Fellipe Lopes de Oliveira

Background/Objectives: This study investigated the effects of a single dose of psilocybin-containing Psilocybe cubensis extract on gut microbiota composition, microbial metabolism, and intestinal immune-related responses. Methods: A single dose of P. cubensis extract (35 mg/L) was subjected to colonic fermentation using the SHIME^® model inoculated with fecal microbiota from individuals with severe anxiety. Psilocybin and psilocin concentrations, microbial metabolites, gut microbiota composition, intestinal barrier integrity, and cytokine responses were evaluated. Results: During colonic fermentation, the concentrations of both psilocybin and psilocin decreased significantly, suggesting their metabolism or degradation within the gut microbial environment. Treatment reduced ammonia production by 19–25% and decreased gamma-aminobutyric acid (GABA) levels. By contrast, the concentrations of the short-chain fatty acids acetic, propionic, and butyric increased by 2.26-, 2.69-, and 2.21-fold, respectively, after 20 h of fermentation. Microbial profiling revealed marked increases in the relative abundances of Bifidobacterium and Lactobacillus after 20 h and 15 days, together with a slight reduction in α-diversity. Fermentation supernatants also altered cytokine profiles and influenced intestinal barrier-related responses, although these effects reflected a complex immunomodulatory pattern rather than a uniform anti-inflammatory response. Conclusions: These findings indicate that psilocybin-containing P. cubensis extract can modulate gut microbiota composition and metabolic activity under in vitro colonic conditions. The observed changes in microbial metabolites, bacterial taxa, and host-related responses support the hypothesis that gut-microbiota-mediated mechanisms may contribute to the broader biological effects of psilocybin. However, these in vitro findings do not establish clinical benefits for intestinal or mental health, and further validation in animal models and well-controlled clinical studies is required.

Background/Objectives: Selective serotonin reuptake inhibitors (SSRIs), widely prescribed for anxiety disorders, may negatively impact the gut microbiota, contributing to dysbiosis. Considering the gut–brain axis’s importance in mental health, probiotics could represent an effective adjunctive strategy. This study evaluated the effects of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on microbiota composition, metabolic activity, and immune markers in fecal samples from patients with anxiety on SSRIs, using the SHIME^® (Simulator of the Human Intestinal Microbial Ecosystem) model. Methods: The fecal microbiotas of four patients using sertraline or escitalopram were inoculated in SHIME^® reactors simulating the ascending colon. After stabilization, a 14-day probiotic intervention was performed. Microbial composition was assessed by 16S rRNA sequencing. Short-chain fatty acids (SCFAs), ammonia, and GABA were measured, along with the prebiotic index (PI). Intestinal barrier integrity was evaluated via transepithelial electrical resistance (TEER), and cytokine levels (IL-6, IL-8, IL-10, TNF-α) were analyzed using a Caco-2/THP-1 co-culture system. The statistical design employed in this study for the analysis of prebiotic index, metabolites, intestinal barrier integrity and cytokines levels was a repeated measures ANOVA, complemented by post hoc Tukey’s tests to assess differences across treatment groups. For the 16S rRNA sequencing data, alpha diversity was assessed using multiple metrics, including the Shannon, Simpson, and Fisher indices to evaluate species diversity, and the Chao1 and ACE indices to estimate species richness. Beta diversity, which measures microbiota similarity across groups, was analyzed using weighted and unweighted UniFrac distances. To assess significant differences in beta diversity between groups, a permutational multivariate analysis of variance (PERMANOVA) was performed using the Adonis test. Results: Probiotic supplementation increased Bifidobacterium and Lactobacillus, and decreased Klebsiella and Bacteroides. Beta diversity was significantly altered, while alpha diversity remained unchanged. SCFA levels increased after 7 days. Ammonia levels dropped, and PI values rose. TEER values indicated enhanced barrier integrity. IL-8 and TNF-α decreased, while IL-6 increased. GABA levels remained unchanged. Conclusions: The probiotic combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 modulated gut microbiota composition, metabolic activity, and inflammatory responses in samples from individuals with anxiety on SSRIs, supporting its potential as an adjunctive strategy to mitigate antidepressant-associated dysbiosis. However, limitations—including the small pooled-donor sample, the absence of a healthy control group, and a lack of significant GABA modulation—should be considered when interpreting the findings. Although the SHIME^® model is considered a gold standard for microbiota studies, further clinical trials are necessary to confirm these promising results.

Type 2 diabetes is characterized by dysbiosis in the gut, which may lead to systemic inflammation. Therefore, the use of probiotics may help to achieve a balanced microbiota and improve glycemic control. The aim of this study was to verify the impact of Lactobacillus acidophilus—La5 on the gut microbiome of type 2 diabetes adults using the Human Gut Microbial Ecosystem Simulator (SHIME^®) and compare this to the microbiome of healthy subjects. Four groups (Control Group: NormoGlycemic; Treatment Group: T2D) were evaluated in SHIME^® for 6 weeks. After 7 and 14 days of colonic fermentation, the intestinal microbiota (16S rRNA gene sequencing) and metabolites (short-chain fatty acids) were analyzed. La5 altered the composition of the microbiota after 14 days of treatment for both groups, by increasing the abundance of Bacteroidetes and a decrease in Firmicutes in the NormoGlycemic. Treatment with La5 resulted in a shift in the microbial community of NormoGlycemic with increased abundance of Bacteroides and Mitsuokella and a decrease in Achromobacter and Catabacter, whereas T2D gut microbiome was enriched with Faecalibacterium and reduced in Bacteroides. Megasphaera spp. stimulated with La5 treatment in NormoGlycemic has already been reported to produce intestinal metabolites and recognized to contribute to increased anti-inflammatory and immune responses. Faecalibacterium, on the other hand, can modulate the intestinal epithelium and be a major butyrate product in the microbiota. Finally, this study showed a positive and promising result of La5 treatment in increasing intestinal homeostasis in the microbiota of T2D.

Psychobiotics are probiotics that have the characteristics of modulating central nervous system (CNS) functions or reconciled actions by the gut–brain axis (GBA) through neural, humoral and metabolic pathways to improve gastrointestinal activity as well as anxiolytic and even antidepressant abilities. The aim of this work was to evaluate the effect of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on the gut microbiota of mildly anxious adults using SHIME^®. The protocol included a one-week control period and two weeks of treatment with L. helveticus R0052 and B. longum R0175. Ammonia (NH4+), short chain fatty acids (SCFAs), gamma-aminobutyric acid (GABA), cytokines and microbiota composition were determined. Probiotic strains decreased significantly throughout the gastric phase. The highest survival rates were exhibited by L. helveticus R0052 (81.58%; 77.22%) after the gastric and intestinal phase when compared to B. longum (68.80%; 64.64%). At the genus level, a taxonomic assignment performed in the ascending colon in the SHIME^® model showed that probiotics (7 and 14 days) significantly (p < 0.005) increased the abundance of Lactobacillus and Olsenella and significantly decreased Lachnospira and Escheria-Shigella. The probiotic treatment (7 and 14 days) decreased (p < 0.001) NH₄⁺ production when compared to the control period. For SCFAs, we observed after probiotic treatment (14 days) an increase (p < 0.001) in acetic acid production and total SCFAs when compared to the control period. Probiotic treatment increased (p < 0.001) the secretion of anti-inflammatory (IL-6 and IL-10) and decreased (p < 0.001) pro-inflammatory cytokines (TNF-alpha) when compared to the control period. The gut–brain axis plays an important role in the gut microbiota, producing SCFAs and GABA, stimulating the production of anti-anxiety homeostasis. The signature of the microbiota in anxiety disorders provides a promising direction for the prevention of mental illness and opens a new perspective for using the psychobiotic as a main actor of therapeutic targets.