

Additional file 4: Figure S2. Baseline fecal microbiota composition and diet showed no association with the individualized microbiota response to arabinoxylan. (A) Heatmap shows the associations between microbiota compositional shifts (ΔW6–BL; dependent variables; columns) and baseline microbiota profiles (predictors; rows). (B) Heatmap shows the association between microbiota compositional shifts (ΔW6–BL; dependent variables; columns) and the baseline diet variables (predictors; rows). For both A and B, cells represent individual multiple linear regression models (with FDR correction) that assess whether the predictors explain the individualized compositional shifts. Multivariate microbiota and diet data were simplified into principal component (PC) variables PC1, PC2, and PC3 prior to analysis. Each model contained the best one or two predictors of PCs (microbiota and diet), individual CARGs, or significant OTUs (predictors selected by stepwise regression), or either total grains, whole grains, or total fiber alone. All models were adjusted by fiber dose/sex. Colors from white to red indicate relative AICc (corrected Akaike information criterion) values calculated by (AICc value / Highest AICc value) x 100. Lower AICc values (red) indicate higher quality models. AX; arabinoxylan; BL, baseline; CARG, co-abundance response group; MCC, microcrystalline cellulose; OTU, operational taxonomic unit; W1, week 1; W6, week 6

Additional file 7: Figure S4. Temporal propionate response to arabinoxylan supplementation showed no association with baseline diet. (A) Principal component analysis plot based on Euclidean distance comparing the baseline, calorie-adjusted intake of Canada’s 2007 Food Guide food group and macronutrient variables between W6-responders (red) and W6-nonresponders (black). Data were analyzed using PERMANOVA. (B) Comparison between W6-responders (red) and W6-nonresponders (black) in the calorie-adjusted intakes of single dietary factors (total grains, whole grains, total fiber, and arabinoxylan [AX] supplement) performed using Mann-Whitney tests. W1, week 1; W6, week 6

Additional file 2: Table S1. Subject characteristics at baseline. Table provides a list of the subject characteristics assessed at baseline, with subjects grouped based on their randomization to either the arabinoxylan or microcrystalline cellulose treatment arm. Data provided as mean ± SD or as a percentage

Dietary fibers (DFs) impact the gut microbiome in ways often considered beneficial. However, it is unknown if precise and predictable manipulations of the gut microbiota, and especially its metabolic activity, can be achieved through DFs with discrete chemical structures. Using a dose-response trial with three type-IV resistant starches (RS4s) in healthy humans, we found that crystalline and phosphate cross-linked starch structures induce divergent and highly specific effects on microbiome composition that are linked to directed shifts in the output of either propionate or butyrate. The dominant RS4-induced effects were remarkably consistent within treatment groups, dose-dependent plateauing at 35 g/day, and can be explained by substrate-specific binding and utilization of the RS4s by bacterial taxa with different pathways for starch metabolism. Overall, these findings support the potential of using discrete DF structures to achieve targeted manipulations of the gut microbiome and its metabolic functions relevant to health.

Fecal microbiota transplantation (FMT) is a gut microbial-modulation strategy that has been investigated for the treatment of a variety of human diseases, including obesity-associated metabolic disorders. This study appraises current literature and provides an overview of the effectiveness and limitations of FMT as a potential therapeutic strategy for obesity and metabolic syndrome (MS). Five electronic databases and two gray literature sources were searched up to 10 December 2018. All interventional and observational studies that contained information on the relevant population (adult patients with obesity and MS), intervention (receiving allogeneic FMT) and outcomes (metabolic parameters) were eligible. From 1096 unique citations, three randomized placebo-controlled studies (76 patients with obesity and MS, body mass index = 34.8 ± 4.1 kg/m2, fasting plasma glucose = 5.8 ± 0.7 mmol/L) were included for review. Studies reported mixed results with regards to improvement in metabolic parameters. Two studies reported improved peripheral insulin sensitivity (rate of glucose disappearance, RD) at 6 weeks in patients receiving donor FMT versus patients receiving the placebo control. In addition, one study observed lower HbA1c levels in FMT patients at 6 weeks. No differences in fasting plasma glucose, hepatic insulin sensitivity, body mass index (BMI), or cholesterol markers were observed between two groups across all included studies. While promising, the influence of FMT on long-term clinical endpoints needs to be further explored. Future studies are also required to better understand the mechanisms through which changes in gut microbial ecology and engraftment of microbiota affect metabolic outcomes for patients with obesity and MS. In addition, further research is needed to better define the optimal fecal microbial preparation, dosing, and method of delivery.

Knowledge about the development of the preterm infant gut microbiota is emerging and is critical to their health. Very-low-birth-weight (VLBW; birth weight,1500 g) infants usually have special dietary needs while showing increased oxidative stress related to intensive care. This prospective cohort study assessed the effect of feeding practice on gut microbiome development and oxidative stress in preterm infants. Fecal samples were collected from each infant in the early (1-2 weeks of enteral feeding) and late (2-4 weeks of enteral feeding) feeding stages. We performed high-throughput sequencing of V3-V4 regions of the 16S rRNA gene to analyze the fecal microbiome composition of 20 VLBW preterm infants and to determine the association of gut bacterial composition with feeding practice using an oxidative stress marker (urinary F2-isoprostane). Our results showed that feeding practices in the late stage significantly influenced the gut microbiome composition and oxidative stress in preterm infants. Preterm infants fed human milk + human milk fortifier and only formula diets showed a significant increase in F2-isoprostane levels (P 0.05) compared with those fed human milk + formula diet. The gut microbiome of the infants fed the human milk + Human milk fortifier diet showed the lower relative abundance of Veillonella (P 0.05) compared with that of the infants fed the human milk + formula diet. The gut microbiome of the infants fed the only formula diet showed the lowest microbial diversity and the highest relative abundance of Terrisporobacter (P 0.05) compared with the gut microbiome of the infants fed the other diets. Correlation network analysis showed that urinary F2-isoprostane level was positively correlated with Terrisporobacter and Enterobacteriaceae abundance (P 0.05) in the preterm infants. In conclusion, these data suggest that feeding practice affects the bacterial diversity and composition in the gut microbiome and is associated with oxidative stress in VLBW preterm infants.

A total of 83 third trimester pregnant women were recruited to examine the role of pre-pregnancy versus late-pregnancy physical activity on maternal insulin resistance. Principal component analysis plots demonstrated a distinction between the high and low Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) groups. The variation was driven primarily by exercise prior to and during pregnancy. Specifically, higher levels of physical activity prior to pregnancy was associated with a lower HOMA-IR and is not modified by other variables. Women who were active prior to pregnancy were more active during pregnancy. These results suggest that being active before pregnancy may be a good strategy for mitigating the risk of insulin resistance during late pregnancy.

Weaning of pigs can lead to low-feed intake resulting in a lag in growth performance, reduced gut health, and diarrheal diseases. Epidermal growth factor (EGF), the most abundant growth factor in milk, increased weaned pig BW gain and feed efficiency in our previous work. It is believed that intestinal microbiota plays an important role in gut health and pig growth, but limited data are available on the impact of feed additives, such as EGF, on the microbial communities of the intestines. The objective of the study was to investigate if the positive influence of EGF supplementation on weight gain and gut health was related to differences in intestinal microbiota. To examine the efficacy of EGF, a 21-d animal trial was performed using 72 pigs (two equal blocks of 36 pigs with three barrows and three gilts/pen). Pigs were assigned to one of two dietary treatments at weaning (20 ± 2 d of age; n = 6 pens/treatment) balancing across treatment for litter, gender, and initial BW. Recombinant yeast supernatant containing EGF at 120 μg/kg BW/d and without EGF (control) was added to the feed for 21 d, followed by a common diet for 7 d. Pig performance was measured weekly and ileal digesta was collected at day 21 from six pigs/treatment for microbiome analysis. Pigs fed diets containing EGF fermentation supernatant had greater (P = 0.01) daily gain in week 3 and overall resulting in heavier (P = 0.029) BW at day 28, which was consistent to our previous finding. No difference in alpha-diversity (Chao1, Shanon, and Simpson indices) and beta-diversity (weighted and unweighted UniFrac distances) of ileal digesta microbiota between EGF supplemented and control pigs were observed. The relative abundances of bacterial taxa did not differ among treatment groups at the phylum level. The relative abundances of Corynebacterium (0.0 vs. 0.9%), Blautia (0.003 vs. 0.26%), and Coprococcus (0.0 vs. 0.05%) genera, and Rumminococcaceae family (0.001 vs. 0.08%) were decreased (P < 0.05) in EGF group compared to control and were negatively correlated (P < 0.05, r > 0.60) with growth performance. Pathways related to detoxification and carbohydrate metabolism were differentially represented in the luminal bacterial populations. The improved growth of pigs supplemented with EGF supernatant produced by Pichia pastoris may be related to changes in functional capacity of the gut microbial populations. However, the impact on mucosa-associated or large intestinal communities is still unknown.

The immunomodulatory activity of the arabinoxylans (AXs) extracts from cereal sources has beenreported to impart health benefits in terms of immune enhancement. This study investigated the effect ofenzymatic extraction on extraction yield and structure of AXs from wheat flour pentosan fraction. Underthe optimised conditions, the extraction yield of AXs reached up to 81.25%. Furthermore, the studydetermined whether water-extracted AXs (WEAXs) and enzyme-extracted AXs (E-WEAXs) from wheatflour were able to differentially stimulate nitric oxide (NO) secretion through increased levels of induciblenitric oxide synthase (iNOS) in human U937 monocytes. The results indicated that AXs concomitantlyinduced (P < 0.05) both NO and iNOS productions in U937 monocytes compared to untreated cells.Compared with WEAXs, E-WEAXs resulted in a higher proportion of low Mw (1– 10 KDa) AXs(49.51% vs. 19.11% in WEAXs), a higher A/X ratio (0.83 vs. 0.48 in WEAXs) and a higher yield(12.83  0.35% vs. 7.54  0.47% in WEAXs). Moreover, E-WEAXs induced significantly (P < 0.05)greater NO and iNOS production per million viable cells (61.8  2.7 lM and 42.41  3.83 ng respec-tively) than WEAXs (51.6  2.6 lM and 33.46  1.48 ng, respectively). The findings suggest AXs mayheighten innate immune activity in the absence of infection or disease through an iNOS-mediated stimula-tion of NO production. The immunomodulatory activity of the wheat-derived AXs was enhanced byenzyme treatment, with low Mw and high A/X ratio associated with elevated NO/iNOS levels in humanmonocytes compared to water extraction.

Arabinoxylans (AXs) are one of the most important groups of hemicelluloses in the endosperm and outer layers of cereal grains. However, the macromolecular characteristics of extracted AXs and the extraction yields achieved exhibit huge differences. These differences are apparently dependent on the different extraction and modification methods used. This paper aims to review the extraction and modification methods used in the separation of AXs from cereal by-products as reported in previous studies. The effects of different extraction and modification methods on AX extraction yields, molecular characteristics and properties were evaluated. The influence of various extraction methods including chemical solvent extraction, enzymatic extraction and modification, and mechanically-assisted extraction on molecular structure (the ratio of arabinose to xylose and molecular weight distribution) of AXs are compared and discussed in this paper.

The limitation of 16S rRNA gene sequencing (DNA-based) for microbial community analyses in water is the inability to differentiate live (dormant cells as well as growing or non-growing metabolically active cells) and dead cells, which can lead to false positive results in the absence of live microbes. Propidium-monoazide (PMA) has been used to selectively remove DNA from dead cells during downstream sequencing process. In comparison, 16S rRNA sequencing (RNA-based) can target live microbial cells in water as both dormant and metabolically active cells produce rRNA. The objective of this study was to compare the efficiency and sensitivity of DNA-based, PMA-based and RNA-based 16S rRNA Illumina sequencing methodologies for live bacteria detection in water samples experimentally spiked with different combination of bacteria (2 gram-negative and 2 gram-positive/acid fast species either all live, all dead, or combinations of live and dead species) or obtained from different sources (First Nation community drinking water; city of Winnipeg tap water; water from Red River, Manitoba, Canada). The RNA-based method, while was superior for detection of live bacterial cells still identified a number of 16S rRNA targets in samples spiked with dead cells. In environmental water samples, the DNA- and PMA-based approaches perhaps overestimated the richness of microbial community compared to RNA-based method. Our results suggest that the RNA-based sequencing was superior to DNA- and PMA-based methods in detecting live bacterial cells in water.

© 2016 American Chemical Society. The ingestion of foods and food-derived substances that may mediate the immune system is widely studied. Evidence suggests cereal arabinoxylans (AXs) have immunomodulatory activities that may impart health benefits in terms of immune enhancement. This study extracted AXs from corn bran using alkali and developed a modification process using three endoxylanases to obtain fractions of lower molecular weight ranges. In vitro studies showed extracted and modified AXs significantly (P < 0.05) elevated nitric oxide (NO) synthesis by the human U937 monocytic cell line (ranging from 53.7 ± 1.1 to 62.9 ± 1.2 μM per million viable cells) at all concentrations tested (5-1000 μg/mL), indicative of immune enhancement compared to an untreated control (43.7 ± 1.9 μM per million viable cells). The study suggested the dose range and Mw distribution of AXs are key determinants of immune-modulatory activity. AXs in the low Mw range (0.1-10 KDa) were the most effective at inducing NO secretion by U937 macrophages at low AX concentration ranges (5-50 μg/mL), with NO production peaking at 62.9 ± 1.2 μM per million viable cells with 5 μg/mL of AX (P = 0.0009). In contrast, AXs in the high Mw range (100-794 kDa) were most effective at inducing NO at high AX concentration ranges (500-1000 μg/mL) with NO production reaching a maximum of 62.7 ± 1.3 μM per million viable cells at 1000 μg/mL of AX (P = 0.0011). The findings suggest that dietary AXs from corn bran may heighten innate immune responses in the absence of infection or disease.

OBJECTIVES: The gut microbiota is linked to a wide range of pathologies, making it a promising target for improving health. Modulation of the gut microbiota can be achieved by dietary fibers, such as resistant starches, which have demonstrated a role in the prevention of these diseases. However, it is unknown if targeted manipulation of gut microbiota composition, and especially function can be achieved by specific doses of structurally similar yet district fibers. The objective of this study was to compare the effect and dose-response of three different type-4 resistant starches (RS4s) on microbiome composition and function. METHODS: Using a randomized, double blind, placebo controlled, four arm design, 40 subjects were assigned to consume either one of three RS4s (derived from hi-maize, potato, or tapioca) or a digestible starch for 4 weeks. The fiber dose was raised each week from 0 to 50 g/d, and fecal samples were collected at the end of each week. Microbiota composition and SCFA were assessed by 16S RNA gene sequencing and gas chromatography, respectively. RESULTS: Maize and tapioca RS4s, at doses ≥35 g/d, significantly affected the global composition of the microbiota, decreasing α-diversity and increasing β-diversity compared to baseline. Interestingly, effects of RS4s on microbiota composition and fecal SCFA were distinct and reflected differences in RS4 structure. Maize RS4 enriched Operational Taxonomic Units related to Eubacterium rectale [100% ID], Ruminococcus spp [97.9% ID], and Bifidobacterium adolescentis [100% ID], and increased butyrate. Although there was overlap in the enrichment of B. adolescentis, tapioca RS4 enriched Parabacteroides distasonis [100% ID] and Eisenbergiella spp [94% ID] (but not E. rectale or Ruminococcus spp), and increased propionate. These affects were dose-dependent with a plateau at the 35 g/d dose. In contrast, potato RS4 and digestible starch did not significantly modulate the microbiome. CONCLUSIONS: These findings provide essential information on how chemical differences in starch structure can result in specific and dose-dependent alterations of the gut microbiome, providing a basis for precision microbiome modulation through nutritional strategies. FUNDING SOURCES: This work was supported by Ingredion Incorporated, and by the Campus Alberta Innovation Program, CIHR, and the Canada Foundation for Innovation.