Chronic diseases associated with high sugar intake, such as type 2 diabetes (T2D), impact the microbiome. Low/no-calorie sweeteners are frequently used as sugar substitutes by T2D individuals, and could help in this case, but their effect on the gut microbiota has not been comprehensively studied. We conducted a preclinical research project to help shed light on the matter, using the high-throughput, ex vivo SIFR® technology, which is known for its uniquely validated ability to provide predictive insights into clinical outcomes. Our study extensively compared the impact of a broad range of sweeteners (tagatose, sorbitol, maltitol, stevia, acesulfame K and sucralose), each exhibiting distinct fermentation kinetics, on the gut microbiota of 12 co-living healthy/T2D individuals. The aim of choosing those 6 dyads, was to minimise the influence of long-term diet variations. Sweeteners like sucralose and acesulfame K did not impact microbial composition and metabolite production. In contrast, the rapidly fermented tagatose elevated propionate levels in T2D subjects, while increasing butyrate levels in healthy subjects. In addition, sorbitol strongly increased acetate (associated with Bifidobacterium adolescentis) and maltitol strongly enhanced propionate production (linked to Parabacteroides distasonis) in both donor groups. These findings indicate highly product-specific effects of the investigated sweeteners on the gut microbiota.
Investigating the effect of probiotics in the small intestine is particularly complex, due to its inaccessible location in the gastrointestinal tract. To overcome this challenge, we employed the high throughput ex vivo SIFR® technology, which is validated to provide predictive insights for clinical findings. We investigated the effects of a 9-species probiotic formula (Ecologic® 825) on the ileostoma microbiota of healthy humans. To account for interpersonal variation, we included six donors in the study. Microbial composition and metabolite production were analysed at 5 different time points, which facilitated the identification of correlations between dynamic changes in the microbial composition and metabolic fingerprints of the community. Notably, supplementation with the probiotic formula led to a decrease in ethanol production, associated with a reduction of pathobionts such as Enterococcaceae and Klebsiella pneumoniae. Additionally, the abundance of beneficial species such as Lactobacillaceae, Veillonella dispar and Anaestipes caccae resulted in a sharp increase in the levels of propionate, butyrate, and other health-related metabolites. The findings of this SIFR® study can be used to develop more effective treatments for a range of small intestinal conditions.
Gut microbiome research suffers from low predictivity, which is caused by interpersonal differences in microbiota composition. The specificity of prebiotics may be used to steer the composition of the gut microbiome and consequently guide towards more predictive research outcomes. This study compared the selectivity of carrot RG-I (cRG-I) to two other substrates, inulin (IN) and xanthan (XA), and found that cRG-I supplementation led to a homogenisation of gut microbial composition and metabolite production across individuals. This contrasted with IN and XA, which increased interpersonal differences. The study involved 24 human adults and utilized the ex vivo SIFR® technology, which combines high throughput with precision and is validated to generate predictive insights for clinical findings. Key findings from the study include that cRG-I selectively stimulated taxa consistently present among human adults, including those related to keystone species and butyrate-producing taxa. Additionally, cRG-I altered fermentation activity, producing higher acetate and propionate and generating less gas than IN. The results suggest that the specificity of cRG-I could lead to more predictable outcomes compared to less specific or overly specific substrates.
The translation of preclinical findings into valid clinical outcomes remains an issue to this day. This “Valley of Death” is very present in gut microbiome research due to the intractability of gut microbiome interactions in vivo.The ex vivo SIFR® technology successfully predicted shifts in the gut microbiota composition observed in vivo across different interventions (inulin, resistant dextrin, 2’FL). This predictivity for clinical outcomes enables the quick generation of mechanistic hypotheses, while the high throughput of the technology embraces the inter-individual variation at the preclinical stage to de-risk clinical trials on the responder/non-responder question.
There is growing awareness that interpersonal and age-dependent differences in gut microbiota composition impact prebiotic effects. The present study investigated the age-dependent prebiotic effect of fructans and HMOs in children and adults. For the fructans, inulin and FOS are well-established prebiotics. Human milk oligosaccharides (HMOs), on the other hand, are a more recent class of prebiotics that consist of a broader range of monosaccharide components and glycosidic linkage types, impacting their utilisation by the microbiota. Relying on the high throughput of the ex vivo SIFR® technology, all these actives were investigated in parallel on the gut microbiota of children and adults. The resulting compositional shift can be divided into three categories: bifidogenic across ages, for children, or for adults. Furthermore, age-specific compositional shifts occurred (B. pseudocatenulatum, and various Bacteroides spp for children; B. adolescentis, and various Phocaeicola spp). Lastly, by combining targeted analysis and untargeted metabolomics, health-promoting metabolites connected to the gut-brain axis, immunity, and overall gut health were found to be associated with those compositional changes. In conclusion, HMOs are promising modulators of the adult and particularly the children’s microbiota.
After ascertaining the prebiotic potential of tributyrin in a first study, we wanted to discover synbiotic combination further stimulating butyrate production. Relying on the high throughput of the ex vivo SIFR® technology, an exhaustive investigation was set up for the prebiotic (tributyrin) and the probiotics (Lacticaseibacillus rhamnosus GG, Limosilactobacillus reuteri), alone or in combination. To account for inter-individual variations, the gut microbiota of 6 donors was tested in parallel. The experiment confirmed that, while each molecule of tributyrin is easily converted to 3 butyrate on its own, the addition of Lacticaseibacillus rhamnosus GG or Limosilactobacillus reuteri opened an additional pathway of conversion through butyrate by first converting tributyrin-derived glycerol to lactate, which could in turn could be metabolised to butyrate by the endemic microorganism Coprococcus catus.
Various bovine plasma fractions were investigated for their prebiotic potential and mechanism of action. To ensure a biorelevant research, the colonic SIFR simulation was preceded by a digestion and absorption step. The immunoglobulin fraction exhibited the most pronounced prebiotic potential. It was used specifically by Bacteroides vulgatus, Lachnoclostridium edouardi and Coprococcus comes, leading to the production of health-promoting SCFA (acetate, propionate & butyrate).