Biogeography of the large intestinal mucosal and luminal microbiome in cynomolgus macaques with depressive-like behavior

Abstract

Most previous studies in the pathophysiology of major depressive disorder (MDD) focused on fecal samples, which limit the identification of the gut mucosal and luminal microbiome in depression. Here, we address this knowledge gap. Male cynomolgus macaques (Macaca fascicularis) were randomly assigned to a chronic unpredictable mild stress (CUMS) group, or to an unstressed control group. Behavioral tests were completed in both groups. At endpoint, microbe composition of paired mucosal and luminal samples from cecum, ascending, transverse, and descending colons were determined by 16S ribosomal RNA gene sequencing. The levels of 34 metabolites involved in carbohydrate or energy metabolism in luminal samples were measured by targeted metabolomics profiling. CUMS macaques demonstrated significantly more depressive-like behaviors than controls. We found differences in mucosal and luminal microbial composition between the two groups, which were characterized by Firmicutes and Bacteriodetes at the phylum level, as well as Prevotellaceae and Lachnospiraceae at the family level. The majority of discriminative microbes correlated with the depressive-like behavioral phenotype. In addition, we found 27 significantly different microbiome community functions between the two groups in mucosa, and one in lumen, which were mainly involved in carbohydrate and energy metabolism. A total of nine metabolites involved in these pathways were depleted in CUMS animals. Together, CUMS macaques with depressive-like behaviors associated with distinct alterations of covarying microbiota, carbohydrate and energy metabolism in mucosa and lumen. Further studies should focus on the mucosal and luminal microbiome to provide a deeper spatiotemporal perspective of microbial alterations in the pathogenesis of MDD.

Heterogeneity and Co-occurrence in the Luminal and Mucosal Gut Microbiomes and Metabolomes of Oriental Rat snake (Ptyas mucosus)

“…Studies of human microbiomes have shown that the mucosal microbiome is more stable than the fecal microbiome [33]; in swine, Firmicutes abundance was more stable in the mucosal microbiome than in the luminal microbiome [17]. Nevertheless, other studies involving chicken [15], cattle [34], and macaques [14,35] have not revealed differences in terms of within-group stability between luminal and mucosal/epithelial microbiomes. These results suggest that the mucosal niche supports a more stable microbial community, particularly in snakes, where the luminal microbiome is likely to be strongly affected by the state of absorption and recent diet; their dietary pattern involves intermittent fasting, which can cause dynamic changes in luminal contents [31,36].…”

“…Analysis of the human microbiome revealed greater abundances of Firmicutes and Bacteroidota in stool, whereas the abundance of Proteobacteria was greater in mucosa [13]. In macaques, Bacteroidetes was dominant in both luminal and mucosal microbiomes, whereas Firmicutes was more abundant in the luminal microbiome and Proteobacteria was more abundant in the mucosal microbiome [14,35]. In cattle, Firmicutes and Proteobacteria were more abundant in epimural biopsy samples, whereas Bacteroidetes and Proteobacteria were more abundant in luminal samples [34,39].…”

The Aurantii Fructus Immaturus flavonoid extract alleviates inflammation and modulate gut microbiota in DSS-induced colitis mice

“…We also noticed that the abundance of Prevotellaceae and Lachnospiraceae was significantly increased in the AFIM and AFIH groups, respectively. In fact, Prevotellaceae, a butyric acid-producing probiotic, is thought to be associated with anti-inflammatory and antioxidant activities ( 1 , 28 , 29 ). In addition, based on Spearman correlation analysis of intestinal inflammatory factors and intestinal microbiota, we found positive and negative correlations between the abundance of some bacteria and inflammation.…”

Mapping trends and hotspot regarding gastrointestinal microbiome and neuroscience: A bibliometric analysis of global research (2002–2022)

“…In addition, numerous experts in microbiology and neuroscience from Ireland, China, the United States, and other countries have studied the characteristics of the gastrointestinal microbiota in health and neuroscience disease states, the connection between pathological function and neuroscience disease, and other topics. These professionals, who serve as a foundation for the creation and publication of papers in this area, include Cryan JF, Dinan TG, Clarke G, Stanton C, O’Mahony SM, Bastiaanssen TFS, Yang C, Xie P, Bailey MT, Green SJ, Keshavarzian A, and Forsyth CB ( Clarke et al, 2013 ; Dinan et al, 2014 ; Mayer et al, 2014 ; Stilling et al, 2015 ; Tarr et al, 2015 ; Dodiya et al, 2020 ; Joers et al, 2020 ; Li et al, 2020 ; van de Wouw et al, 2020 ; Frausto et al, 2021 ; Zheng et al, 2021 ; Connell et al, 2022 ; Teng et al, 2022 ). It is worth noting that the citations of articles published in the United States rank first, followed by Ireland and China.…”