Background:People with HIV (PWH), despite effective antiretroviral therapy (ART), experience disrupted intestinal homeostasis characterized by microbial dysbiosis and impaired intestinal barrier integrity, which contribute to chronic inflammation and aging-associated comorbidities. However, tractable mechanisms contributing to this dysfunction remain poorly defined. Objective:To determine whether acquired loss of intestinal α1,2-fucose, a host-derived intrinsic prebiotic glycan that supports colonization by short-chain fatty acid (SCFA)-producing bacteria essential for intestinal barrier integrity, contributes to microbiome disruption, impaired epithelial resilience, inflammation, and biological aging in PWH. Design:Ileal and colonic biopsies, isolated crypts, stool, and blood from PWH on ART and controls underwent multi-omic analyses. Findings were mechanistically interrogated using stool anaerobic fermentation assays and 3D intestinal organoid models of stress-mediated epithelial disruption. Results:In intestinal tissues, PWH exhibited reduced α1,2-fucosylation and increased senescence-associated expression of the fucose-degrading enzyme α-L-fucosidase. Lower α1,2-fucose tracked with depletion of SCFA-producing bacteria, increased inflammation, and premature biological aging. In anaerobic fermentations, stool from PWH produced fewer SCFAs than controls, whereas supplementation with the human-milk-oligosaccharide-derived α1,2-fucose donor 2'-fucosyllactose restored SCFA production and improved intestinal organoid resilience to stress-mediated disruption. Conclusion:These findings identify acquired loss of intestinal α1,2-fucose as a modifiable host-microbiome mechanism linking epithelial senescence, microbial metabolic dysfunction, impaired barrier resilience, inflammation, and biological aging in treated HIV infection.

We hypothesize that intestinal microbiome dysbiosis may contribute to Parkinson's disease (PD) pathogenesis. Our prior proof-of-concept clinical trial demonstrated that a precision prebiotic intervention improved microbiota dysbiosis and alleviated gastrointestinal and motor symptoms in PD patients. Building on this, we analyzed plasma extracellular vesicles (EVs) from participants to explore EVs as a dynamic PD biomarker and to assess the systemic effects of a microbiota-directed intervention. Using mass spectrometry-based proteomics of EVs from PD and healthy control (HC) participants, we identified distinct human and bacterial proteins in plasma-derived EV. Crucially, this offers a holistic systemic readout of the microbiota-gut-brain axis by quantifying both host and microbial components. We found that EV proteomic profiles differed between PD and HC samples as well as between unmedicated/mild and medicated/moderate PD participants. Furthermore, the microbiota-directed prebiotic intervention induced an acutely modifiable PD signature, shifting host and microbial EV proteomic profiles toward the HC profile. Using a combined 16-feature host-microbe signature, we built a multiple linear regression model that accurately distinguishes PD status from HC (R2 = 0.88) and successfully stratified disease severity (R2 = 0.72). Based on these findings, we suggest that: (1) a precision prebiotic mixture can modulate PD-associated proteomic signatures and (2) plasma EV proteomics may be a platform to capture these biological responses and to explore potential diagnostic and staging biomarkers in the context of microbiome-targeted interventions.

Individual variability in gut microbiota responses limits the consistency of health benefits from prebiotic fiber interventions. Building on our concept of fiber hierarchical specificity, defined as the selective alignment and use of fibers by a narrow subset of gut microbes, we evaluated new putative high-specificity fibers for their ability to promote predictable and intense microbial shifts across individuals. Here, six candidate fibers (Acacia gum, Fucogalactan, Gellan gum, Guar gum, Locust bean gum, and Xylooligosaccharides) were tested in vitro using fecal microbiota from ten donors and compared to low-specificity (Fructooligosaccharides) and high-specificity (an insoluble glucan) reference fibers. SCFA analysis showed that Fucogalactan and Guar were strongly propiogenic, while Acacia and Locust promoted balanced SCFA production. Gellan exhibited minimal fermentability. Acacia, Fucogalactan, Guar, and Locust consistently enriched putative beneficial genera (Eisenbergiella, Hungatella, Anaerotruncus, and Parabacteroides, respectively), with strong and consistent responses across individuals, features characteristic of high-specificity fibers. In contrast, Fructooligosaccharides and Xylooligosaccharides produced more variable, and less intense responses. Our findings support Acacia, Fucogalactan, Guar, and Locust as high-specificity fibers that induce consistent, taxon-targeted shifts in the gut microbiome. These expand the repertoire of high-specificity fibers-a promising prebiotic approach for predictable microbiota modulation and related health outcomes.

IntroductionPosttraumatic stress disorder (PTSD) is a debilitating disorder characterized by intrusive memories, avoidance, negative thoughts and moods, and heightened arousal. Many patients also report gastrointestinal symptoms. Cognitive behavioral therapy (CBT) is an evidence-based treatment approach for PTSD that successfully reduces symptoms. However, many patients still meet criteria for PTSD after treatment or continue to have symptoms indicating the need for new treatment strategies for PTSD. Patients with PTSD have a disrupted intestinal microbiome (i.e., dysbiosis) which can promote neuroinflammation; thus, modulation of the microbiome could be an alternative or adjunct treatment approach for PTSD.MethodsThe current study was a 12-week, double-blind, placebo-controlled trial seeking to understand if CBT combined with a microbiota-modifying, prebiotic fiber intervention would beneficially impact clinical outcomes in veterans with PTSD (n = 70). This proof-of-concept, pilot trial was designed to assess: (1) the relationship between severity of PTSD symptoms and microbiota composition and SCFA levels (i.e., acetate, propionate, butyrate), (2) if CBT treatment with a concomitant prebiotic fiber intervention would beneficially impact clinical outcomes in veterans with PTSD, (3) evaluate the feasibility and acceptability of a prebiotic intervention as an adjunct treatment to CBT, and (4) assess the impact of treatment on the intestinal microbiota and stool SCFA (i.e., mechanism).ResultsThis study found that PTSD severity may be associated with reduced abundance of taxa capable of producing the SCFA propionate, and that a subset of individuals with PTSD may benefit from a microbiota-modifying prebiotic intervention.ConclusionThis study suggests that targeting the intestinal microbiome through prebiotic supplementation could represent a promising avenue for enhancing treatment outcomes in some individuals with PTSD.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT05424146.

Background/Objectives: Short-chain fatty acids (SCFAs) produced by gut microbiota from dietary fiber fermentation play crucial roles in health and disease. While most research focuses on individual fibers, this study investigated whether a fiber mixture could synergistically increase SCFAs, exceeding the expected average production of individual contributions and microbial signatures associated with this phenomenon. Methods: We quantified synergistic SCFA production using secondary analysis of in vitro fecal fermentation data from 33 participants across four health conditions (healthy controls, Crohn's disease, ulcerative colitis, and Parkinson's disease), by comparing observed fiber mixture output to expected additive contributions from individual components and identified microbial signatures associated with synergistic SCFA production through differential abundance and network analyses. Results: The fiber mixture consistently outperformed most individual fibers and demonstrated synergistic SCFA production, yielding 32.8 ± 20.1% more total SCFAs than expected. This synergistic effect was observed across all four health conditions studied, with many individuals showing >50% synergy and some exceeding 80%. Differential abundance analysis revealed that individuals exhibiting synergistic responses were enriched in taxa from Lachnospiraceae and Ruminococcaceae families, key butyrate-producing groups that likely facilitate cooperative interactions. Network analysis confirmed these families as central hubs in synergy-associated microbial interactions. Conclusions: These findings suggest that fiber mixtures can harness cooperative microbial interactions to synergistically enhance SCFA production regardless of health status, offering potential for developing more effective prebiotics for superior therapeutic outcomes.

We developed a home-based electronic nose (E-Nose) to passively monitor volatile organic compounds (VOCs) emitted following bowel movements and assessed its validity by correlating the output with prebiotic fiber intake. Healthy, non-overweight participants followed a three-week protocol which included the following: (1) installing the E-Nose in their bathroom; (2) activating the device following each bowel movement; (3) recording their dietary intake; (4) consuming a fiber bar (RiteCarbs) containing a blend of 10 g of prebiotic fiber daily during weeks two and three; and (5) submit stool specimens at the beginning and end of the study for 16S rRNA gene sequencing and analysis. Participants’ fecal microbiome displayed significantly increased relative abundance of putative total SCFA-producing genera (p = 0.0323) [total acetate-producing genera (p = 0.0214), total butyrate-producing genera (p = 0.0131)] and decreased Gram-negative proinflammatory genera (p = 0.0468). Prebiotic intervention significantly increased the participants’ fiber intake (p = 0.0152), E-Nose Min/Max (p = 0.0339), and area over the curve in VOC–to–fiber output (p = 0.0044). Increased fiber intake was negatively associated (R2 = 0.53, p = 0.026) with decreased relative abundance of putative Gram-negative proinflammatory genera. This proof-of-concept study demonstrates that a prototype E-Nose can noninvasively detect a direct connection between fiber intake and VOC outputs in a home-based environment.

Structurally complex corn bran arabinoxylan (CAX) was used as a model glycan to investigate gut bacteria growth and competition on different AX-based fine structures. Nine hydrolyzate segments of the CAX polymer varying in chemical structure (sugars and linkages), CAX, five less complex non-corn arabinoxylans, and xylose and glucose were ranked from structurally complex to simple. The substrate panel promoted different overall growth and rates of growth of eight Bacteroides xylan-degrading strains. For example, Bacteroides cellulosilyticus DSM 14838 (Bacteroides cellulosilyticus) grew well on an array of complex and simple structures, while Bacteroides ovatus 3-1-23 grew well only on the simple structures. In a competition experiment, B. cellulosilyticus growth was favored over B. ovatus on the complex AX-based structure. On the other hand, on the simple structure, B. ovatus strongly outcompeted B. cellulosilyticus, which was eliminated from the competitive environment by Day 11. This adaptation to fine structure and resulting competition dynamics indicate that dietary fiber chemical structures, whether complex or simple, favor certain gut bacteria. Overall, this work supports a concept that fiber degraders diversify their competitive abilities to access substrates across the spectrum of heterogeneity of fine structural features of dietary fibers.

The modern diet delivers nearly equal amounts of carbohydrates and protein into the colon representing an important protein increase compared to past higher fiber diets.

Mushroom polysaccharides consist of a unique set of polymers that arrive intact in the human large intestine becoming available for fermentation by resident gut bacteria with potential benefits to the host. Here we have obtained four glucans from two mushrooms (Pholiota nameko and Pleurotus pulmonarius) under different extraction conditions and their fermentation profile by human gut bacteria in vitro was evaluated. These glucans were isolated and characterized as (1 -> 3),(1 -> 6)-beta-D-glucans varying in branching pattern and water-solubility. An aliquot of each (1 -> 3),(1 -> 6)-beta-D-glucan was subjected to controlled smith degradation process in order to obtain a linear (1 -> 3)-beta-D-glucan from each fraction. The four beta-D-glucans demonstrated different water solubilities and molar mass ranging from 2.2 x 10(5) g.mol(-1) to 1.9 x 10(6) g.mol(-1). In vitro fermentation of the glucans by human gut microbiota showed they induced different short chain fatty acid production (52.0-97.0 mM/50 mg carbohydrates), but an overall consistent high propionate amount (28.5-30.3 % of total short chain fatty acids produced). All glucans promoted Bacteroides uniformis, whereas Anaerostipes sp. and Bacteroides ovatus promotion was strongly driven by the beta-D-glucans solubility and/or branching pattern, highlighting the importance of beta-D-glucan discrete structures to their fermentation by the human gut microbiota.

A pro-inflammatory intestinal microbiome is characteristic of Parkinson’s disease (PD). Prebiotic fibers change the microbiome and this study sought to understand the utility of prebiotic fibers for use in PD patients. The first experiments demonstrate that fermentation of PD patient stool with prebiotic fibers increased the production of beneficial metabolites (short chain fatty acids, SCFA) and changed the microbiota demonstrating the capacity of PD microbiota to respond favorably to prebiotics. Subsequently, an open-label, non-randomized study was conducted in newly diagnosed, non-medicated ( n = 10) and treated PD participants ( n = 10) wherein the impact of 10 days of prebiotic intervention was evaluated. Outcomes demonstrate that the prebiotic intervention was well tolerated (primary outcome) and safe (secondary outcome) in PD participants and was associated with beneficial biological changes in the microbiota, SCFA, inflammation, and neurofilament light chain. Exploratory analyses indicate effects on clinically relevant outcomes. This proof-of-concept study offers the scientific rationale for placebo-controlled trials using prebiotic fibers in PD patients. ClinicalTrials.gov Identifier: NCT04512599.

Dietary approaches, particularly those including fiber supplementation, can be used to promote health benefits by shaping gut microbial communities. Whereas community diversity measures, such as richness and evenness, are often used in microbial ecology to make sense of these complex and vast microbial ecosystems, it is less clear how these concepts apply when dietary fiber supplementation is given. In this perspective, we summarize and demonstrate how factors including experimental approach, number of bacteria sharing a dietary fiber, and initial relative abundances of bacteria that use a fiber can significantly affect diversity outcomes in fiber fermentation studies. We also show that a reduction in alpha diversity is possible, and perhaps expected, for most approaches that use fermentable fibers to beneficially shape the gut microbial community while still achieving health-related improvements.

Parkinson's disease (PD) is a movement disorder characterized by neuroinflammation, α-synuclein pathology, and neurodegeneration. Most cases of PD are non-hereditary, suggesting a strong role for environmental factors, and it has been speculated that disease may originate in peripheral tissues such as the gastrointestinal (GI) tract before affecting the brain. The gut microbiome is altered in PD and may impact motor and GI symptoms as indicated by animal studies, although mechanisms of gut-brain interactions remain incompletely defined. Intestinal bacteria ferment dietary fibers into short-chain fatty acids, with fecal levels of these molecules differing between PD and healthy controls and in mouse models. Among other effects, dietary microbial metabolites can modulate activation of microglia, brain-resident immune cells implicated in PD. We therefore investigated whether a fiber-rich diet influences microglial function in α-synuclein overexpressing (ASO) mice, a preclinical model with PD-like symptoms and pathology. Feeding a prebiotic high-fiber diet attenuates motor deficits and reduces α-synuclein aggregation in the substantia nigra of mice. Concomitantly, the gut microbiome of ASO mice adopts a profile correlated with health upon prebiotic treatment, which also reduces microglial activation. Single-cell RNA-seq analysis of microglia from the substantia nigra and striatum uncovers increased pro-inflammatory signaling and reduced homeostatic responses in ASO mice compared to wild-type counterparts on standard diets. However, prebiotic feeding reverses pathogenic microglial states in ASO mice and promotes expansion of protective disease-associated macrophage (DAM) subsets of microglia. Notably, depletion of microglia using a CSF1R inhibitor eliminates the beneficial effects of prebiotics by restoring motor deficits to ASO mice despite feeding a prebiotic diet. These studies uncover a novel microglia-dependent interaction between diet and motor symptoms in mice, findings that may have implications for neuroinflammation and PD.

Heavy metal exposure is a growing concern due to its adverse effects on human health, including the disruption of gut microbiota composition and function. Dietary fibers have been shown to positively impact the gut microbiota and could mitigate some of the heavy metal negative effects. This study aimed to investigate the effects of different heavy metals (As, Cd and Hg in different concentrations) on gut microbiota in the presence and absence of different dietary fibers that included fructooligosaccharides, pectin, resistant starch, and wheat bran. We observed that whereas heavy metals impaired fiber fermentation outcomes for some fiber types, the presence of fibers generally protected gut microbial communities from heavy metal-induced changes, especially for As and Cd. Notably, the protective effects varied depending on fiber types, and heavy metal type and concentration and were overall stronger for wheat bran and pectin than other fiber types. Our findings suggest that dietary fibers play a role in mitigating the adverse effects of heavy metal exposure on gut microbiota health and may have implications for the development of dietary interventions to reduce dysbiosis associated with heavy metal exposure. Moreover, fiber-type specific outcomes highlight the importance of evidence-based selection of prebiotic dietary fibers to mitigate heavy metal toxicity to the gut microbiota.

Soursop fruits are widely used in the folk medicine to treat a variety of health conditions. Once the chemical structure of dietary fibers from fruits is closely related to its biological functions in the human body, we aimed to explore structural features and biological activity of dietary fibers from soursop. Polysaccharides that constitute the soluble and insoluble fibers were extracted and further analyzed using monosaccharide composition, methylation, molecular weight determination and 13C NMR data. Soursop soluble fibers (SWa fraction) were characterized as having type II arabinogalactan and a highly methyl esterified homogalacturonan, while non-cellulosic insoluble fibers (SSKa fraction) were mainly composed by a pectic arabinan, a xylan-xyloglucan complex and a glucuronoxylan. The oral pre-treatment with SWa and SSKa promoted antinociception in mice writhing test, reducing the number of pain-like behaviors (in 84.2 % and 46.9 %, respectively, at 10 mg/kg) and peritoneal leucocyte migration (55.4 % and 59.1 %, at 10 mg/kg), effects possibly associated with the pectins present in fruit pulp extractions. SWa also significantly inhibited the plasmatic extravasation of Evans blue dye in 39.6 % at 10 mg/kg. This paper describes for the first time the structural features of soursop dietary fibers that may be of biological significance in future.