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22 pages, 1641 KiB  
Article
Site-Specific Trafficking of Lipid and Polar Metabolites in Adipose and Muscle Tissue Reveals the Impact of Bariatric Surgery-Induced Weight Loss: A 6-Month Follow-Up Study
by Aidan Joblin-Mills, Zhanxuan E. Wu, Garth J. S. Cooper, Ivana R. Sequeira-Bisson, Jennifer L. Miles-Chan, Anne-Thea McGill, Sally D. Poppitt and Karl Fraser
Metabolites 2025, 15(8), 525; https://doi.org/10.3390/metabo15080525 - 2 Aug 2025
Viewed by 233
Abstract
Background: The causation of type 2 diabetes remains under debate, but evidence supports both abdominal lipid and ectopic lipid overspill into tissues including muscle as key. How these depots differentially alter cardiometabolic profile and change during body weight and fat loss is not [...] Read more.
Background: The causation of type 2 diabetes remains under debate, but evidence supports both abdominal lipid and ectopic lipid overspill into tissues including muscle as key. How these depots differentially alter cardiometabolic profile and change during body weight and fat loss is not known. Methods: Women with obesity scheduled to undergo bariatric surgery were assessed at baseline (BL, n = 28) and at 6-month follow-up (6m_FU, n = 26) after weight loss. Fasting plasma (Pla), subcutaneous thigh adipose (STA), subcutaneous abdominal adipose, (SAA), and thigh vastus lateralis muscle (VLM) samples were collected at BL through surgery and at 6m_FU using needle biopsy. An untargeted liquid chromatography mass spectrometry metabolomics platform was used. Pla and tissue-specific lipid and polar metabolite profiles were modelled as changes from BL and 6m_FU. Results: There was significant body weight (−24.5 kg) loss at 6m_FU (p < 0.05). BL vs. 6m_FU tissue metabolomics profiles showed the largest difference in lipid profiles in SAA tissue in response to surgery. Conversely, polar metabolites were more susceptible to change in STA and VLM. In Pla samples, both lipid and polar metabolite profiles showed significant differences between timepoints. Jaccard–Tanimoto coefficient t-tests identified a sub-group of gut microbiome and dietary-derived omega-3-fatty-acid-containing lipid species and core energy metabolism and adipose catabolism-associated polar metabolites that are trafficked between sample types in response to bariatric surgery. Conclusions: In this first report on channelling of lipids and polar metabolites to alternative tissues in bariatric-induced weight loss, adaptive shuttling of small molecules was identified, further promoting adipose processing and highlighting the dynamic and coordinated nature of post-surgical metabolic regulation. Full article
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11 pages, 827 KiB  
Study Protocol
The Effect of Faecal Microbiota Transplantation on Cognitive Function in Cognitively Healthy Adults with Irritable Bowel Syndrome: Protocol for a Randomised, Placebo-Controlled, Double-Blinded Pilot Study
by Sara Alaeddin, Yanna Ko, Genevieve Z. Steiner-Lim, Slade O. Jensen, Tara L. Roberts and Vincent Ho
Methods Protoc. 2025, 8(4), 83; https://doi.org/10.3390/mps8040083 (registering DOI) - 1 Aug 2025
Viewed by 257
Abstract
Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota–gut–brain axis. Altering gut microbial composition may influence cognitive function, but this has not been tested in cognitively healthy adults. This randomised, double-blinded, placebo-controlled pilot trial investigates [...] Read more.
Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota–gut–brain axis. Altering gut microbial composition may influence cognitive function, but this has not been tested in cognitively healthy adults. This randomised, double-blinded, placebo-controlled pilot trial investigates whether FMT is feasible and improves cognition in adults with irritable bowel syndrome (IBS). Participants receive a single dose of FMT or placebo via rectal retention enema. Cognitive performance is the primary outcome, assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Secondary outcomes include IBS symptom severity and mood. Tertiary outcomes include microbiome composition and plasma biomarkers related to inflammation, short-chain fatty acids, and tryptophan metabolism. Outcomes are assessed at baseline and at one, three, six, and twelve months following treatment. We hypothesise that FMT will lead to greater improvements in cognitive performance than placebo, with benefits extending beyond practice effects, emerging at one month and persisting in the long term. The findings will contribute to evaluating the safety and efficacy of FMT and enhance our understanding of gut–brain interactions. Full article
(This article belongs to the Section Public Health Research)
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19 pages, 2052 KiB  
Article
Effects of Time-Restricted Eating (Early and Late) Combined with Energy Restriction vs. Energy Restriction Alone on the Gut Microbiome in Adults with Obesity
by Bernarda Habe, Tanja Črešnovar, Matjaž Hladnik, Jure Pražnikar, Saša Kenig, Dunja Bandelj, Nina Mohorko, Ana Petelin and Zala Jenko Pražnikar
Nutrients 2025, 17(14), 2284; https://doi.org/10.3390/nu17142284 - 10 Jul 2025
Viewed by 1444
Abstract
Background: Early time-restricted eating combined with energy restriction (eTRE + ER) has been shown to reduce fat mass, diastolic blood pressure (DBP) and fasting glucose more effectively than late TRE with energy restriction (lTRE + ER) or energy restriction (ER) alone. Given the [...] Read more.
Background: Early time-restricted eating combined with energy restriction (eTRE + ER) has been shown to reduce fat mass, diastolic blood pressure (DBP) and fasting glucose more effectively than late TRE with energy restriction (lTRE + ER) or energy restriction (ER) alone. Given the gut microbiome’s sensitivity to circadian rhythms, we examined whether adding TRE, particularly eTRE, to ER alters gut microbiota composition beyond ER alone, and whether such effects persist during follow-up. Methods: We analysed anthropometric, biochemical and gut microbiome data from 76 participants at baseline and after a 3-month intervention (eTRE + ER: n = 33; lTRE + ER: n = 23; ER: n = 20). Follow-up microbiome data 6-months after the end of intervention were available for 43 participants. Gut microbiota composition was assessed via 16S rRNA gene sequencing of stool samples. Results: No significant between-group differences in beta diversity were observed over time. However, changes in alpha diversity differed significantly across groups at the end of the intervention (Shannon: F = 5.72, p < 0.001; Simpson: F = 6.72, p < 0.001; Richness: F = 3.99, p = 0.01) and at follow-up (Richness: F = 3.77, p = 0.02). lTRE + ER led to the greatest reductions in diversity post intervention, while ER was least favourable during follow-up. Although no significant between-group differences were observed at the phylum level either at the end of the intervention or during follow-up, only the eTRE + ER group exhibited a significant decrease in Bacillota and an increase in Bacteroidota during follow-up. At the genus level, differential abundance analysis revealed significant shifts in taxa such as Faecalibacterium, Subdoligranulum, and other genera within the Ruminococcaceae and Oscillospiraceae families. In the eTRE + ER, Faecalibacterium and Subdoligranulum increased, while in other groups decreased. Notably, the changes in Faecalibacterium were negatively correlated with fasting glucose, while the increase in Subdoligranulum was inversely associated with DBP; however, both associations were weak in strength. Conclusions: eTRE + ER may promote beneficial, lasting shifts in the gut microbiome associated with improved metabolic outcomes. These results support further research into personalized TRE strategies for treatment of obesity. Full article
(This article belongs to the Section Nutrition and Obesity)
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17 pages, 1235 KiB  
Communication
An Indole-Rich Postbiotic Reduces Itching in Dogs: A Randomized, Double-Blinded Placebo-Controlled Study
by Aylesse Sordillo, Jonna Heldrich, Raphaël Turcotte and Ravi U. Sheth
Animals 2025, 15(14), 2019; https://doi.org/10.3390/ani15142019 - 9 Jul 2025
Viewed by 1118
Abstract
Many dogs suffer from pruritus, which is commonly caused by atopic dermatitis and associated with skin inflammation. The immune system and inflammatory response, and in particular the gut–skin axis, are central to the pathogenesis of atopic dermatitis. Managing atopic dermatitis involves complex, iterative [...] Read more.
Many dogs suffer from pruritus, which is commonly caused by atopic dermatitis and associated with skin inflammation. The immune system and inflammatory response, and in particular the gut–skin axis, are central to the pathogenesis of atopic dermatitis. Managing atopic dermatitis involves complex, iterative treatment plans; early strategies supporting gut–skin health are needed to prevent elevated itching from progressing toward a disease condition requiring drug therapy. This double-blind, placebo-controlled, randomized trial evaluated the ability of a novel, indole-rich canine immune health postbiotic (CIHP) to reduce itching and promote a healthy gut microbiome in dogs with subclinical, but elevated itching behavior. Thirty dogs were stratified into two groups based on baseline scratching frequency, receiving either CIHP or placebo as a powder topper for 28 days. Canine itching was evaluated through accelerometer-based tracking and the Pruritus Visual Analog Scale (PVAS) score on Days 0, 7, 14, 21, and 28. Skin and coat health was assessed on Days 0, 14, and 28, and the gut microbiome was sequenced from fecal samples on Days 0 and 28. CIHP reduced scratching by 20% relative to the baseline (p = 0.032) and PVAS score by 27% compared to the placebo (p = 0.02). CIHP improved skin and coat quality compared to the placebo at Day 14 (p = 0.01) and increased Shannon diversity by 4.6% (p = 0.043), shifting gut microbiome composition. These findings validate this postbiotic’s ability to reduce itching in dogs with subclinical, but elevated itching behavior, provide evidence of promoting a healthy gut–skin axis, and suggest potential as an early intervention in the context of pruritic conditions, as well as for broader immune-related benefits. Full article
(This article belongs to the Section Veterinary Clinical Studies)
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28 pages, 7091 KiB  
Article
Dynamic Microbiome Responses to Structurally Diverse Anthocyanin-Rich Foods in a Western Diet Context
by Mohammed F. Almatani, Giovanni Rompato, Eliza C. Stewart, Marcus Hayden, Jeremy Case, Samuel Rice, Korry J. Hintze and Abby D. Benninghoff
Nutrients 2025, 17(13), 2201; https://doi.org/10.3390/nu17132201 - 1 Jul 2025
Cited by 1 | Viewed by 500
Abstract
Background/Objectives: Anthocyanin (ACN)-rich foods are known to influence the gut microbiota composition, but the temporal dynamics and structural specificity of these effects remain poorly understood. This study investigated how distinct ACN-rich fruit supplements impact the gut microbiome over time in the context of [...] Read more.
Background/Objectives: Anthocyanin (ACN)-rich foods are known to influence the gut microbiota composition, but the temporal dynamics and structural specificity of these effects remain poorly understood. This study investigated how distinct ACN-rich fruit supplements impact the gut microbiome over time in the context of a Western-style diet. We hypothesized that ACN-induced microbial shifts would occur rapidly, differ by ACN source, and require continued intake to persist. Methods: C57BL/6J mice were fed the total Western diet (TWD) supplemented with freeze-dried powders from bilberry (BB), tart cherry (TC), chokeberry (CB), elderberry (EB), black currant (BC), or black raspberry (BRB) for 0, 1, 3, or 7 days. Cocoa polyphenols (CPs) were included as a comparator with a distinct polyphenol profile. Fecal microbiota were collected at 0, 1, 3, and 7 days post exposure and analyzed by 16S rRNA sequencing. Results: ACN-rich supplements induced rapid microbial shifts detectable within one day of exposure. However, most changes reverted toward the baseline within days of supplement withdrawal, indicating limited persistence. Among the ACNs, BRB produced the most sustained microbiome alterations. Microbial responses varied by ACN source, suggesting that differences in glycoside and aglycone structures influence the community composition. Conclusions: ACN-rich foods can induce rapid but largely transient alterations in the gut microbiome, with variability linked to the polyphenol structure. These findings highlight the ecological sensitivity of the microbiome to specific dietary components and underscore the importance of sustained intake for maintaining microbial shifts. Full article
(This article belongs to the Special Issue Dietary Patterns and Gut Microbiota)
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10 pages, 847 KiB  
Article
Impact of a 12-Week Hypocaloric Weight Loss Diet with Mixed Tree Nuts vs. Pretzels on Trimethylamine-N-Oxide (TMAO) Levels in Overweight Adults
by Onkei Lei, Jieping Yang, Hannah H. Kang and Zhaoping Li
Nutrients 2025, 17(13), 2137; https://doi.org/10.3390/nu17132137 - 27 Jun 2025
Viewed by 541
Abstract
Trimethylamine N-oxide (TMAO), a gut microbiome metabolite linked to cardiovascular health, can be influenced by dietary factors like choline intake and diet quality. This study compared the effects of mixed tree nuts (MTNs) and pretzels, as part of a 12-week hypocaloric weight loss [...] Read more.
Trimethylamine N-oxide (TMAO), a gut microbiome metabolite linked to cardiovascular health, can be influenced by dietary factors like choline intake and diet quality. This study compared the effects of mixed tree nuts (MTNs) and pretzels, as part of a 12-week hypocaloric weight loss diet, on TMAO levels and identified dietary predictors. Methods: Plasma samples from 95 overweight individuals consuming either 1.5 oz. of mixed tree nuts (MTNs, n = 56) or isocaloric pretzels (n = 39) daily for 12 weeks were analyzed. Nutritional data were collected at baseline and week 12 through dietary recall using the Automated Self-Administered 24 h Dietary Assessment Tool (ASA24), and the overall diet quality was assessed via the Healthy Eating Index (HEI) score. TMAO levels were determined and analyzed using linear mixed-effect models, adjusting for covariates. Wilcoxon signed-rank tests compared baseline and week 12 TMAO and weight. Multiple linear regression identified baseline predictors of TMAO. Results: Baseline demographics, anthropometric measures, HEI scores, and dietary choline intake were similar between the MTN and pretzel groups. A significant positive association was observed between baseline dietary choline and plasma TMAO levels (p = 0.012). The 12-week hypocaloric diet led to significant weight reduction in both groups (p < 0.01), but the magnitude of weight loss did not differ significantly between the MTN (−3.47 lbs) and pretzel (−4.25 lbs) groups (p = 0.18). Plasma TMAO levels decreased significantly in both groups (p < 0.01), but the between-group difference in reduction was not significant. (MTNs: −0.34 vs. pretzels: −0.37; p = 0.43). HEI scores and dietary choline intake remained unchanged, with no significant time–intervention interaction. Participants with low baseline HEI scores (≤53.72) had a more pronounced reduction in TMAO levels in the MTN group compared to the pretzel group (MTN: −0.54 vs. pretzel: −0.23; p = 0.045) over 12 weeks, despite similar weight loss. This difference was not observed in participants with higher HEI scores. Conclusions: The 12-week hypocaloric diet reduced body weight and plasma TMAO levels similarly in both MTN and pretzel groups. Participants with lower dietary quality saw a greater reduction in TMAO levels in the MTN group, suggesting MTNs may better modulate TMAO levels, especially for those with poorer baseline diets. Full article
(This article belongs to the Special Issue Impact of Optimized Nutritional Strategies on Weight Control)
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29 pages, 2166 KiB  
Article
Characterizing Gene-Level Adaptations in the Gut Microbiome During Viral Infections: The Role of a Fucoidan-Rich Extract
by Gissel García, Josanne Soto, Carmen Valenzuela and Raul De Jesús Cano
Genes 2025, 16(7), 740; https://doi.org/10.3390/genes16070740 - 26 Jun 2025
Viewed by 555
Abstract
Background/Objectives: This study aimed to examine the effects of a Fucoidan-rich extract from Saccharina latissima (SLE-F) on differential gut microbiota composition, intestinal inflammation status, and microbial functional gene expression in participants infected with Dengue or Oropouche virus at the Hermanos Ameijeiras Hospital in [...] Read more.
Background/Objectives: This study aimed to examine the effects of a Fucoidan-rich extract from Saccharina latissima (SLE-F) on differential gut microbiota composition, intestinal inflammation status, and microbial functional gene expression in participants infected with Dengue or Oropouche virus at the Hermanos Ameijeiras Hospital in Havana, Cuba. Methods: Fecal samples were collected at baseline, day 28, and day 90 from 90 healthy adults, some of whom contracted the virus during the study period. Functional gene analysis was conducted using two approaches—the Kruskal–Wallis H test and linear discriminant analysis effect size—applied to ortholog-level data normalized by read count and gene copy number. Results: Infected participants exhibited significantly lower Lachnospiraceae-to-Enterobacteriaceae (LE) ratios, indicating increased intestinal inflammation. High-dose SLE-F treatment led to a significant reduction in the LE ratio (p = 0.006), suggesting a strong anti-inflammatory effect. Microbiome analysis revealed a shift from dysbiosis to a more balanced composition by the end of the study, characterized by increased abundances of Akkermansia muciniphila, Bifidobacterium adolescentis, and B. longum, along with decreased pro-inflammatory taxa such as Fusobacterium. Conclusions: Genetic analysis provided distinct yet complementary insights into the microbiome’s functional responses to infection and therapeutic modulation by Fucoidan. These findings highlight the therapeutic potential of high-dose Fucoidan in reducing gut inflammation and promoting microbiome recovery following viral infections. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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12 pages, 732 KiB  
Systematic Review
Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review
by Ielmina Domilescu, Bogdan Miutescu, Florin George Horhat, Alina Popescu, Camelia Nica, Ana Maria Ghiuchici, Eyad Gadour, Ioan Sîrbu and Delia Hutanu
Metabolites 2025, 15(6), 412; https://doi.org/10.3390/metabo15060412 - 18 Jun 2025
Viewed by 550
Abstract
Background and Objectives: Rectal cancer management increasingly relies on watch-and-wait strategies after neoadjuvant chemoradiotherapy (nCRT). Accurate, non-invasive prediction of pathological complete response (pCR) remains elusive. Emerging evidence suggests that gut-microbiome composition modulates radio-chemosensitivity. We systematically reviewed primary studies that correlated baseline or on-treatment [...] Read more.
Background and Objectives: Rectal cancer management increasingly relies on watch-and-wait strategies after neoadjuvant chemoradiotherapy (nCRT). Accurate, non-invasive prediction of pathological complete response (pCR) remains elusive. Emerging evidence suggests that gut-microbiome composition modulates radio-chemosensitivity. We systematically reviewed primary studies that correlated baseline or on-treatment gut-microbiome features with nCRT response in locally advanced rectal cancer (LARC). Methods: MEDLINE, Embase and PubMed were searched from inception to 30 April 2025. Eligibility required (i) prospective or retrospective human studies of LARC, (ii) faecal or mucosal microbiome profiling by 16S, metagenomics, or metatranscriptomics, and (iii) response assessment using tumour-regression grade or pCR. Narrative synthesis and random-effects proportion meta-analysis were performed where data were homogeneous. Results: Twelve studies (n = 1354 unique patients, median sample = 73, range 22–735) met inclusion. Four independent machine-learning models achieved an Area Under the Receiver Operating Characteristic curve AUROC ≥ 0.85 for pCR prediction. Consistently enriched taxa in responders included Lachnospiraceae bacterium, Blautia wexlerae, Roseburia spp., and Intestinimonas butyriciproducens. Non-responders showed over-representation of Fusobacterium nucleatum, Bacteroides fragilis, and Prevotella spp. Two studies linked butyrate-producing modules to radiosensitivity, whereas nucleotide-biosynthesis pathways conferred resistance. Pooled pCR rate in patients with a “butyrate-rich” baseline profile was 44% (95% CI 35–54) versus 21% (95% CI 15–29) in controls (I2 = 18%). Conclusions: Despite heterogeneity, convergent functional and taxonomic signals underpin a microbiome-based radiosensitivity axis in LARC. Multi-centre validation cohorts and intervention trials manipulating these taxa, such as prebiotics or live-biotherapeutics, are warranted before clinical deployment. Full article
(This article belongs to the Special Issue Advances in Gut Microbiome Metabolomics)
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12 pages, 1094 KiB  
Article
Non-Invasive Analyses of Altered Schaedler Flora in C57Bl/6J and Balb/c Mice to Monitor Hygiene Status of a Housing Facility
by Rebecca Nistelberger, Patrizia Gibler, Lisa Barones, Arno Absenger, Julia B. Kral-Pointner, Manuel Salzmann, Boris Hartmann, Bruno K. Podesser, Phillip J. Hohensinner and Roberto Plasenzotti
Animals 2025, 15(12), 1725; https://doi.org/10.3390/ani15121725 - 11 Jun 2025
Viewed by 683
Abstract
The composition of the gut microbiome, defined by environmental factors, significantly affects research outcomes, with variations observed across animal facilities. Efforts to standardize led to the definition of the ‘Altered Schaedler flora’ (ASF), comprising eight bacterial groups. Our data highlights the variability of [...] Read more.
The composition of the gut microbiome, defined by environmental factors, significantly affects research outcomes, with variations observed across animal facilities. Efforts to standardize led to the definition of the ‘Altered Schaedler flora’ (ASF), comprising eight bacterial groups. Our data highlights the variability of ASF under pathogen contact. Feces from two wild-type strains (C57Bl/6J and Balb/c mice) with and without proven infection was collected in two different animal facilities and analyzed. The data show a significant difference in the quantity (either reduction or increase) of the eight ASF bacterial groups when comparing infected and non-infected mice across different housing areas (SPF-specific pathogen-free, quarantine, and conventional-experimental areas) within a facility, as well as in comparison to another facility. Furthermore, strain-specific differences are also evident, with certain ASF groups showing a reduction in quantity at one facility but an increase at the other, comparing the same housing area. Comparative studies across facilities confirmed the necessity of baseline determination for accurate ASF analysis. Performing ASF analysis, facilitated by in-house qPCR (quantitative polymerase chain reaction) kits, offers prompt and precise microbiome profiling, enhancing experimental accuracy and health monitoring in animal research settings. Full article
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29 pages, 1355 KiB  
Review
The Effects of Fecal Microbial Transplantation on the Symptoms in Autism Spectrum Disorder, Gut Microbiota and Metabolites: A Scoping Review
by Ignazio Maniscalco, Piotr Bartochowski, Vittoria Priori, Sidonia Paula Iancau, Michele De Francesco, Marco Innamorati, Natalia Jagodzinska, Giancarlo Giupponi, Luca Masucci, Andreas Conca and Magdalena Mroczek
Microorganisms 2025, 13(6), 1290; https://doi.org/10.3390/microorganisms13061290 - 31 May 2025
Viewed by 990
Abstract
The bilateral interaction between the brain and the gut has recently been on the spectrum of researchers’ interests, including complex neural, endocrinological, and immunological signaling pathways. The first case reports and clinical studies have already reported that delivering microbes through fecal microbial transplantation [...] Read more.
The bilateral interaction between the brain and the gut has recently been on the spectrum of researchers’ interests, including complex neural, endocrinological, and immunological signaling pathways. The first case reports and clinical studies have already reported that delivering microbes through fecal microbial transplantation (FMT) may alleviate symptoms of psychiatric disorders. Therefore, modifying the gut microbiota through FMT holds promise as a potential treatment for psychiatric diseases. This scoping review assessed studies from PubMed related to FMT in autism spectrum disorder and attention deficit hyperactivity disorder. The evaluation included nine clinical studies and case reports. The beneficial and persistent effect on the autism spectrum disorder (ASD) symptoms has been reported. Also, an increased microflora diversity and altered levels of neurometabolites in serum were identified, albeit with a tendency to return to baseline over time. The microbiome–gut–brain axis could provide new targets for preventing and treating psychiatric disorders. However, a recent large randomized clinical trial has shed light on the previously collected data and suggested a possible contribution of the placebo effect. This highlights the necessity of large randomized double-blind studies to reliably assess the effect of FMT in ASD. Full article
(This article belongs to the Special Issue Effects of Gut Microbiota on Human Health and Disease, 2nd Edition)
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26 pages, 12843 KiB  
Article
Prebiotic-like Effects of Proanthocyanidin-Rich Aronia Extract Supplementation on Gut Microbiota Composition and Function in the Twin-M-SHIME® Model
by Blanca Elizabeth Ruiz-Álvarez, Valentina Cattero and Yves Desjardins
Pharmaceuticals 2025, 18(6), 793; https://doi.org/10.3390/ph18060793 - 25 May 2025
Cited by 1 | Viewed by 1604
Abstract
Background: Phenolic compounds, particularly anthocyanins and proanthocyanidins (PACs), are poorly absorbed in the upper digestive tract and reach the colon largely intact, where they may influence gut microbiota (GM) composition and, in turn, impact host health. We hypothesized that a PAC-rich aronia [...] Read more.
Background: Phenolic compounds, particularly anthocyanins and proanthocyanidins (PACs), are poorly absorbed in the upper digestive tract and reach the colon largely intact, where they may influence gut microbiota (GM) composition and, in turn, impact host health. We hypothesized that a PAC-rich aronia extract would beneficially modulate the GM, promote the growth of health-associated bacteria, and enhance short-chain fatty acid (SCFA) production across different colon sections, with partial reversion effects after supplementation ends. Methods: The Twin-M-SHIME® system was used to simulate the digestion and colonic fermentation in two donors with contrasting microbiota profiles. The experimental design included four phases: stabilization (14 days), control (7 days), treatment with 500 mg/day PAC-rich aronia extract (21 days), and wash-out (10 days). SCFA production was monitored, and changes in microbiome composition were assessed using 16S rRNA gene sequencing. Results: PAC-rich aronia extract significantly modulated SCFA levels, increasing butyrate and reducing acetate, with some inter-donor variability. SCFA concentrations tended to return to baseline after the wash-out (WO) period. Metagenomic analysis revealed a decrease in Collinsella, Sutterella, Selenomonas, and Parabacteroides—genera linked to low-fiber diets and gut inflammation—while promoting Proteobacteria (e.g., Escherichia-Shigella, Klebsiella) and butyrate-associated Firmicutes such as Lactiplantibacillus. Although some microbial shifts partially reverted during the wash-out (e.g., Akkermansia, Bacteroides, and Bifidobacterium), other changes persisted. Conclusions: These findings suggest that PAC-rich aronia extract beneficially modulates GM and SCFA production, but continuous intake may be necessary to maintain these effects over time. Full article
(This article belongs to the Section Biopharmaceuticals)
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16 pages, 705 KiB  
Article
Prognostic Value of a Multivariate Gut Microbiome Model for Progression from Normal Cognition to Mild Cognitive Impairment Within 4 Years
by Anne Bauch, Julia Baur, Iris Honold, Matthias Willmann, Greta Louise Weber, Stephan Müller, Sebastian Sodenkamp, Silke Peter, Ulrich Schoppmeier and Christoph Laske
Int. J. Mol. Sci. 2025, 26(10), 4735; https://doi.org/10.3390/ijms26104735 - 15 May 2025
Viewed by 544
Abstract
Little is known about the dysbiosis of the gut microbiome in patients with mild cognitive impairment (MCI) potentially at risk for the development of Alzheimer’s disease (AD). So far, only cross-sectional differences and not longitudinal changes and their prognostic significance have been in [...] Read more.
Little is known about the dysbiosis of the gut microbiome in patients with mild cognitive impairment (MCI) potentially at risk for the development of Alzheimer’s disease (AD). So far, only cross-sectional differences and not longitudinal changes and their prognostic significance have been in the scope of research in MCI. Therefore, we investigated the ability of longitudinal taxonomic and functional gut microbiome data from 100 healthy controls (HC) to predict the progression from normal cognition to MCI over a 4-year follow-up period (4yFU). Logistic regression models were built with baseline features that best discriminated between the two groups using an ANOVA-type statistical analysis. The best model for the discrimination of MCI converters was based on functional data using Gene Ontology (GO), which included 14 features. This model achieved an area under the receiver operating characteristic curve (AUROC) of 0.84 at baseline, 0.78 at the 1-year follow-up (1yFU), and 0.75 at 4yFU. This functional model outperformed the taxonomic model, which included 38 genera features, in terms of descriptive performance and showed comparable efficacy to combined analyses integrating functional, taxonomic, and clinical characteristics. Thus, gut microbiome algorithms have the potential to predict MCI conversion in HCs over a 4-year period, offering a promising innovative supplement for early AD identification. Full article
(This article belongs to the Special Issue Molecular Research in Human Microbiome 2.0)
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17 pages, 3855 KiB  
Article
Reduced Sulfur Diet Reshapes the Microbiome and Metabolome in Mild–Moderate Ulcerative Colitis
by Jiayu Ye, Maitreyi Raman, Lorian M. Taylor, Munazza Yousuf, Remo Panaccione, Christian Turbide, Sidhartha R. Sinha and Natasha Haskey
Int. J. Mol. Sci. 2025, 26(10), 4596; https://doi.org/10.3390/ijms26104596 - 11 May 2025
Viewed by 1169
Abstract
This pilot study investigated the effects of a reduced sulfur (RS) diet on the gut microbiome composition and fecal metabolome in individuals with remitted or active ulcerative colitis (UC). Thirteen participants maintained their habitual diet (control), while nine followed an RS diet for [...] Read more.
This pilot study investigated the effects of a reduced sulfur (RS) diet on the gut microbiome composition and fecal metabolome in individuals with remitted or active ulcerative colitis (UC). Thirteen participants maintained their habitual diet (control), while nine followed an RS diet for eight weeks (Wk8). Stool and plasma samples were collected at the baseline and Wk8. The sulfur intake decreased in the RS group (−28 g/1000 kcal) versus the control group (−1.7 g/1000 kcal; p < 0.001). The RS group exhibited a significant decrease in lipopolysaccharide-binding protein (−5280 ng/mL), while these levels increased in the control group (620 ng/mL; p < 0.05). The microbiome analysis showed an increased alpha diversity at Wk8 (p < 0.01), suggesting a microbial shift with a RS intake. The metabolic alterations indicated enhanced nitrogen disposal (increased uric acid, methyluric acid, N-acetyl-L-glutamate) and a higher energy demand (elevated ubiquinol and glucose-pyruvate). The RS diet increased beneficial microbes Collinsella stercoris, Asaccharobacter celatus, and Alistipes finegoldii, while decreasing pathobionts Eggerthella lenta and Romboutsia ilealis. Methyluric acid correlated positively with C. stercoris (β = 0.70) and negatively with E. lenta (β = −0.77) suggesting these microbes utilized this metabolite and influenced the microbiome composition. In conclusion, a RS diet promoted microbial diversity, metabolic adaptations, and reduced inflammation, highlighting its potential as a novel strategy for UC management. Full article
(This article belongs to the Special Issue Inflammatory Bowel Disease and Microbiome)
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18 pages, 2348 KiB  
Article
Effects of Metronidazole on the Fecal Microbiota, Fecal Metabolites, and Serum Metabolites of Healthy Adult Cats
by Sara E. Martini, Teresa Schmidt, Wenyi Huang, Amanda B. Blake, João P. Cavasin, Jan S. Suchodolski and Kelly S. Swanson
Pets 2025, 2(2), 19; https://doi.org/10.3390/pets2020019 - 28 Apr 2025
Viewed by 2687
Abstract
Antibiotics are commonly used to aid in the remission of gastrointestinal diseases, but usage may lead to prolonged dysbiosis. The objective of this study was to evaluate the effects of metronidazole on fecal microbiota, fecal metabolites, and serum bile acids and uremic toxins [...] Read more.
Antibiotics are commonly used to aid in the remission of gastrointestinal diseases, but usage may lead to prolonged dysbiosis. The objective of this study was to evaluate the effects of metronidazole on fecal microbiota, fecal metabolites, and serum bile acids and uremic toxins of healthy adult cats. Twelve healthy adult cats (4.7 ± 0.4 yr) received metronidazole (20 mg/kg BW PO BID) for 14 days (day 0–14) and were monitored during a 28-day recovery period (day 15–42). Fecal and blood samples were collected at baseline (day 0), after metronidazole (day 14), and weekly during recovery (on days 21, 28, 35, and 42). Fecal samples were analyzed for microbiota and bacterial metabolites. Serum samples were analyzed for bile acids and uremic toxins. Metronidazole increased dysbiosis index and fecal lactate concentrations (p < 0.0001) and decreased fecal propionate, butyrate, and secondary bile acid concentrations (p < 0.0001) for up to 28 days. Prolonged dysbiosis and Peptacetobacter (Clostridium) hiranonis reductions were observed in 10/12 (83%) cats. Serum uremic toxins were also reduced (p < 0.0001) after metronidazole administration. The observed changes after metronidazole administration illustrate how changes in the gut microbiome alter microbial metabolism and its relation to host dysmetabolism. In conclusion, metronidazole is a potent antibiotic with persistent effects observed in the microbiome and metabolome, even up to one month after administration. Full article
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Article
The Influence of an AI-Driven Personalized Nutrition Program on the Human Gut Microbiome and Its Health Implications
by Konstantinos Rouskas, Mary Guela, Marianna Pantoura, Ioannis Pagkalos, Maria Hassapidou, Elena Lalama, Andreas F. H. Pfeiffer, Elise Decorte, Veronique Cornelissen, Saskia Wilson-Barnes, Kathryn Hart, Eugenio Mantovani, Sofia Balula Dias, Leontios Hadjileontiadis, Lazaros P. Gymnopoulos, Kosmas Dimitropoulos and Anagnostis Argiriou
Nutrients 2025, 17(7), 1260; https://doi.org/10.3390/nu17071260 - 3 Apr 2025
Cited by 1 | Viewed by 6116
Abstract
Background/Objectives: Personalized nutrition programs enhanced with artificial intelligence (AI)-based tools hold promising potential for the development of healthy and sustainable diets and for disease prevention. This study aimed to explore the impact of an AI-based personalized nutrition program on the gut microbiome of [...] Read more.
Background/Objectives: Personalized nutrition programs enhanced with artificial intelligence (AI)-based tools hold promising potential for the development of healthy and sustainable diets and for disease prevention. This study aimed to explore the impact of an AI-based personalized nutrition program on the gut microbiome of healthy individuals. Methods: An intervention using an AI-based mobile application for personalized nutrition was applied for six weeks. Fecal and blood samples from 29 healthy participants (females 52%, mean age 35 years) were collected at baseline and at six weeks. Gut microbiome through 16s ribosomal RNA (rRNA) amplicon sequencing, anthropometric and biochemical data were analyzed at both timepoints. Dietary assessment was performed using food frequency questionnaires. Results: A significant increase in richness (Chao1, 220.4 ± 58.5 vs. 241.5 ± 60.2, p = 0.024) and diversity (Faith’s phylogenetic diversity, 15.5 ± 3.3 vs. 17.3 ± 2.8, p = 0.0001) was found from pre- to post-intervention. Following the intervention, the relative abundance of genera associated with the reduction in cholesterol and heart disease risk (e.g., Eubacterium coprostanoligenes group and Oscillobacter) was significantly increased, while the abundance of inflammation-associated genera (e.g., Eubacterium ruminantium group and Gastranaerophilales) was decreased. Alterations in the abundance of several butyrate-producing genera were also found (e.g., increase in Faecalibacterium, decrease in Bifidobacterium). Further, a decrease in carbohydrate (272.2 ± 97.7 vs. 222.9 ± 80.5, p = 0.003) and protein (113.6 ± 38.8 vs. 98.6 ± 32.4, p = 0.011) intake, as well as a reduction in waist circumference (78.4 ± 12.1 vs. 77.2 ± 11.2, p = 0.023), was also seen. Changes in the abundance of Oscillospiraceae_UCG_002 and Lachnospiraceae_UCG_004 were positively associated with changes in olive oil intake (Rho = 0.57, p = 0.001) and levels of triglycerides (Rho = 0.56, p = 0.001). Conclusions: This study highlights the potential for an AI-based personalized nutrition program to influence the gut microbiome. More research is now needed to establish the use of gut microbiome-informed strategies for personalized nutrition. Full article
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