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An alkaline-extracted low-molecular-weight heteroglucan from Ganoderma lucidum enhances immunity by modulating the gut microbiota

ABSTRACT:

Ganoderma lucidum polysaccharides exhibit various biological activities, but conventional extraction is biased toward high-molecular-weight polymers. This study aimed to explore the structure and bioactivity of low-molecular-weight polysaccharides from Ganoderma lucidum, referred to as AGLP1. A low-molecular-weight heteroglucan from Ganoderma lucidum was purified by alkaline extraction, membrane filtration and column chromatography. Structural characterization indicated that AGLP1, with an approximate molecular weight of 9.0 kDa, is a heteroglucan mainly composed of a 1,3-linked glucopyranosyl backbone with 1,6-linked glucopyranosyl side chains. In vivo investigations showed that AGLP1 enhanced the spleen index, macrophage phagocytic activity and proliferation of T and B lymphocytes. These immunomodulatory effects were gut microbiota-dependent, as they were reduced in microbiota-depleted mice after antibiotic treatment. Mechanistically, AGLP1 reshaped the gut microbiota and metabolite profile by enriching potentially beneficial bacteria such as Ruminococcaceae and Eubacterium brachy group, as well as associated metabolites including decanoic acid, stearic acid and pimelic acid. In vitro fermentation using a human fecal model showed that AGLP1 also increased the abundances of Ruminococcaceae and Eubacterium brachy group. These findings indicate that AGLP1 has immunomodulatory and microbiota-reshaping effects and may have potential as a functional food ingredient.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS14649 | MetaboLights | 2026-06-18

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS14649_LC-MS_negative_reverse-phase.txt	Txt
	a_MTBLS14649_LC-MS_positive_reverse-phase.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS14649_LC-MS_negative_reverse-phase_v2_maf.tsv	Tabular
	m_MTBLS14649_LC-MS_positive_reverse-phase_v2_maf.tsv	Tabular

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Project description:Background: Dendrobium officinale, an endangered Chinese herb, has extensive therapeutic effects and contains bioactive ingredients including a large number of polysaccharides and alkaloids, and minimal flavonoids. Firstly, this study attempts to obtain the protocorm-like bodies of this plant through tissue culture to produce the main secondary metabolites whose distribution in each organelle and protocorm like bodies is analyzed. Then, analysis of the correlation between comparative transcriptome sequence and the metabolite content in different organs enables the discovery of putative genes encoding enzymes involved in the biosynthesis of polysaccharides and alkaloids, and flavonoids. Results: The optimum condition for protocorm-like bodies (PLBs) induction and propagation of D. officinale is established. For protocorm induction, we use the seed as the explant, and the optimum medium formula for PLBs propagation is 1/2 MS + α-NAA 0.5 mg·L-1 +6-BA 1.0 mg·L-1 + 2, 4-D 1.5-2.0 mg·L-1 + potato juice 100 g·L-1. The distribution of polysaccharides, alkaloids and flavonoids in D. officinale organs was clarified. Stems, PLBs and leaves have the highest content of polysaccharides, alkaloids and flavonoids, respectively. PLBs replace organs to produce alkaloids in D. officinale, and naringenin was only produced in stem. Hot water extraction (HWE) method was found outperforming the ultrasound-assisted extraction (UAE) method for polysaccharides from D. officinale. A comparative transcriptome analysis of the protocorm-like bodies and leaves of D. officinale showed genes encoding enzymes involved in polysaccharides, alkaloids and flavonoids biosynthetic pathway were differentially expressed. Putative genes encoding enzymes involved in polysaccharides, alkaloids and flavonoids synthetic pathway were identified. Notably, genes encoding enzymes of strictosidine beta-glucosidase, geissoschizine synthase and vinorine synthase in alkaloids biosynthesis of D. officinale are first reported. Conclusions: Our works, especially the identification of candidate genes encoding enzymes involved in metabolites biosynthesis will help to explore and protect the endangered genetic resources and will also facilitate further analysis of the molecular mechanism of secondary metabolites’ biosynthesis in D. officinale.

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An alkaline-extracted low-molecular-weight heteroglucan from Ganoderma lucidum enhances immunity by modulating the gut microbiota

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