Kreuzer Kathrin, Reiter Alexandra, Birkl-Töglhofer Anna Maria, Dalkner Nina, Mörkl Sabrina, Mairinger Marco, Fleischmann Eva, Fellendorf Frederike, Platzer Martina, Lenger Melanie, Färber Tanja, Seidl Matthias, Birner Armin, Queissner Robert, Mendel Lilli-Marie Stefanie, Maget Alexander, Kohlhammer-Dohr Alexandra, Häussl Alfred, Wagner-Skacel Jolana, Schöggl Helmut, Amberger-Otti Daniela, Painold Annemarie, Lahousen-Luxenberger Theresa, Leitner-Afschar Brigitta, Haybaeck Johannes, Habisch Hansjörg, Madl Tobias, Reininghaus Eva, Bengesser Susanne
Psychosomatics and Psychotherapy Clinical Department of Psychiatry and Psychotherapeutic Medicine, University Hospital for Psychiatry, Medical University of Graz, 8036 Graz, Austria.
Neuropathology and Molecular Pathology, Institute for Pathology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Metabolites. 2022 Aug 21;12(8):770. doi: 10.3390/metabo12080770.
The gut-brain axis plays a role in major depressive disorder (MDD). Gut-bacterial metabolites are suspected to reduce low-grade inflammation and influence brain function. Nevertheless, randomized, placebo-controlled probiotic intervention studies investigating metabolomic changes in patients with MDD are scarce. The PROVIT study (registered at clinicaltrials.com NCT03300440) aims to close this scientific gap. PROVIT was conducted as a randomized, single-center, double-blind, placebo-controlled multispecies probiotic intervention study in individuals with MDD ( = 57). In addition to clinical assessments, metabolomics analyses (1H Nuclear Magnetic Resonance Spectroscopy) of stool and serum, and microbiome analyses (16S rRNA sequencing) were performed. After 4 weeks of probiotic add-on therapy, no significant changes in serum samples were observed, whereas the probiotic groups' ( = 28) stool metabolome shifted towards significantly higher concentrations of butyrate, alanine, valine, isoleucine, sarcosine, methylamine, and lysine. Gallic acid was significantly decreased in the probiotic group. In contrast, and as expected, no significant changes resulted in the stool metabolome of the placebo group. Strong correlations between bacterial species and significantly altered stool metabolites were obtained. In summary, the treatment with multispecies probiotics affects the stool metabolomic profile in patients with MDD, which sets the foundation for further elucidation of the mechanistic impact of probiotics on depression.
肠-脑轴在重度抑郁症（MDD）中发挥作用。肠道细菌代谢产物被怀疑可减轻低度炎症并影响脑功能。然而，针对MDD患者代谢组学变化的随机、安慰剂对照益生菌干预研究却很匮乏。PROVIT研究（在clinicaltrials.com上注册，编号NCT03300440）旨在填补这一科学空白。PROVIT研究是一项针对MDD患者（n = 57）的随机、单中心、双盲、安慰剂对照的多菌种益生菌干预研究。除了临床评估外，还进行了粪便和血清的代谢组学分析（1H核磁共振波谱法）以及微生物组分析（16S rRNA测序）。在进行4周的益生菌附加治疗后，血清样本未观察到显著变化，而益生菌组（n = 28）的粪便代谢组向丁酸盐、丙氨酸、缬氨酸、异亮氨酸、肌氨酸、甲胺和赖氨酸浓度显著升高的方向转变。益生菌组中没食子酸显著降低。相比之下，正如预期的那样，安慰剂组的粪便代谢组没有显著变化。获得了细菌种类与粪便代谢产物显著改变之间的强相关性。总之，多菌种益生菌治疗会影响MDD患者的粪便代谢组学特征，这为进一步阐明益生菌对抑郁症的作用机制奠定了基础。
