Gut Function Research Articles

Impact of dietary fat types on expression levels of dopamine and serotonin transporters in the ileum of broiler chickens

Various types of dietary fats undergo distinct fermentation processes by gut microbes, potentially leading to the production of neurotransmitters that can influence the gut. Serotonin and dopamine are recognized neurotransmitters with positive effects on gut function. A broiler chicken trial was conducted to evaluate the influence of dietary fat types on protein expression of 2 neurotransmitter transporters, dopamine (DAT) and serotonin (5-HTT). A total of 560 day-old (Ross 708) male broiler chicks were randomly assigned to 7 dietary treatments. The experimental treatments included a basal diet of corn-soybean meal (SBM), supplemented with 3% of various fats: poultry fat (CON), olive oil (OLIV), fish oil (FISH), canola oil (CANO), lard (LARD), coconut oil (COCO), or flaxseed oil (FLAX). Bodyweight (BW) and feed conversion ratio (FCR) were recorded. Ileal tissues were aseptically collected to determine the expression levels of DAT and 5-HTT through western blot analysis. In addition, plasma samples were analyzed for reactive oxygen metabolites (d-ROM) tests on d 55. Results showed that dietary fat type inclusion did not have any detrimental effect on growth performance parameters. The expression levels of DAT were higher (P < 0.05) in FLAX treatments compared to CON treatments on d 20 and d 55, respectively. Similarly, with 5-HTT levels, FLAX, CANO, and LARD treatments were higher (P < 0.05) than CON treatments on d 20 and d 55. However, higher levels of oxidative stress (d-ROM values) were recorded in COCO (32.75 Carr U), CANO (29 Carr U), and CON treatments (25.5 Carr U) compared to FLAX (18.5 Carr U; P < 0.05) treatment. These findings suggest that incorporating dietary flaxseed oil at a 3% level in the diet has significant potential to elevate the expression levels of intestinal DAT and 5-HTT without inducing oxidative stress.

Low salinity stress increases the risk of Vibrio parahaemolyticus infection and gut microbiota dysbiosis in Pacific white shrimp

BackgroundExtreme precipitation events often cause sudden drops in salinity, leading to disease outbreaks in shrimp aquaculture. Evidence suggests that environmental stress increases animal host susceptibility to pathogens. However, the mechanisms of how low salinity stress induces disease susceptibility remain poorly understood.MethodsWe investigated the acute response of shrimp gut microbiota exposed to pathogens under low salinity stress. For comparison, shrimp were exposed to Vibrio infection under two salinity conditions: optimal salinity (Control group) and low salinity stress (Stress group). High throughput 16S rRNA sequencing and real-time PCR were employed to characterize the shrimp gut microbiota and quantify the severity level of Vibrio infection.ResultsThe results showed that low salinity stress increased Vibrio infection levels, reduced gut microbiota species richness, and perturbed microbial functions in the shrimp gut, leading to significant changes in lipopolysaccharide biosynthesis that promoted the growth of pathogens. Gut microbiota of the bacterial genera Candidatus Bacilliplasma, Cellvibrio, and Photobacterium were identified as biomarkers of the Stress group. The functions of the gut microbiota in the Stress group were primarily associated with cellular processes and the metabolism of lipid-related compounds.ConclusionsOur findings reveal how environmental stress, particularly low salinity, increases shrimp susceptibility to Vibrio infection by affecting the gut microbiota. This highlights the importance of avoiding low salinity stress and promoting gut microbiota resilience to maintain the health of shrimp.

Comparative impact of conventional and alternative gut health management programs on plasma and tibia attributes in broiler chickens raised in commercial and research settings

Plasma and tibia attributes were investigated in broiler chickens raised on three gut health management programs in commercial farms (study 1) and research station settings (study 2). The programs were: 1) conventional antibiotics (CON), 2) raised without medically important antimicrobials (RWMIA), and 3) raised without antibiotics (RWA). Birds had free access to feed and water from placement to harvest; samples of blood and left tibia were collected on d 28 in both studies and further samples were taken on d 41 in study 2. In both studies, there were no program differences (P &gt; 0.05) on plasma metabolites with exception of enzyme concentrations with notably higher levels of circulating plasma alkaline phosphatase (ALP) in birds reared on the RWA program (P ≤ 0.04). Differences were observed among programs for tibia length in both studies (P &lt; 0.05). Birds reared on RWMIA exhibited significantly (P = 0.016) higher tibia ash than CON on d 41. Observed differences in the plasma enzyme concentrations, tibia length, and ash concentration suggest altered metabolism which could be linked to gut health management programs and their ability to support gut integrity and function in the absence of antibiotics.

Protective role of cells and spores of Shouchella clausii SF174 against fructose-induced gut dysfunctions in small and large intestine

The oral administration of probiotics is nowadays recognized as a strategy to treat or prevent the consequences of unhealthy dietary habits. Here we analyze and compare the effects of the oral administration of vegetative cells or spores of Shouchella clausii SF174 in counteracting gut dysfunctions induced by 6 weeks of high fructose intake in a rat model. Gut microbiota composition, tight junction proteins, markers of inflammation and redox homeostasis were evaluated in ileum and colon in rats fed fructose rich diet and supplemented with cells or spores of Shouchella clausii SF174. Our results show that both spores and cells of SF174 were effective in preventing the fructose-induced metabolic damage to the gut, namely establishment of “leaky gut”, inflammation and oxidative damage, thus preserving gut function. Our results also suggest that vegetative cells and germination-derived cells metabolize part of the ingested fructose at the ileum level.

Enteral plasma feeding improves gut function and immunity in piglets after birth asphyxia.

Birth asphyxia may negatively affect gut function and immunity in newborns. Conversely, immunomodulatory milk diets may protect the gut and immune system against damage caused by asphyxia. Using caesarean-derived pigs as models, we hypothesised that enteral feeding with plasma improves gut and immune functions in asphyxiated newborns. Near-term pig fetuses (98% gestation,) were delivered by caesarean section after 8 min umbilical cord occlusion, leading to transient birth asphyxia (ASP, n = 75) and compared with non-occluded controls (CON, n = 69). Piglets were further randomised to supplementation with/without porcine plasma (plasma, PLA/vehicle, VEH), into bovine colostrum (first 24 h) or formula (until 72 h). Compared with CON, ASP piglets took longer to achieve stable respiration and showed reduced blood pH, weight gain and survival. Independent of asphyxia, plasma supplementation reduced gut haemorrhagic lesions, permeability and inflammatory cytokines together with improved villous morphology and brush-border enzyme activities. Asphyxia reduced blood cytokine responses to ex vivo bacterial stimulation, whereas plasma supplementation ameliorated this effect. Dietary plasma supplementation improves survival, gut functions and immunity in both normal and asphyxiated newborns. The components in plasma that mediate gut-protective effects in piglets remain to be identified, but may benefit also birth-compromised newborn infants. Complicated deliveries leading to birth asphyxia, may negatively affect gut, liver and immune adaptation in the first days after birth. Using a model of birth asphyxia in caesarean-derived piglets, we show that enteral feeding with maternal plasma exerts gut maturational and immunomodulatory effects in both control and asphyxiated animals in the first days of life. The mechanisms behind the gut-protective effects of plasma are unknown, but plasma components hold potential for new oral therapies for compromised newborn infants as well as piglets.

The Effect of Vitamins on the Immune Systems of Pigs.

In modern pig farming, there are many environmental, physiological or social stresses that weaken the immune response and increase susceptibility to disease. Nutritional management has a significant impact on the efficiency of the immune system in pigs. Among the various nutrients, vitamins have been shown to have specific effects on immune system activity. However, the needs of modern genetic types are not met by the dietary recommendations for vitamins in pig diets. The present study therefore summarises the data on dietary integration with supranutritional doses of vitamins in gestating and lactating sows and post-weaning piglets in terms of the immune response. The present data highlight that high doses of dietary vitamins are an effective way to improve the immune system, antioxidant status and gut health. Further studies are needed to deepen the understanding of the role of dietary supplementation with vitamins in pigs on immune system and gut functionality.

Experience-dependent grooming microstructure alterations and gastrointestinal dysfunction in the SAPAP3 knockout mouse model of compulsive behaviour

BackgroundCompulsive- and anxiety-like behaviour can be efficiently modelled in SAPAP3 knockout (KO) mice, a preclinical model of relevance to obsessive-compulsive disorder (OCD). Although there is emerging evidence in the clinical literature of gastrointestinal dysfunction in OCD, no previous studies have investigated gut function in preclinical models of relevance to OCD. Similarly, the effects of voluntary exercise (EX) or environmental enrichment (EE) have not yet been explored in this context. MethodWe comprehensively phenotyped the SAPAP3 KO mouse model, including the assessment of grooming microstructure, anxiety- and depressive-like behaviour, and gastrointestinal function. Mice were exposed to either standard housing (SH), exercise (EX, provided by giving mice access to running wheels), or environmental enrichment (EE) for 4 weeks to investigate the effects of enriched housing conditions in this animal model relevant to OCD. FindingsOur study is the first to assess grooming microstructure, perseverative locomotor activity, and gastrointestinal function in SAPAP3 KO mice. We are also the first to report a sexually dimorphic effect of grooming in young-adult SAPAP3 KO mice; along with changes to grooming patterning and indicators of gut dysfunction, which occurred in the absence of gut dysbiosis in this model. Overall, we found no beneficial effects of voluntary exercise or environmental enrichment interventions in this mouse model; and unexpectedly, we revealed a deleterious effect of wheel-running exercise on grooming behaviour. We suspect that the detrimental effects of experimental housing in our study may be indicative of off-target effects of stress—a conclusion that warrants further investigation into the effects of chronic stress in this preclinical model of compulsive behaviour.

Rapid Microbial Profiling through Multimodal Biosensors for Transversal Analysis.

The intricate interactions between host and microbial communities hold significant implications for biology and medicine. However, traditional microbial profiling methods face limitations in processing time, measurement of absolute abundance, detection of low biomass, discrimination between live and dead cells, and functional analysis. This study introduces a rapid multimodal microbial characterization platform, Multimodal Biosensors for Transversal Analysis (MBioTA), for capturing the taxonomy, viability, and functional genes of the microbiota. The platform incorporates single cell biosensors, scalable microwell arrays, and automated image processing for rapid transversal analysis in as few as 2 h. The multimodal biosensors simultaneously characterize the taxon, viability, and functional gene expression of individual cells. By automating the image processing workflow, the single cell analysis techniques enable the quantification of bacteria with sensitivity down to 0.0075%, showcasing its capability in detecting low biomass samples. We illustrate the applicability of the MBioTA platform through the transversal analysis of the gut microbiota composition, viability, and functionality in a familial Alzheimer's disease mouse model. The effectiveness, rapid turnaround, and scalability of the MBioTA platform will facilitate its application from basic research to clinical diagnostics, potentially revolutionizing our understanding and management of diseases associated with microbe-host interactions.

Multi-Omics Analysis Reveals the Regulatory Mechanism of Different Probiotics on Growth Performance and Intestinal Health of Salmo trutta (S. trutta).

Probiotics play an important role in animal production, providing health benefits to the host by improving intestinal microbial balance. In this study, we added three different probiotics, Saccharomyces cerevisiae (SC), Bacillus licheniformis (BL), and lactic acid bacteria (LAB), and compared them with the control group (CON), to investigate the effects of probiotic supplementation on growth performance, gut microbiology, and gut flora of S. trutta. Our results showed that feeding probiotics improved the survival, growth, development, and fattening of S. trutta. Additionally, probiotic treatment causes changes in the gut probiotic community, and the gut flora microorganisms that cause significant changes vary among the probiotic treatments. However, in all three groups, the abundance of Pseudomonas, Acinetobacter, and Rhizophagus bacterial genera was similar to that in the top three comparative controls. Furthermore, differences in the composition of intestinal microbiota among feed types were directly associated with significant changes in the metabolomic landscape, including lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds. The probiotic treatment altered the gut microbiome, gut metabolome, and growth performance of S. trutta. Using a multi-omics approach, we discovered that the addition of probiotics altered the composition of gut microbiota, potentially leading to modifications in gut function and host phenotype. Overall, our results highlight the importance of probiotics as a key factor in animal health and productivity, enabling us to better evaluate the functional potential of probiotics.

Melodious tuning of microbial dynamics in biofloc, cage, and pond culturing system: a study on Pangasius pangasius fish gut microbiome.

Aquaculture, a rapidly expanding sector, meets the global surging demand for aquatic food. Pangasius, a highly valued freshwater species, has seen a significant increase in demand due to its adaptability and potential for high yields, making it a promising candidate for aquaculture in India. This study investigates the gut microbiome composition of Pangasius pangasius fish cultured in three different systems (biofloc, cage, and pond). Metagenomic DNA extraction and 16S rRNA gene-targeted sequencing were performed. Outcomes revealed distinct microbial compositions across culture types, with significant differences in species richness and diversity, specifically in the biofloc system, compared to cages and ponds. Taxonomic analysis identified prevalent phyla such as Firmicutes and Fusobacteriota, with varying abundances among culture systems. The genus-level analysis highlighted dominant genera such as Cetobacterium and WWE3. Functional profiling indicated differences in enzymatic activity and metabolic pathways, emphasizing each culture sample type's unique microbial community structures. Notably, the microbiota from BF samples exhibited significant differences and unique metabolic pathways compared to the microbiota from C and P samples, which showed greater similarity and shared several common metabolic pathways. These findings highlight substantial differences in microbial diversity across the culturing systems, reflecting the microbiota's ability to adapt to specific environments and their potential role in promoting fish growth within those environments. Overall, this study provides insights into the gut microbiome diversity and functionality in Pangasius pangasius across different aquaculture environments, contributing to a better understanding of host-microbe interactions and aquaculture management strategies.

Malaria in pregnancy: baby steps.

Malaria threatens pregnant women and their babies, particularly in Africa. This century, the number of women at risk of malaria in pregnancy has decreased globally, apart from in Africa, where it has increased. Low and sub microscopic infections are increasingly documented but remain hard to diagnose with current point-of-care tests, and their contribution to morbidity and transmission are unclear. Artemether-lumefantrine has been endorsed for treatment in first trimester, but many women attend antenatal clinics later in pregnancy, and reaching high-risk young, first-time mothers is particularly difficult. Small-for-gestational-age babies frequently result from malaria, which affects the placenta's development and its functions such as nutrient transport. Resistance to continues to increase to sulphadoxine-pyrimethamine, the mainstay of intermittent preventive treatment in pregnancy. The alternative, dihydroartemisinin-piperaquine controls malaria better, but does not improve pregnancy outcomes, suggesting that sulphadoxine-pyrimethamine may have nonmalarial effects including improving gut function or reducing dangerous inflammation. Understanding of how the malaria parasite uses the VAR2CSA protein to bind to its placental receptor is increasing, informing the search for a vaccine to prevent pregnancy malaria. Progress in several areas increases optimism that improved prevention and control of malaria in pregnancy is possible, but obstacles remain.

Muscarinic and Nitric oxide Pathway Involvement in the Intestinal Transit and Gastric Emptying delay of Salvia barrelieri Methanol Extract in Mice

This study investigated the influence of Salvia barrelieri (SBA) methanol and decocted extracts (ME and DE) on intestinal transit (IT) and gastric emptying (GE) in mice. Only the doses of ME SBA induced a strong inhibition of GE at 46.82 ± 4.34, 54.71 ± 3.29 and 48.45 ± 1.33% (P≤0.0001) for the dosages 100, 200 or 400 mg·kg-1 respectively. The extracts by themselves had no effects on intestinal movement (only a slight, non–significant increase at 400 mg·kg-1). However, blocking muscarinic receptors resulted in a decrease in IT by 10.34 and 17.53% with ME and DE extracts, respectively, compared to control. Conversely, co–administration with L–arginine (Nitric Oxide donor) significantly decreased transit (47.31 and 50.80% for ME and DE, respectively), while inhibiting Nitric Oxide Synthase (NOS) with L–Nω–Nitro–Arginine (L–NNA) had a smaller effect (12.24 and 17.24% for ME and ED, respectively). Only ME SBA extracts significantly inhibited GE (46.82–54.71% decrease across doses), mimicking atropine’s effect. DE extracts and combining ME with atropine showed no significant impact. Interestingly, L–arginine only affected emptying with DE SBA (27.8% decrease), not ME SBA. Inhibiting NOS partially blocked the effect of ME SBA. These findings suggest that ME SBA extracts primarily target GE through mechanisms involving both muscarinic and NO pathways, while DE extracts have minimal effects. This study highlights the intricate interplay of pathways in gut function and the potential influence of extract type and formulation on their effectiveness.

Effects of chronic unpredictable mild stress on gut sensation and function in male mice

Stress has been linked to the development of irritable bowel syndrome (IBS), and various methods have been explored to model IBS in combination with other stimuli. However, it remains unclear whether stress alone can induce IBS in animals. This study aimed to investigate the impact of chronic unpredictable mild stress (CUMS) on gastrointestinal sensation and function in mice and assess the potential of CUMS as a modeling approach for IBS. To evaluate the mice’s behavior, we conducted open field test, sucrose preference test and weighed the mice, revealing that CUMS indeed induced anxiety and depression in the mice and caused weight loss. Further analyses, including fecal analysis, a total gastrointestinal transport test, and a colon propulsion test, demonstrated that CUMS led to abnormal defecation and disruptions in gastrointestinal motility in the mice. Additionally, the abdominal withdrawal reflex test indicated an increase in visceral sensitivity in CUMS-exposed mice. Histological examination using hematoxylin and eosin staining revealed no significant histological alterations in the colons of CUMS-exposed mice, but it did show a minor degree of inflammatory cell infiltration. In summary, the findings suggest that CUMS can replicate IBS-like symptoms in mice, offering a novel top-down approach to modeling IBS.

Multikingdom and functional gut microbiota markers for autism spectrum disorder.

Associations between the gut microbiome and autism spectrum disorder (ASD) have been investigated although most studies have focused on the bacterial component of the microbiome. Whether gut archaea, fungi and viruses, or function of the gut microbiome, is altered in ASD is unclear. Here we performed metagenomic sequencing on faecal samples from 1,627 children (aged 1-13 years, 24.4% female) with or without ASD, with extensive phenotype data. Integrated analyses revealed that 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes and 12 metabolic pathways were altered in children with ASD. Machine learning using single-kingdom panels showed area under the curve (AUC) of 0.68 to 0.87 in differentiating children with ASD from those that are neurotypical. A panel of 31 multikingdom and functional markers showed a superior diagnostic accuracy with an AUC of 0.91, with comparable performance for males and females. Accuracy of the model was predominantly driven by the biosynthesis pathways of ubiquinol-7 or thiamine diphosphate, which were less abundant in children with ASD. Collectively, our findings highlight the potential application of multikingdom and functional gut microbiota markers as non-invasive diagnostic tools in ASD.

Effect of Lacticaseibacillus casei LC2W Supplementation on Glucose Metabolism and Gut Microbiota in Subjects at High Risk of Metabolic Syndrome: A Randomized, Double-blinded, Placebo-controlled Clinical Trial.

Metabolic syndrome (MetS) is a global epidemic complex and will cause serious metabolic comorbidities without treatment. A prevention strategy for MetS development has been proposed to modulate gut microbiota by probiotic administrationto improve intestinal dysbiosis and benefit the host. Lacticaseibacillus casei LC2W has exhibited positive effects in preventing colitis and anti-hypertension in vivo. However, the effect of L. casei LC2W on subjects at high risk of MetS is unknown. Here, a randomized, double-blinded, placebo-controlled study was conducted on 60 subjects with high risk of MetS, and the hypoglycemic and hypolipidemic activity and possible pathways of L. casei LC2W were inferred from the correlation analysis with gut microbiome composition, function, and clinical phenotypic indicators. The results showed that oral administration of L. casei LC2W could exert significant benefits on weight control, glucose and lipid metabolism, inflammatory and oxidative stress parameters, and SCFA production, as well as modulate the composition of gut microbiota. The relative abundance of Lacticaseibacillus, Bifidobacterium, Dorea, and Blautia was enriched, and their interaction with other gut microbes was strengthened by oral administration of L. casei LC2W, which was beneficial in ameliorating gut inflammation, promoting glucose and lipids degradation pathways, thus alleviated MetS. The present study confirmed the prevention effects of L. casei LC2W towards MetS from aspects of clinical outcomes and microflora modulation, providing an alternative strategy for people at high risk of MetS.Trial registration: The study was proactively registered in ClinicalTrial.gov with the registration number of ChiCTR2000031833 on April 09, 2020.

Modulation of human gut microbiota by linear and branched fructooligosaccharides in an in vitro colon model (TIM-2).

This study aimed to compare the effects of linear and branched fructooligosaccharides (FOS) extracted from chicory and grass (Lolium perenne), respectively on human microbiota composition, diversity, and metabolism. To test the effects of linear and branched FOS on human microbiota we used the artificial in vitro human colon model (TIM-2). Microbiota composition and diversity were assessed by V3-V4 16S rRNA metagenomic sequencing, followed by differential taxa abundance and alpha/beta diversity analyses. SCFA/BCFA production was evaluated by gas chromatography-mass spectrometry. As a result, branched FOS had the most beneficial effects on microbial diversity and metabolite production. Also, branched FOS significantly increased the abundance of commensal bacteria associated with maintaining healthy gut functions and controlling inflammation, such as Butyricicoccus, Erysipelotrichaceae, Phascolarctobacterium, and Sutterella. Linear FOS also significantly increased the abundance of some other commensal gut bacteria (Anaerobutyricum, Lachnospiraceae, Faecalibacterium), but there were no differences in diversity metrics compared to the control. The study revealed that branched FOS had the most beneficial effects compared to the linear FOS in vitro, concerning microbiota modulation, and metabolite production, making this a good candidate for further studies in food biotechnology.

Innovative concepts in diet therapies in disorders of gut-brain interaction.

Diet therapy in disorders of gut-brain interaction (DGBI) is rapidly advancing, with accumulating evidence to support two innovative therapies-manipulation of dietary fibers and enzyme supplementation-that target specific DGBI pathophysiology and modulate digestion. Dietary fibers escape digestion in the upper gastrointestinal tract and can influence gut function by impacting digestion, improving laxation, and interacting with the microbiota. A more nuanced understanding of different fiber types and their ability to impact gut function in highly specific ways has shown that fibers can impact distinct gut symptoms and pathophysiology. By considering their functional characteristics of bulking, gel-forming, and fermentability, restriction or supplementation of specific fibers can offer clinical value in DGBI. Similarly to fiber specificity, emerging evidence suggests that supplemental digestive enzymes may be targeted to known food triggers with consideration that enzymes are substrate specific. Limited evidence supports use of lactase to target lactose, and α-galactosidase to target galacto-oligosaccharides. Application of enzymes during manufacturing of food products may prove to be an additional strategy, although evidence is scant. Both innovative therapies may be utilized in isolation or in combination with other diet and nondiet therapies. Implementation can be guided by the principles that fiber modulation can be targeted to specific symptomology or requirement for alterations to gut function, and digestive enzymes can be targeted to known food triggers. This review aims to summarize recent literature of these two innovative concepts and provide practical suggestions for their implementation in clinical practice.

Dietary iron intake has long-term effects on the fecal metabolome and microbiome.

Iron is essential for life, but its imbalances can lead to severe health implications. Iron deficiency is the most common nutrient disorder worldwide, and iron dysregulation in early life has been found to cause long-lasting behavioral, cognitive, and neural effects. However, little is known about the effects of dietary iron on gut microbiome function and metabolism. In this study, we sought to investigate the impact of dietary iron on the fecal metabolome and microbiome by using mice fed with three diets with different iron content: an iron deficient, an iron sufficient (standard), and an iron overload diet for 7 weeks. Additionally, we sought to understand whether any observed changes would persist past the 7-week period of diet intervention. To assess this, all feeding groups were switched to a standard diet, and this feeding continued for an additional 7 weeks. Analysis of the fecal metabolome revealed that iron overload and deficiency significantly alter levels of peptides, nucleic acids, and lipids, including di- and tri-peptides containing branched-chain amino acids, inosine and guanosine, and several microbial conjugated bile acids. The observed changes in the fecal metabolome persist long after the switch back to a standard diet, with the cecal gut microbiota composition and function of each group distinct after the 7-week standard diet wash-out. Our results highlight the enduring metabolic consequences of nutritional imbalances, mediated by both the host and gut microbiome, which persist after returning to the original standard diets.

Gut microbiota modulatory capacity of fermented ketchup in a validated in vitro model of the colon

This study aimed to evaluate the effects of fermented beetroot ketchup enriched with Lactobacillus johnsonii K4 and non-fermented beetroot ketchup on pooled fecal microbiota from healthy adults in in vitro colon model. The research focused on how these products influenced the composition and functionality of the gut microbiota, as well as metabolite production, using the validated dynamic in vitro colon model, TNO Intestinal Model (TIM-2). After an initial starvation phase, a single 60 g dose of predigested and freeze-dried ketchup was introduced into the model. The potential probiotic strain Lactobacillus johnsonii K4 was added over three days. A carbohydrate mixture of standard ileal effluent medium (SIEM) served as the control. Our analysis identified 21 bacterial taxa that were significantly modulated (q-value < 0.2) when comparing ketchup samples to control samples. Notably, the ketchup samples led to an increase in butyrate-producing taxa, including Faecalibacterium, Blautia, Ruminococcaceae, Ruminiclostridium 6, and Anaerostipes. Conversely, there was a reduction in potentially pathogenic genera Desulfovibrio and Escherichia-Shigella. Distinct profiles of short-chain fatty acids (SCFA) were observed among the fermented ketchup, non-fermented ketchup, and control samples. Non-fermented ketchup resulted in higher proportions of acetate, propionate, and butyrate compared to the other interventions. This may be related to the fermentation with lactic acid bacteria in fermented samples with lower levels of substrate for SCFAs production. However, fermented ketchup sample has higher relative abundance of beneficial bacteria like Lactobacillus, Weissella and Dorea in gut microbiota. These findings suggest that beetroot ketchup, can positively influence gut microbiota composition and function, highlighting its potential benefits for human health.

Anti-diabetic effect of dicaffeoylquinic acids is associated with the modulation of gut microbiota and bile acid metabolism

IntroductionThe human gut microbiome plays a pivotal role in health and disease, notably through its interaction with bile acids (BAs). BAs, synthesized in the liver, undergo transformation by the gut microbiota upon excretion into the intestine, thus influencing host metabolism. However, the potential mechanisms of dicaffeoylquinic acids (DiCQAs) from Ilex kudingcha how to modulate lipid metabolism and inflammation via gut microbiota remain unclear. Objectives and methodsThe objectives of the present study were to investigate the regulating effects of DiCQAs on diabetes and the potential mechanisms of action. Two mice models were utilized to investigate the anti-diabetic effects of DiCQAs. Additionally, analysis of gut microbiota structure and functions was conducted concurrently with the examination of DiCQAs’ impact on gut microbiota carrying the bile salt hydrolase (BSH) gene, as well as on the enterohepatic circulation of BAs and related signaling pathways. ResultsOur findings demonstrated that DiCQAs alleviated diabetic symptoms by modulating gut microbiota carrying the BSH gene. This modulation enhanced intestinal barrier integrity, increased enterohepatic circulation of conjugated BAs, and inhibited the farnesoid X receptor-fibroblast growth factor 15 (FGF15) signaling axis in the ileum. Consequently, the protein expression of hepatic FGFR4 fibroblast growth factor receptor 4 (FGFR4) decreased, accompanied by heightened BA synthesis, reduced hepatic BA stasis, and lowered levels of hepatic and plasma cholesterol. Furthermore, DiCQAs upregulated glucolipid metabolism-related proteins in the liver and muscle, including v-akt murine thymoma viral oncogene homolog (AKT)/glycogen synthase kinase 3-beta (GSK3β) and AMP-activated protein kinase (AMPK), thereby ameliorating hyperglycemia and mitigating inflammation through the down-regulation of the MAPK signaling pathway in the diabetic group. ConclusionOur study elucidated the anti-diabetic effects and mechanism of DiCQAs from I. kudingcha, highlighting the potential of targeting gut microbiota, particularly Acetatifactor sp011959105 and Acetatifactor muris carrying the BSH gene, as a therapeutic strategy to attenuate FXR-FGF15 signaling and ameliorate diabetes.