The gut microbiome plays important roles in the maintenance of host health and the pathogenesis of many diseases. Diet is a key modulator of the gut microbiome. There is increasing evidence that nutrients other than fermentable fiber affect the gut microbial composition. In this review, we discuss the effects of vitamins on the gut microbiome, and related gastrointestinal health, based on in vitro, animal and human studies. Some vitamins, when provided in large doses or when delivered to the large intestine, have been shown to beneficially modulate the gut microbiome by increasing the abundance of presumed commensals (vitamins A, B₂, D, E, and beta-carotene), increasing or maintaining microbial diversity (vitamins A, B₂, B₃, C, K) and richness (vitamin D), increasing short chain fatty acid production (vitamin C), or increasing the abundance of short chain fatty acid producers (vitamins B₂, E). Others, such as vitamins A and D, modulate the gut immune response or barrier function, thus, indirectly influencing gastrointestinal health or the microbiome. Future research is needed to explore these potential effects and to elucidate the underlying mechanisms and host health benefits.

An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.

The importance of the gut microbiota community on host’s health and disease has long been recognised and is well documented. The development of pro- and prebiotic interventions offers an opportunity for the modulation of the gut microbiota towards long lasting health. In vitro fermentation models were developed as a powerful tool to study the impact of pro- and prebiotics on the gut microbiota under tightly controlled conditions, which allow dynamic sampling over time in reactors mimicking different colon regions. These models have been further evolved to suit specific experimental purposes, e.g. including immobilised faecal microbiota, peristaltic movement, mucin microcosm and the ability to perform treatments in parallel. In this review we discuss the advantages, disadvantages and technical considerations of the most frequently used models. We further focus on recent advances in the application of these models in prebiotics and probiotics research and outline their predictability for clinical research.

Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.

The beneficial effects of prebiotic fibres on human health have been related to their capacities to alter the gut microbiota and modify the growth of beneficial microorganisms. It is long appreciated that bacterial metabolites affect the host’s physiology. The inner lining of the intestinal tract is the first level of interaction between the host and bacteria and their metabolites. Therefore, we set out to test the effects of five common dietary fibres (oat β-glucan 28%; oat β-glucan 94%; dried chicory root containing inulin 75%; xylo-oligosaccharide; inulin 90%) and maltodextrin, after fermentation by human gut microbiota in vitro, on measures of gut barrier integrity using a Caco-2/HT29-MTX co-culture as well as mucus production and immune parameters using HT29-MTX and HT29 cell models, respectively. Our data show that all fibres, fermentation products increased the tightness of the gut barrier with oat β-glucan 28% having the largest effect. Fermentation supernatants were tested also in models of the compromised gut barrier (leaky gut). After the addition of ethanol as basolateral stressor, only fermentation supernatant of oat β-glucan 28%, oat β-glucan 94% and maltodextrin improved the gut barrier integrity, while oat β-glucan 28% and dried chicory root containing inulin 75% significantly improved the gut barrier integrity after addition of rhamnolipids as apical stressor. Using the Luminex Technology, we demonstrated an important role of oat β-glucan fermentation products in modulating cytokine and chemokine productions. Furthermore, treating the goblet cells with effluent from xylo-oligosaccharide fermentation significantly increased mucus production. In summary, our data emphasize the potential positive effects of fermentation supernatant of dietary fibres on gut-related physiological outcomes and show that prebiotic fibres may have promising potential to induce specific gut health benefits.

[This corrects the article DOI: 10.7717/peerj.5288.].