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The genus Senna contains globally distributed plant species of which the leaves, roots, and seeds have multiple traditional medicinal and nutritional uses. Notable chemical compounds derived from Senna spp. include sennosides and emodin which have been tested for antimicrobial effects in addition to their known laxative functions. However, studies of the effects of the combined chemical components on intact human gut microbiome communities are lacking. This study evaluated the effects of Juemingzi (Senna sp.) extract on the human gut microbiome using SIFR® (Systemic Intestinal Fermentation Research) technology. After a 48-hour human fecal incubation, we measured total bacterial cell density and fermentation products including pH, gas production and concentrations of short chain fatty acids (SCFAs). The initial and postincubation microbial community structure and functional potential were characterized using shotgun metagenomic sequencing. Juemingzi (Senna seed) extracts displayed strong, taxon-specific anti-microbial effects as indicated by significant reductions in cell density (40%) and intra-sample community diversity. Members of the Bacteroidota were nearly eliminated over the 48-hour incubation. While generally part of a healthy gut microbiome, specific species of Bacteroides can be pathogenic. The active persistence of the members of the Enterobacteriaceae and selected Actinomycetota despite the reduction in overall cell numbers was demonstrated by increased fermentative outputs including high concentrations of gas and acetate with correspondingly reduced pH. These large-scale shifts in microbial community structure indicate the need for further evaluation of dosages and potential administration with prebiotic or synbiotic supplements. Overall, the very specific effects of these extracts may offer the potential for targeted antimicrobial uses or as a tool in the targeted remodeling of the gut microbiome. [ABSTRACT FROM AUTHOR]

The current effort to valorize waste byproducts to increase sustainability and reduce agricultural loss has stimulated interest in potential utilization of waste components as health-promoting supplements. Tomato seeds are often discarded in tomato pomace, a byproduct of tomato processing, yet these seeds are known to contain an array of compounds with biological activity and prebiotic potential. Here, extract from tomato seeds (TSE), acquired from pomace, was evaluated for their ability to effect changes on the gut microbiota using an ex vivo strategy. The results found that TSE significantly increased levels of the beneficial taxa Bifidobacteriaceae in a donor-independent manner, from a range of 18.6–24.0% to 27.0–51.6% relative abundance following treatment, yet the specific strain of Bifidobacteriaceae enhanced was inter-individually variable. These structural changes corresponded with a significant increase in total short-chain fatty acids, specifically acetate and propionate, from an average of 13.3 to 22.8 mmol/L and 4.6 to 7.4 mmol/L, respectively. Together, these results demonstrated that TSE has prebiotic potential by shaping the gut microbiota in a donor-independent manner that may be beneficial to human health. These findings provide a novel application for TSE harvested from tomato pomace and demonstrate the potential to further valorize tomato waste products. [ABSTRACT FROM AUTHOR]

Low-no-calorie sweeteners (LNCS) are used as sugar substitutes as part of strategies to reduce the risk of chronic diseases related to high sugar intake (e.g. type 2 diabetes (T2D)). This study investigated how a range of sweeteners [tagatose (TA)/maltitol (MA)/sorbitol (SO)/stevia (ST)/sucralose (SU)/acesulfame K (ACK)] impact the gut microbiota of T2D subjects and healthy human adults using the ex vivo SIFR® technology (n = 12). The cohort covered clinically relevant interpersonal and T2D-related differences. ACK/SU remained intact while not impacting microbial composition and metabolite production. In contrast, TA/SO and ST/MA were respectively readily and gradually fermented. ST and particularly TA/SO/MA increased bacterial density and SCFA production product-specifically: SO increased acetate (∼Bifidobacterium adolescentis), whilst MA/ST increased propionate (∼Parabacteroides distasonis). TA exerted low specificity as it increased butyrate for healthy subjects, yet propionate for T2D subjects. Overall, LNCS exerted highly compound-specific effects stressing that results obtained for one LNCS cannot be generalised to other LNCS. [ABSTRACT FROM AUTHOR]

Introduction: While modulation of the human adult gut microbiota is a trending strategy to improve health, the underlying mechanisms are poorly understood. Methods: This study aimed to assess the predictive value of the ex vivo, reactorbased, high-throughput SIFR® (Systemic Intestinal Fermentation Research) technology for clinical findings using three structurally different prebiotics [inulin (IN), resistant dextrin (RD) and 2'-fucosyllactose (2'FL)]. Results: The key finding was that data obtained within 1-2 days were predictive for clinical findings upon repeated prebiotic intake over weeks: among hundreds of microbes, IN stimulated Bifidobacteriaceae, RD boosted Parabacteroides distasonis, while 2'FL specifically increased Bifidobacterium adolescentis and Anaerobutyricum hallii. In line with metabolic capabilities of these taxa, specific SCFA (short-chain fatty acids) were produced thus providing insights that cannot be obtained in vivo where such metabolites are rapidly absorbed. Further, in contrast to using single or pooled fecal microbiota (approaches used to circumvent low throughput of conventional models), working with 6 individual fecal microbiota enabled correlations that support mechanistic insights. Moreover, quantitative sequencing removed the noise caused by markedly increased cell densities upon prebiotic treatment, thus allowing to even rectify conclusions of previous clinical trials related to the tentative selectivity by which prebiotics modulate the gut microbiota. Counterintuitively, not the high but rather the low selectivity of IN caused only a limited number of taxa to be significantly affected. Finally, while a mucosal microbiota (enriched with Lachnospiraceae) can be integrated, other technical aspects of the SIFR® technology are a high technical reproducibility, and most importantly, a sustained similarity between the ex vivo and original in vivo microbiota. Discussion: By accurately predicting in vivo results within days, the SIFR® technology can help bridge the so-called "Valley of Death" between preclinical and clinical research. Facilitating development of test products with better understanding of their mode of action could dramatically increase success rate of microbiome modulating clinical trials. [ABSTRACT FROM AUTHOR]

Prebiotics beneficially affect the gut microbiome. Bimuno®, a prebiotic supplement containing galactooligosaccharides (GOS), has multiple demonstrated prebiotic effects. Using short-term colonic incubations, the influence of GOS on the colonic microbiota of three healthy human adults was evaluated. Colonic reactors inoculated with fecal samples were untreated (blank) or supplemented with GOS. pH, gas pressure, short-chain fatty acids (SCFAs), lactic acid, branched SCFAs, ammonium, and microbial community composition were evaluated at 0 h, 6 h, 24 h, and 48 h. pH decreased and gas pressure increased (+29.01 kPa) with GOS treatment versus blank. Total SCFA (+22.4 mM), acetate (+14.1 mM), propionate (+5.5 mM), and butyrate (+5.8 mM) were higher for GOS than blank. Acetate and propionate production were highest earlier in the experiment, while butyrate production was highest between 24 h and 48 h. With GOS, lactic acid production increased between 0 h and 6 h (+14.4 mM) followed by apparent consumption. Levels of branched SCFAs and ammonium were low with GOS and reduced versus blank (respectively, −2.1 mM and −256.0 mg/L). GOS significantly increased the relative abundance of Bifidobacterium longum (LDA = 4; p = 0.006), and significantly increased the absolute abundance of Bifidobacteriaceae (p < 0.001), Lactobacillaceae (p < 0.05), Bifidobacterium adolescentis (LDA = 4.5; p < 0.001), and Bifidobacterium ruminantium (LDA= 3.2; p = 0.01). This in vitro model demonstrated the prebiotic potential of GOS as supplementation resulted in increased beneficial bacteria, SCFA, and lactic acid and decreased branched SCFA, pH, and ammonium. [ABSTRACT FROM AUTHOR]

The American cranberry, Vaccinium macrocarpon, contains fibers and (poly)phenols that could exert health-promoting effects through modulation of gut microbiota. This study aimed to investigate how a freeze-dried whole cranberry powder (FCP) modulated metabolite production and microbial composition using both a 48-h incubation strategy and a long-term human gut simulator study with the M-SHIME (Mucosal Simulator of the Human Intestinal Microbial Ecosystem). FCP was repeatedly administered over three weeks. The studies included five and three study subjects, respectively. In both models, FCP significantly increased levels of health-related short-chain fatty acids (SCFA: acetate, propionate and butyrate), while decreased levels of branched-chain fatty acids (markers of proteolytic fermentation). Interestingly, FCP consistently increased luminal Bacteroidetes abundances in the proximal colon of the M-SHIME (+17.5 ± 9.3%) at the expense of Proteobacteria (−10.2 ± 1.5%). At family level, this was due to the stimulation of Bacteroidaceae and Prevotellaceae and a decrease of Pseudomonodaceae and Enterobacteriaceae. Despite of interpersonal differences, FCP also increased the abundance of families of known butyrate producers. Overall, FCP displayed an interesting prebiotic potential in vitro given its selective utilization by host microorganisms and potential health-related effects on inhibition of pathogens and selective stimulation of beneficial metabolites. [ABSTRACT FROM AUTHOR]

Environmental pH is a critical parameter for maintenance of the gut microbiota. Here, the impact of pH on the gut microbiota luminal and mucosal community structure and short chain fatty acid (SCFA) production was evaluated i n vitro , and data compiled to reveal a donor-independent response to an increase or decrease in environmental pH. The results found that raising environmental pH significantly increased luminal community richness and decreased mucosal community evenness. This corresponded with an increased abundance of Ruminococcaceae Ruminococcus and Erysipelotrichaceae Erysipelatoclostridium , and a decreased abundance of Coriobacteriaceae Collinsella and Enterobacteriaceae Shigella for both the luminal and mucosal communities. Total SCFA levels were significantly higher, primarily due to an increase in acetic and 2-methylbutanoic acids. Lowering pH decreased luminal community evenness and decreased mucosal community evenness and richness. This corresponded with an increased abundance of Lachnospiraceae Enterocloster, Veillonellaceae Megasphaera, Veillonellaceae Sporomusa, Erysipelotrichaceae Eubacterium , and Alcaligenaceae Sutterella , and decreased abundance of Odoribacteraceae Butyricimonas, Fusobacteriaceae Fusobacterium, Veillonellaceae Phascolarctobacterium , and multiple Enterobacteriaceae species for both the luminal and mucosal communities. Total SCFA levels were significantly lower, with an observed drop in acetic and propionic acids, and increased butyric and valeric acids. Taken together, these results indicate that alterations to environmental pH can modulate the gut microbiota community structure and function, and some changes may occur in a donor-independent manner. [ABSTRACT FROM AUTHOR]

Functional amino acids supplementation to farm animals is considered to not only be beneficial by regulating intestinal barrier, oxidative stress, and immunity, but potentially also by impacting the gut microbiota. The impact of amino acids on a piglet-derived colonic microbiota was evaluated using a 48-h in vitro batch incubation strategy. The combination of 16S rRNA gene profiling with flow cytometry demonstrated that specific microbial taxa were involved in the fermentation of each of the amino acids resulting in the production of specific metabolites. Branched chain amino acids (leucine, isoleucine, valine) strongly increased branched-chain fatty acids (+23.0 mM) and valerate levels (+3.0 mM), coincided with a marked increase of Peptostreptococcaceae. Further, glutamine and glutamate specifically stimulated acetate (~20 mM) and butyrate (~10 mM) production, relating to a stimulation of a range of families containing known butyrate-producing species (Ruminococcaceae, Oscillospiraceae, and Christensenellaceae). Finally, while tryptophan was only fermented to a minor extent, arginine and lysine specifically increased propionate levels (~2 mM), likely produced by Muribaculaceae members. Overall, amino acids were thus shown to be selectively utilized by microbes originating from the porcine colonic microbiota, resulting in the production of health-related short-chain fatty acids, thus confirming the prebiotic potential of specific functional amino acids. [ABSTRACT FROM AUTHOR]

Purpose: Cereboost®, an American ginseng extract, has shown improved short-term memory and attention/alertness in healthy young and middle-aged individuals, potentially via modulation of the gut microbiome and upregulation of neurotransmitters such as acetylcholine. Here, we explored the effects of Cereboost® on cognition and mood in the first 6 h post intervention (acute), after 2 weeks daily supplementation (chronic), and whether 2 weeks daily supplementation altered the response to a single acute dose (acute-on-chronic). A concurrent in vitro study evaluated effects of repeated Cereboost® administration on human gut microbiota. Methods: Cognitive effects of Cereboost® were assessed using a double-blind, randomized, placebo-controlled clinical trial, with 61 healthy young adults. Modulation of the gut microbiome was concurrently modelled using the Simulator of the Human Microbial Ecosystem (SHIME®), using a young adult donor. Results: Consistent with previous findings, Cereboost® improved working memory and attention during the immediate postprandial period; effects that were amplified following two weeks' treatment (acute-on-chronic) compared to acute testing alone. Chronic supplementation improved cognition on an acetylcholine-sensitive attention task and improved mental fatigue and self-assurance aspects of mood. The parallel in vitro study revealed significantly increased acetate, propionate, and butyrate levels in simulated proximal and distal colon regions, linked with observed increases in Akkermansia muciniphila and Lactobacillus. Conclusion: This study confirmed the promising effects of Cereboost® on cognitive function and mood, while suggesting a possible link to alterations of the gut microbiome and modulation of acetylcholine. Further studies will be required to unravel the underlying mechanisms that are involved. Registration: The study was pre-registered at ClinicalTrials.gov on 6th July 2018 (Identifier: NCT03579095). [ABSTRACT FROM AUTHOR]

A short-chain fructo-oligosaccharide (sc-FOS) was tested in a simulator of the human gut microbial ecosystem (SHIME) in vitro model to quantify its prebiotic effects according to Prebiotic Index (PI) and Measure of prebiotic effect (MPE) equations. FossenceTM, (sc-FOS, 0.5%) was fermented in a simulated human proximal colonic condition, using a fecal inoculum from a healthy individual. We analysed the pH reduction, substrate utilization, lactate and short-chain fatty acid (SCFA) production and microbial community modulation. Microbial fermentation of sc-FOS strongly reduced the media pH indicating the production of lactate and SCFA with accumulation of lactate and enhanced levels of acetate (34.38 ± 0.38 mM), propionate (20.93 ± 0.56 mM) and butyrate (4.93 ± 0.03 mM) compared to 18.46 ± 0.20 mM, 6.24 ± 0.10 mM and 3.3 ± 0.06 mM in the blank, respectively. Total SCFA production in test media was 61.91 ± 0.87 mM compared to 33.65 ± 0.36 mM in blank and the contribution of free-sugars present in sc-FOS to SCFAs was negligible. Modulation of the microbial community was analysed through 16S rRNA sequencing and we found that sc-FOS greatly stimulated the beneficial bacteria such as Bifidobacteria and Lactobacillus. We report the PI and MPE values for FossenceTM, as 14.9 and 0.01 respectively at the end of 24 h, which is an indicator of a strong prebiotic effect. [ABSTRACT FROM AUTHOR]

The importance of the gut microbiota in human health and disease progression makes it a target for research in both the biomedical and nutritional fields. To date, a number of in vitro systems have been designed to recapitulate the gut microbiota of the colon ranging in complexity from the application of a single vessel to cultivate the community in its entirety, to multi-stage systems that mimic the distinct regional microbial communities that reside longitudinally through the colon. While these disparate types of in vitro designs have been employed previously, information regarding similarities and differences between the communities that develop within was less defined. Here, a comparative analysis of the population dynamics and functional production of short-chain fatty acids (SCFAs) was performed using the gut microbiota of the same donor cultured using a single vessel and a 3-stage colon system. The results found that the single vessel communities maintained alpha diversity at a level comparable to the distal regions of the 3-stage colon system. Yet, there was a marked difference in the type and abundance of taxa, particularly between families Enterobacteriaceae, Bacteroidaceae, Synergistaceae, and Fusobacteriaceae. Functionally, the single vessel community produced significantly less SCFAs compared to the 3-stage colon system. These results provide valuable information on how culturing technique effects gut microbial composition and function, which may impact studies relying on the application of an in vitro strategy. This data can be used to justify experimental strategy and provides insight on the application of a simplified versus complex study design. Key points: • A mature gut microbiota community can be developed in vitro using different methods. • Beta diversity metrics are affected by the in vitro culturing method applied. • The type and amount of short-chain fatty acids differed between culturing methods. [ABSTRACT FROM AUTHOR]

The Twin Simulator of the Human Intestinal Microbial Ecosystem (TWINSHIME®) was initially developed to study the luminal gut microbiota of the ascending (AC), transverse (TC), and descending (DC) colon regions. Given the unique composition and potential importance of the mucosal microbiota for human health, the TWINSHIME was recently adapted to simulate the mucosal microbiota as well as the luminal community. It has been previously demonstrated that the luminal community in the TWINSHIME reaches a steady state within two weeks post inoculation, and is able to differentiate into region specific communities. However, less is known regarding the mucosal community structure and dynamics. During the current study, the luminal and mucosal communities in each region of the TWINSHIME were evaluated over the course of six weeks. Based on 16S rRNA gene sequencing and short chain fatty acid analysis, it was determined that both the luminal and mucosal communities reached stability 10–20 days after inoculation, and remained stable until the end of the experiment. Bioinformatics analysis revealed the formation of unique community structures between the mucosal and luminal phases in all three colon regions, yet these communities were similar to the inoculum. Specific colonizers of the mucus mainly belonged to the Firmicutes phylum and included Lachnospiraceae (AC/TC/DC), Ruminococcaceae and Eubacteriaceae (AC), Lactobacillaceae (AC/TC), Clostridiaceae and Erysipelotrichaceae (TC/DC). In contrast, Bacteroidaceae were enriched in the gut lumen of all three colon regions. The unique profile of short chain fatty acid (SCFA) production further demonstrated system stability, but also proved to be an area of marked differences between the in vitro system and in vivo reports. Results of this study demonstrate that it is possible to replicate the community structure and composition of the gut microbiota in vitro. Through implementation of this system, the human gut microbiota can be studied in a dynamic and continuous fashion. [ABSTRACT FROM AUTHOR]

The human gut contains a diverse microbiota with large potential to influence health. Given the difficulty to access the main sites of the gut, in vitro models have been developed to dynamically monitor microbial processes at the site of metabolic activity. These models range from simple batch fermentations to complex multicompartmental continuous systems. The latter include different models, focussing on similar but each also on distinct digestive parameters. The most intensively used include the three-stage continuous culture system, SHIME®, EnteroMix, Lacroix model and TIM-2. Especially after inclusion of surface-attached mucosal microbes (M-SHIME), such models have been shown representative of the in vivo situation in terms of microbial composition and activity. They have even been shown to maintain the interpersonal variation among different human fecal inocula. Novel developments, such as the incorporation of host cells, will further broaden the potential of in vitro models to unravel the importance of gut microbes for human health and disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • MegaSporeBiotic™ treatment resulted in changes that could be beneficial to the gut microbiota. • Propionate levels increased, lactate and ammonium levels decreased with treatment. • Treatment increased Akkermansia muciniphila , Bifidobacteria , and Firmicutes levels. • Bacterial diversity increased with treatment. MegaSporeBiotic™ is an oral, spore-based probiotic comprised of five Bacillus spp. (Bacillus indicus HU36, Bacillus subtilis HU58, Bacillus coagulans SC208, Bacillus licheniformis SL307, and Bacillus clausii SC109). The effects of MegaSporeBiotic™ on gut microbiota activity and community composition were evaluated for the first time using an in vitro model of the human gastrointestinal tract, the simulator of the human intestinal microbial ecosystem (SHIME®), under healthy conditions. Following a stabilization period and a control period (2 weeks each), the reactor feed was supplemented with daily MegaSporeBiotic™ for 3 weeks (treatment period). Changes in microbial community activity and composition between the control and treatment periods were evaluated for each colon compartment (ascending [AC], transverse [TC], and descending colon [DC]). Propionate levels increased significantly in the TC (week 2, P = 0.02; week 3, P = 0.0019) and DC (week 2, P = 0.03) with treatment while lactate levels significantly decreased in the TC (week 3, P = 0.03). Ammonium levels were significantly decreased during the final week of treatment (TC, P = 0.02; DC, P = 0.03). Overall, Akkermansia muciniphila , Bifidobacteria spp., and Firmicutes increased with treatment while Lactobacillus spp. and Bacteroidetes decreased. The Firmicutes:Bacteroidetes ratio increased with treatment in the AC compartment. MegaSporeProbiotic™ treatment resulted in changes in metabolism and increased bacterial diversity. [ABSTRACT FROM AUTHOR]