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Page 8 of 14 Tian et al. Microbiome Res Rep 2024;3:49 https://dx.doi.org/10.20517/mrr.2024.33

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Figure 3. Pediococcus acidilactici CCFM6432’s effect on the gut microbiota of depressed patients. (A) α-diversity - Chao1 index; P < 0.01
in paired t-test; (B-D) PCA of gut microbiota composition; PERMANOVA was used to assess β-diversity differences between groups; (E)
LEfSe analysis of differential microbial species between groups (Wilcoxon rank-sum test, α < 0.05 and log LDA > 2.0 were used as the
threshold); (F and G) Predicted genomic functions of gut microbiota and enrichment analysis of immune and neural function-related
signaling pathways. The metagenomic composition was predicted from 16S rRNA sequences and annotated based on the reference
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database (KEGG). P < 0.05 in the unpaired t-tests. PCA: Principal component analysis; PERMANOVA: permutational multivariate
analysis of variance; LEfSe: linear discriminant analysis effect size; LDA: linear discriminant analysis; KEGG: Kyoto Encyclopedia of
Genes and Genomes.

and metabolic diseases such as alcoholic fatty liver and diabetes [27,28] . Additionally, the abundance of
[29]
Megamonas in the feces of autistic children was significantly higher than in healthy children . In contrast,
differences in microbial species after placebo treatment were mainly contributed by Pediococcus,
Ruminococcaceae UCG_003, Lachnospiraceae UCG_010, and the Ruminococcus gauvreauii group. Previous
research has indicated that the abundance of Lachnospiraceae, Ruminococcaceae, and Ruminococcus in the
gut of patients with severe depression is lower than in healthy controls [30,31] , suggesting that taking
CCFM6432 helps promote the proliferation of microbial species positively associated with host emotional
responses.

Considering the well-known ability of Pediococcus to produce lactic acid and inhibit the growth of
pathogenic bacteria, we performed annotation analysis of the microbial genome functions (focusing on
immune and nervous system-related signaling pathways) to explore the potential impact of the gut
microbiota on host physiology. We found that the annotated genes in the pathways of Antigen processing
and presentation, Th17 cell differentiation, and NOD-like receptor signaling pathway were lower in the
CCFM6432-modified microbiota [Figure 3F]. Particularly, the NOD-like receptor signaling pathway, a
critical pathway involved in pathogen recognition and innate immune response, showed a statistically
significant difference between the CCFM6432 and placebo groups (P = 0.020). However, there were no