Search Results (20)

Irritable bowel syndrome (IBS) is a prevalent yet poorly understood functional gut disorder frequently associated with microbial dysbiosis, making microbiome-targeting interventions a promising management strategy. In this study, we evaluated the microbiome-modulating potential of three doses of triacetin (TA; ReBiome™; 100, 200 and 300 mg/day) and two finished formulations containing TA and/or tributyrin (TB): Active Biome™ (AB) and Bio Complete 3™ (BC3). Inulin served as a benchmark prebiotic. The validated ex vivo Systemic Intestinal Fermentation Research (SIFR^®) technology pipeline was applied using fecal microbiota from eight adults with IBS. TA dose-dependently increased short-chain fatty acid (SCFA) levels from 100 mg/day, significantly increasing acetate and butyrate while maintaining low gas formation. In addition to acetate and butyrate, AB and BC3 also promoted propionate while BC3 induced a particularly pronounced butyrate increase. Overall, both formulations induced stronger SCFA but milder gas increases than inulin. TA, AB and BC3 enriched IBS-depleted, butyrate-associated OTUs related to Faecalibacterium and Anaerobutyricum species. AB and BC3 increased microbial diversity (community modulation score (CMS)) by promoting Bifidobacteriaceae, Lachnospiraceae and Bacteroidaceae. Overall, TA and TA/TB-containing formulations promoted butyrate production, potentially helping mitigate IBS symptom severity by inducing a favorable fermentation profile with limited gas formation. Full article

Perfluorooctanoic acid (PFOA) is an environmentally persistent chemical that enters the gastrointestinal tract (GIT) via the food chain, posing a harmful, long-term threat to human health. In response to this challenge, research on the PFOA-GIT interaction is thriving. Currently, studies on the effect of PFOA on the epithelial cells of the GIT and those on its influence on the microbial community are often implemented separately, and less attention has been paid to the combinational effects of the chemical, the gut microbiome and metabolome. In the present study, we co-cultured fecal samples from healthy adults aged 25–70 in the ex vivo SIFR^® simulator, adding PFOA at 10 mg/L to represent the accumulated effects of long-term exposure. The results obtained from bacterial cell counting by flow cytometry and shotgun metagenomic sequencing revealed that PFOA was broadly disruptive to the microbiome and that Pseudomonadota emerged as the dominant phylum by replacing Bacteriodota and Bacillota, including key members of short-chain fatty acid-producing groups. Bacterial culture media with and without PFOA were collected and used in human colonoid cell culture for TEER and transcription measurement. It was shown that the PFOA-impacted microbial culture had stronger effects on the cell’s protective functions, in terms of tissue junction tightening, mucin biosynthesis, and immune response, than either untreated bacterial culture or PFOA alone. The results point out the possibility that the combination of PFOA and PFOA-impacted bacterial metabolites more strongly induces a change in epithelial cells’ protective function than either one alone. Full article

Background: Gut microbiome-derived metabolites, particularly short-chain fatty acids (SCFA) and tryptophan derivatives, are central mediators of the gut–brain axis. This ex vivo study assessed how nutritional interventions impact such metabolites during early life, a critical period for neurodevelopment. Methods: The effects of galacto-oligosaccharides (GOS), nutrient blends (vitamins, minerals and amino acids) and their combinations were evaluated in the gut microbiomes of infants (2–4 months, n = 6) and young children (2–3 years old, n = 6) using the ex vivo SIFR^® technology. Results: Baseline microbiome composition was age-dependent, with infants displaying lower α-diversity and greater interpersonal variability. After ex vivo incubation, nutrient blends increased the propionate/butyrate ratio and branched-chain fatty acids in young children and elevated several B-vitamins and amino acid-derived metabolites, including indole-3-carboxaldehyde, imidazoleacetic acid and pipecolinic acid. Combining nutrient blends with GOS exhibited potential synergistic effects on propionate (infants) and 2-hydroxyisocaproic acid (HICA, both age groups). GOS strongly stimulated Bifidobacteriaceae and increased metabolites linked to bifidobacterial metabolism like acetate, HICA, N-acetylated amino acids, aromatic lactic acids and acetylagmatine; in young children, butyrate and γ-aminobutyric acid (GABA) also increased. Conclusions: Combinations of GOS with nutrient blends impacted microbiome-derived metabolites associated with the gut–brain axis, with potential synergistic increases of metabolites with emerging roles in neurodevelopment, including GABA, acetylagmatine and HICA. Despite shared bifidogenic effects, differences between age groups indicate that microbiome maturity may influence responses to nutritional intervention. Future clinical studies are needed to determine whether these metabolite changes translate into neurodevelopmental benefits in vivo. Full article

In this study, we developed an eco-friendly intumescent flame-retardant coating for polyester (PET) fabrics. The coating was formulated with aluminum diethylphosphinate-based flame retardant (P-FR), trisilanol isobutyl-POSS (Si-FR), sericin (SC), and poly(vinyl alcohol) (PVA), using citric acid (CA) as a chemical crosslinker. The coatings were applied to alkaline-treated PET fabrics via the knife-coating technique, followed by drying and curing. P-FR acted as the primary flame-retardant component, while SC and Si-FR served as N/Si synergistic agents that enhanced the performance of P-FR, as demonstrated by an improvement in the UL 94 rating from V-1 to V-0. Thermogravimetric analysis indicated that SC and Si-FR improved the oxidative stability of the char. Flame-retardant finishing increased the limiting oxygen index (LOI) from 21.1% for untreated fabric to 31.7% for treated fabric, while tensile strength increased and elongation at break decreased. Notably, after 50 washing cycles, the treated fabrics retained self-extinguishing behavior, although the UL 94 classification decreased to V-2. Overall, this halogen-free coating system effectively enhanced the flame retardancy of PET fabrics while using environmentally friendly components, indicating its potential for sustainable flame-retardant textile applications. Full article

Background: Gut barrier dysfunction and altered gut microbial metabolism are emerging signatures of chronic gut disorders. Considering growing interest in combining structurally and mechanistically distinct bioactives, we investigated the individual and combined effects of serum-derived bovine immunoglobulin (SBI) and N-acetylglucosamine (NAG) on the gut microbiome and barrier integrity. Methods: The validated ex vivo SIFR^® (Systemic Intestinal Fermentation Research) technology, using microbiota from healthy adults (n = 6), was combined with a co-culture of epithelial/immune (Caco-2/THP-1) cells. Results: While SBI and NAG already significantly improved gut barrier integrity (TEER, transepithelial electrical resistance, +21% and +29%, respectively), the strongest effect was observed for SBI_NAG (+36%). This potent combined effect related to the observation that SBI and NAG each induced distinct, complementary shifts in microbial composition and metabolite output. SBI most selectively increased propionate (~Bacteroidota families) and health-associated indole derivatives (e.g., indole-3-propionic acid), while NAG most specifically boosted acetate and butyrate (~Bifidobacteriaceae, Ruminococcaceae, and Lachnospiraceae). The combination of SBI_NAG displayed effects of the individual ingredients, thus, for instance, enhancing all three short-chain fatty acids (SCFA) and elevating microbial diversity (CMS, community modulation score). Conclusions: Overall, SBI and NAG exert complementary, metabolically balanced effects on the gut microbiota, supporting combined use, particularly in individuals with gut barrier impairment or dysbiosis linked to lifestyle or early-stage gastrointestinal disorders. Full article

Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder, characterized by abdominal pain, altered bowel habits (diarrhea and/or constipation) and a dysbiosis of the gut microbiome. This dysbiosis is difficult to restore via fiber supplementation, which typically promotes gas production, potentially worsening IBS symptoms. We therefore studied how two novel products, triacetin (TA; REBiome™) and a mushroom blend (MB; Hōlistiq™), modulate the microbiome of IBS subjects (n = 8) using the ex vivo SIFR^® (Systemic Intestinal Fermentation Research) technology combined with a co-culture of epithelial/immune (Caco-2/THP-1) cells. First, the IBS microbiomes revealed large interpersonal variability and an IBS-associated dysbiosis. TA increased the beneficial metabolites acetate and butyrate (~Anaerobutyricum soehngenii, Mediterraneibacter_A butyricigenes, Faecalibacterium prausnitzii). Moreover, MB stimulated a wide range of gut microbes and additionally promoted propionate. Despite more strongly increasing total short-chain fatty acid (SCFA) levels, TA induced significantly less gas production than MB. Mechanistically, acetate with TA was derived from hydrolysis, a process that indeed does not induce gas production. Notably, both TA and MB enhanced gut barrier integrity (transepithelial electrical TEER), which is related to lower symptom severity in IBS patients. Overall, our findings highlight the product-specific microbiome modulation and potential of MB, TA or combinations thereof as dietary interventions for managing IBS symptom severity. Full article

The food additive sodium benzoate (SB) has been used for decades as an antimicrobial to prevent food spoilage. SB has been deemed to pose no risk to human health when consumed at levels under 5 mg/kg body weight per day; however, when many of the supporting studies were conducted, the importance of the gut microbiome to human health was not yet appreciated. Given SB’s known antimicrobial qualities, it is important to assess the effect of this food additive on the human gut microbiome. The ex vivo SIFR^® (Systemic Intestinal Fermentation Research) technology was used to test the effect of SB on microbial communities from 24 donors, aged infants to older adults. A dose of 3.5 g/L SB elicited a drop in the Pseudomonadota phylum for multiple age groups but did not alter the alpha or beta diversity within any of these groups. This was accompanied by changes in the functional outputs that included an overall rise in butyrate and a drop in propionate production. This higher butyrate correlates with an increase in the abundance of several known butyrate producers in the presence of SB, although the genetic potential for its production in the community did not change. Overall, despite using a dose ten times higher than the accepted daily intake limit, the effect on the gut microbiome was minimal. Full article

Background: Prebiotics are selectively used by host microorganisms to promote health. Because effective prebiotic doses (1.5–30 g/day) often require inconvenient delivery formats, this study aims to explore whether capsule-compatible doses of galacto-oligosaccharides (GOS) can effectively modulate the gut microbiome. Methods: The impact of Bimuno^® GOS (Reading, UK) at 0.5, 0.75, 1.83, and 3.65 g on the adult gut microbiome was assessed using the ex vivo SIFR^® technology (n = 8), a clinically validated, bioreactor-based technology. Results: The GOS were rapidly fermented and significantly increased beneficial Bifidobacterium species (B. adolescentis, B. bifidum, and B. longum), even at the lowest tested dose. In doing so, GOS strongly promoted SCFA production, particularly acetate (significant from 0.5 g) and butyrate (significant from 0.75 g). Gas production only mildly increased, likely as Bifidobacterium species do not produce gases. Based on the ability of the SIFR^® technology to cultivate strictly anaerobic, hard-to-culture gut microbes, unlike in past in vitro studies, we elucidated that GOS also enriched specific Lachnospiraceae species. Besides Anaerobutyricum hallii, this included Bariatricus comes, Blautia species (B. massiliensis, Blautia_A, B. faecis), Oliverpabstia intestinalis, Mediterraneibacter faecis, and Fusicatenibacter species. Finally, GOS also promoted propionate (significant from 0.75 g), linked to increases in Phocaeicola vulgatus. Conclusions: GOS displayed prebiotic potential at capsule-compatible doses, offering greater flexibility in nutritional product formulation and consumer convenience. Notably, the strong response at the lowest dose suggests effective microbiome modulation at lower levels than previously expected. Full article

Background: The human gut microbiota develops in concordance with its host over a lifetime, resulting in age-related shifts in community structure and metabolic function. Little is known about whether these changes impact the community’s response to microbiome-targeted therapeutics. Providing critical information on this subject, faecal microbiomes of subjects from six age groups, spanning from infancy to 70-year-old adults (n = six per age group) were harvested. The responses of these divergent communities to treatment with the human milk oligosaccharide 2’-fucosyllactose (2’FL), fructo-oligosaccharides (FOS), and lactose was investigated using the Ex vivo SIFR^® technology that employs bioreactor fermentation and is validated to be predictive of clinical findings. Additionally, it was evaluated whether combining faecal microbiomes of a given age group into a single pooled microbiome produced similar results as the individual microbiomes. Results: First, marked age-dependent changes in community structure were identified. Bifidobacterium levels strongly declined as age increased, and Bifidobacterium species composition was age-dependent: B. longum, B. catenulatum/pseudocatenulatum, and B. adolescentis were most prevalent for breastfed infants, toddlers/children, and adults, respectively. Metabolomic analyses (LA-REIMS) demonstrated that these age-dependent differences particularly impacted treatment effects of 2’FL (more than FOS/lactose). Further analysis revealed that while 2’FL enhanced production of short-chain fatty acids (SCFAs) and exerted potent bifidogenic effects, regardless of age, the specific Bifidobacterium species enhanced by 2’FL, as well as subsequent cross-feeding interactions, were highly age-dependent. Furthermore, single-pooled microbiomes produced results that were indicative of the average treatment response for each age group. Nevertheless, pooled microbiomes had an artificially high diversity, thus overestimating treatment responses (especially for infants), did not recapitulate interindividual variation, and disallowed for the correlative analysis required to unravel mechanistic actions. Conclusions: Age is an important factor in shaping the gut microbiome, with the dominant taxa and their metabolites changing over a lifetime. This divergence affects the response of the microbiota to therapeutics, demonstrated in this study using 2’FL. These results evidence the importance of screening across multiple age groups separately to provide granularity of how therapeutics impact the microbiome and, consequently, human health. Full article

Background: Using dietary interventions to steer the metabolic output of the gut microbiota towards specific health-promoting metabolites is often challenging due to interpersonal variation in treatment responses. Methods: In this study, we combined the ex vivo SIFR^® (Systemic Intestinal Fermentation Research) technology with untargeted metabolite profiling to investigate the impact of carrot-derived rhamnogalacturonan-I (cRG-I) on ex vivo metabolite production by the gut microbiota of 24 human adults. Results: The findings reveal that at a dose equivalent to 1.5 g/d, cRG-I consistently promoted indole-3-propionic acid (IPA) production (+45.8% increase) across all subjects. At a dose equivalent to 0.3 g/d, increased IPA production was also observed (+14.6%), which was comparable to the effect seen for 1.5 g/d inulin (10.6%). IPA has been shown to provide protection against diseases affecting the gut and multiple organs. The Pearson correlation analysis revealed a strong correlation (R = 0.65, p_adjusted = 6.1 × 10⁻¹⁶) between the increases in IPA levels and the absolute levels of Bifidobacterium longum, a producer of indole-3-lactic acid (ILA), an intermediate in IPA production. Finally, the community modulation score, a novel diversity index, demonstrated that cRG-I maintained a high α-diversity which has previously been linked to elevated IPA production. Conclusions: The results from the ex vivo SIFR^® experiment mirrored clinical outcomes and provided novel insights into the impact of cRG-I on the gut microbiome function. Importantly, we demonstrated that cRG-I promotes tryptophan conversion into IPA via gut microbiome modulation, thus conferring benefits via amino acid derived metabolites extending beyond those previously reported for short chain fatty acids (SCFA) resulting from carbohydrate fermentation. Full article

The prevalence of pediatric inflammatory bowel disease (pIBD) has been increasing over the last two decades. Yet, treatment strategies are still limited, in part due to the multifactorial nature of the disease and the complex interplay between genetic, environmental, dietary, immune, and gut microbial factors in its etiology. With their direct and indirect anti-inflammatory properties, human milk oligosaccharides (HMOs) are a promising treatment and management strategy for IBD. However, to date there are no insights into how HMOs may affect pIBD microbiota. Here, we compared the effects of 2′fucosyllactose (2′FL), difucosyllactose (DFL), 3′sialyllactose (3′SL), and blends thereof with fructooligosaccharide (FOS) on microbiota functionality (short- and branched-chain fatty acids, pH, and gas production) and composition (quantitative shallow shotgun sequencing) using fecal material from eight different pediatric Crohn’s disease patients inoculated in the SIFR^® technology. In general, all HMO treatments significantly increased total short-chain fatty acid production when compared with FOS, despite equal gas production. We found that 2′FL, either alone or in combination with DFL and 3′SL, exhibited a strong acetogenic and propiogenic effect, and 3′SL an acetogenic effect that surpassed the effects observed with FOS. No differences in overall community diversity between HMO- and FOS-treated pIBD microbiota were observed. There was, however, a stronger bifidogenic effect of 2′FL, 3′SL, 2′FL/DFL, and 2′FL/DFL + 3′SL when compared with FOS. In general, 3′SL and HMO blends enriched a broader species profile, including taxa with potentially anti-inflammatory properties, such as Faecalibacterium prausnitzii and Blautia species. This study suggests HMOs as a promising strategy to beneficially alter the gut microbial profile in pIBD. Full article

GoodBiome™ Foods are functional foods containing a probiotic (Bacillus subtilis HU58™) and prebiotics (mainly inulin). Their effects on the human gut microbiota were assessed using ex vivo SIFR^® technology, which has been validated to provide clinically predictive insights. GoodBiome™ Foods (BBM/LCM/OSM) were subjected to oral, gastric, and small intestinal digestion/absorption, after which their impact on the gut microbiome of four adults was assessed (n = 3). All GoodBiome™ Foods boosted health-related SCFA acetate (+13.1/14.1/13.8 mM for BBM/LCM/OSM), propionate (particularly OSM; +7.4/7.5/8.9 mM for BBM/LCM/OSM) and butyrate (particularly BBM; +2.6/2.1/1.4 mM for BBM/LCM/OSM). This is related to the increase in Bifidobacterium species (B. catenulatum, B. adolescentis, B. pseudocatenulatum), Coprococcus catus and Bacteroidetes members (Bacteroides caccae, Phocaeicola dorei, P. massiliensis), likely mediated via inulin. Further, the potent propionogenic potential of OSM related to increased Bacteroidetes members known to ferment oats (s key ingredient of OSM), while the butyrogenic potential of BBM related to a specific increase in Anaerobutyricum hallii, a butyrate producer specialized in the fermentation of erythritol (key ingredient of BBM). In addition, OSM/BBM suppressed the pathogen Clostridioides difficile, potentially due to inclusion of HU58™ in GoodBiome™ Foods. Finally, all products enhanced a spectrum of metabolites well beyond SCFA, including vitamins (B3/B6), essential amino acids, and health-related metabolites such as indole-3-propionic acid. Overall, the addition of specific ingredients to complex foods was shown to specifically modulate the gut microbiome, potentially contributing to health benefits. Noticeably, our findings contradict a recent in vitro study, underscoring the critical role of employing a physiologically relevant digestion/absorption procedure for a more accurate evaluation of the microbiome-modulating potential of complex foods. Full article

Background. Despite technical advancements, patients with sequential or diffuse coronary lesions undergoing percutaneous coronary intervention (PCI) have an increased risk of cardiovascular events at follow-up. We aimed to analyze the utility of a SyncVision/iFR (S-iFR)-guided PCI strategy versus an angiography-guided strategy in patients with this type of lesions. Methods. Randomized, multicenter, controlled, and open-label trial to compare S-iFR versus angiography-guided PCI in patients with sequential or diffuse angiographic coronary stenosis (ClinicalTrials.gov identifier: NCT04283734). The primary endpoint was the implanted stent length. The main secondary endpoint was targeting vessel failure (TVF) at one year. Results. A total of 100 patients underwent randomization, with 49 patients assigned to the S-iFR group and 51 to the angiography-guided PCI group. There were no differences between groups regarding clinical and anatomical characteristics. The baseline iFR was 0.71 ± 0.16 vs. 0.67 ± 0.19 (p = 0.279) in the S-iFR and angiography group, respectively. The mean lesion length was 42.3 ± 12 mm and 39.8 ± 12 (p = 0.297). The implanted stent length was 32.7 ± 17.2 mm in the S-iFR group and 43.1 ± 14.9 mm in the angiography group (mean difference, −10.4 mm; 95% confidence interval [CI], −16.9 to −4.0; p = 0.002). At one year, target vessel failure (TVF) occurred in four patients: three (6.1%) in the S-iFR group vs. one (1.9%) in the angiography group (p = 0.319). Conclusions. Among patients with sequential or long diffuse coronary lesions, a S-iFR-guided PCI strategy resulted in a reduction of the total stent length compared to an angiography-guided PCI strategy. A nonsignificant increase in TVF was observed in the S-iFR group. Full article

Serum-derived bovine immunoglobulin (SBI) prevents translocation and inflammation via direct binding of microbial components. Recently, SBI also displayed potential benefits through gut microbiome modulation. To confirm and expand upon these preliminary findings, SBI digestion and colonic fermentation were investigated using the clinically predictive ex vivo SIFR^® technology (for 24 human adults) that was, for the first time, combined with host cells (epithelial/immune (Caco-2/THP-1) cells). SBI (human equivalent dose (HED) = 2 and 5 g/day) and the reference prebiotic inulin (IN; HED = 2 g/day) significantly promoted gut barrier integrity and did so more profoundly than a dietary protein (DP), especially upon LPS-induced inflammation. SBI also specifically lowered inflammatory markers (TNF-α and CXCL10). SBI and IN both enhanced SCFA (acetate/propionate/butyrate) via specific gut microbes, while SBI specifically stimulated valerate/bCFA and indole-3-propionic acid (health-promoting tryptophan metabolite). Finally, owing to the high-powered cohort (n = 24), treatment effects could be stratified based on initial microbiota composition: IN exclusively stimulated (acetate/non-gas producing) Bifidobacteriaceae for subjects classifying as Bacteroides/Firmicutes-enterotype donors, coinciding with high acetate/low gas production and thus likely better tolerability of IN. Altogether, this study strongly suggests gut microbiome modulation as a mechanism by which SBI promotes health. Moreover, the SIFR^® technology was shown to be a powerful tool to stratify treatment responses and support future personalized nutrition approaches. Full article

Recent studies suggest that the dietary intake of human milk oligosaccharides (HMOs) provides health benefits from infancy up to adulthood. Thus far, beneficial changes in the adult gut microbiome have been observed at oral doses of 5–20 g/day of HMOs. Efficacy of lower doses has rarely been tested. We assessed four HMO molecular species—2′Fucosyllactose (2′FL), Lacto-N-neotetraose (LNnT), 3′Sialyllactose (3′SL), and 6′Sialyllactose (6′SL)—at predicted doses from 0.3 to 5 g/day for 6-year-old children and adults (n = 6 each), using ex vivo SIFR^® technology (Cryptobiotix, Ghent, Belgium). This technology employing bioreactor fermentation on fecal samples enables us to investigate microbial fermentation products that are intractable in vivo given their rapid absorption/consumption in the human gut. We found that HMOs significantly increased short-chain fatty acids (SCFAs), acetate, propionate (in children/adults), and butyrate (in adults) from predicted doses of 0.3–0.5 g/day onwards, with stronger effects as dosing increased. The fermentation of 6′SL had the greatest effect on propionate, LNnT most strongly increased butyrate, and 2′FL and 3′SL most strongly increased acetate. An untargeted metabolomic analysis revealed that HMOs enhanced immune-related metabolites beyond SCFAs, such as aromatic lactic acids (indole-3-lactic acid/3-phenyllactic acid) and 2-hydroxyisocaproic acid, as well as gut–brain-axis-related metabolites (γ-aminobutyric acid/3-hydroxybutyric acid/acetylcholine) and vitamins. The effects of low doses of HMOs potentially originate from the highly specific stimulation of keystone species belonging to, for example, the Bifidobacteriaceae family, which had already significantly increased at doses of only 0.5 g/day LNnT (adults) and 1 g/day 2′FL (children/adults). Full article