Targeted remodeling of the human gut microbiome using Juemingzi (Senna seed extracts)

Authors: Narrowe, Adrienne; Scarino Lemons, Johanna; Mahalak, Karley; Firrman, Jenni; VAN DEN ABBEELE, PIETER - Cryptobiotix; BAUDOT, AURELIEN - Cryptobiotix; DEYAERT, STEF - Cryptobiotix; LI, YANFANG - University Of Maryland; YU, LIANGLI - University Of Maryland; Liu, Linshu

Submitted to: Frontiers in Cellular and Infection Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/19/2024
Publication Date: 4/4/2024
Citation: Narrowe, A.B., Scarino Lemons, J.M., Mahalak, K.K., Firrman, J., Van Den Abbeele, P., Baudot, A., Deyaert, S., Li, Y., Yu, L., Liu, L.S. 2024. Targeted remodeling of the human gut microbiome using Juemingzi (Senna seed extracts). Frontiers in Cellular and Infection Microbiology. 14. https://doi.org/10.3389/fcimb.2024.1296619.
DOI: https://doi.org/10.3389/fcimb.2024.1296619

Interpretive Summary: Senna plants are found worldwide, and components of these plants are used for a variety of purposes, including for Senna’s best-known use as a laxative. When consumed, the Senna plant components encounter the gut microbiome, which is the collection of microorganisms inhabiting the human gut. The microbiome plays important roles in human health and nutrition, but, despite its well-known use that acts directly on the gastrointestinal tract, there is limited knowledge of how Senna affects the gut microbiome. To understand the effects of these extracts on intact gut microbiomes, we tested extracts of Senna seeds using fecal incubations. We found that these extracts had a dramatic inhibitory effect on the human gut microbiome, broadly reducing the overall bacterial numbers and at the same time specifically targeting certain bacterial groups. This unexpected specificity suggests additional uses for components derived from members of this broadly available plant family.

Technical Abstract: The genus Senna contains globally distributed plant species of which the leaves, roots, and seeds have multiple traditional medicinal and nutritional uses. Notable chemical compounds derived from Senna spp. include sennosides and emodin which have been tested for antimicrobial effects in addition to their known laxative functions. However, studies of the effects of the combined chemical components on intact human gut microbiome communities are lacking. Here we addressed this knowledge gap using SIFR® (Systemic Intestinal Fermentation Research) technology. After a 48-hour human fecal incubation, we measured total bacterial cell density and fermentation products including pH, gas production and concentrations of short chain fatty acids (SCFAs). The initial and post-incubation microbial community structure and functional potential were characterized using shotgun metagenomic sequencing. Senna seed extracts displayed strong, taxon-specific anti-microbial effects as indicated by significant reductions in cell density (40%) and intra-sample community diversity. Members of the Bacteroidetes were nearly eliminated over the 48-hour incubation. While generally part of a healthy gut microbiome, specific Bacteroides sp. can be pathogenic. The active persistence of the members of the Enterobacteriaceae and selected Actinobacteria despite the reduction in overall cell numbers was demonstrated by increased fermentative outputs including high concentrations of gas and acetate with correspondingly reduced pH. The resulting dominance by members of the Enterobacteriaceae may have mixed effects in practice, indicating the need for further evaluation of dosages and prebiotic or symbiotic supplements. Overall, the very specific effects of these extracts may offer the potential for targeted antimicrobial uses or as a tool in the targeted remodeling of the gut microbiome.