Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 Jan-Dec;16(1):2347715.
doi: 10.1080/19490976.2024.2347715. Epub 2024 May 8.

Metabolome-associated psychological comorbidities improvement in irritable bowel syndrome patients receiving a probiotic

Francois-Pierre Martin  1 , Ornella Cominetti  2 , Bernard Berger  1 , Séverine Combremont  1 , Julien Marquis  1 , Guoxiang Xie  3   4 , Wei Jia  3   5 , Maria Inés Pinto-Sanchez  6 , Premysl Bercik  6 , Gabriela Bergonzelli  1
Affiliations
Randomized Controlled Trial

Metabolome-associated psychological comorbidities improvement in irritable bowel syndrome patients receiving a probiotic

Francois-Pierre Martin et al. Gut Microbes. 2024 Jan-Dec.

Abstract

Our recent randomized, placebo-controlled study in Irritable Bowel Syndrome (IBS) patients with diarrhea or alternating bowel habits showed that the probiotic Bifidobacterium longum (BL) NCC3001 improves depression scores and decreases brain emotional reactivity. However, the involved metabolic pathways remain unclear. This analysis aimed to investigate the biochemical pathways underlying the beneficial effects of BL NCC3001 using metabolomic profiling. Patients received probiotic (1x 1010CFU, n=16) or placebo (n=19) daily for 6 weeks. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Brain activity in response to negative emotional stimuli was assessed by functional Magnetic Resonance Imaging. Probiotic fecal abundance was quantified by qPCR. Quantitative measurement of specific panels of plasma host-microbial metabolites was performed by mass spectrometry-based metabolomics. Probiotic abundance in feces was associated with improvements in anxiety and depression scores, and a decrease in amygdala activation. The probiotic treatment increased the levels of butyric acid, tryptophan, N-acetyl tryptophan, glycine-conjugated bile acids, and free fatty acids. Butyric acid concentration correlated with lower anxiety and depression scores, and decreased amygdala activation. Furthermore, butyric acid concentration correlated with the probiotic abundance in feces. In patients with non-constipation IBS, improvements in psychological comorbidities and brain emotional reactivity were associated with an increased abundance of BL NCC3001 in feces and specific plasma metabolites, mainly butyric acid. These findings suggest the importance of a probiotic to thrive in the gut and highlight butyric acid as a potential biochemical marker linking microbial metabolism with beneficial effects on the gut-brain axis.

Keywords: Irritable bowel syndrome (IBS); depression; emotional reactivity; metabolomics, butyrate; probiotic.

PubMed Disclaimer

Conflict of interest statement

GB, BB, SC, JM, FPM, and OC are employees of Société des Produits Nestlé S.A., Switzerland. WJ, GX, and PB received research support from Société des Produits Nestlé, SA. PB holds the Richard Hunt-AstraZeneca Chair in Gastroenterology.

Figures

Figure 1.
Figure 1.
Fecal BL NCC3001 relative abundance and associations with clinical outcomes.
Figure 2.
Figure 2.
OPLS samples and variable plots.
Figure 3.
Figure 3.
Overview of changes in plasma fatty acids and bile acids.
Figure 4.
Figure 4.
Overview of changes in plasma tryptophan, N-Acetyl tryptophan, and associations with clinical endpoints.
Figure 5.
Figure 5.
Overview of changes in plasma butyric acid and associations with clinical endpoints and fecal BL NCC3001 counts.
See this image and copyright information in PMC

References

    1. Collins SM, Surette M, Bercik P.. The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol. 2012;10(11):735–12. doi:10.1038/nrmicro2876. - DOI - PubMed
    1. Lin L, Zhang J. Role of intestinal microbiota and metabolites on gut homeostasis and human diseases. BMC Immunol. 2017;18(1):2. doi:10.1186/s12865-016-0187-3. - DOI - PMC - PubMed
    1. Cryan JF, O’Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV. et al. The microbiota-gut-brain axis. Physiol Rev. 2019;99(4):1877–2013. doi:10.1152/physrev.00018.2018. - DOI - PubMed
    1. Lyte M, Brown DR, Yamashita A. Evidence for PMAT- and OCT-like biogenic amine transporters in a probiotic strain of lactobacillus: implications for interkingdom communication within the microbiota-gut-brain axis. PloS One. 2018;13(1):e0191037. doi:10.1371/journal.pone.0191037. - DOI - PMC - PubMed
    1. Strandwitz P, Kim KH, Terekhova D, Liu JK, Sharma A, Levering J, McDonald D, Dietrich D, Ramadhar TR, Lekbua A. et al. GABA-modulating bacteria of the human gut microbiota. Nat Microbiol. 2019;4(3):396–403. doi:10.1038/s41564-018-0307-3. - DOI - PMC - PubMed

Publication types