PapRIV, a BV-2 microglial cell activating quorum sensing peptide

Janssens, Yorick; Debunne, Nathan; Spiegeleer, Anton De; Wynendaele, Evelien; Planas, Marta; Feliu, Lidia; Quarta, Alessandra; Claes, Christel; Dam, Debby Van; Deyn, Peter Paul De; Ponsaerts, Peter; Blurton-Jones, Matthew; Spiegeleer, Bart De

doi:10.1038/s41598-021-90030-y

Cited by 24 publications

(18 citation statements)

References 79 publications

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“…Our study showed that SG could ameliorate CUMS-induced depression, and the underlying mechanism may be associated with improvements in gut microbiota composition and changes in intestinal inflammation and glutamate metabolism. It is known that microorganisms and the brain communicate with each other through the immune system, tryptophan metabolism, vagus nerve, and enteric nervous system ( Janssens et al, 2021 ). This communication involves a variety of microbial metabolites, such as pro-inflammatory factors, short-chain fatty acids, and neurotransmitters.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant Shugan Jieyu Capsule Alters Gut Microbiota and Intestinal Microbiome Function in Rats With Chronic Unpredictable Mild Stress -Induced Depression

Tan

Zhu

et al. 2022

Front. Pharmacol.

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Shugan Jieyu Capsule (SG) has been widely used in China to treat mild to moderate depression. Hypericum perforatum L. (St John’s Wort, SJW) is the main ingredient of SG and has been used as herbal medicine to treat depression in western countries. However, it is known that SJW has low bioavailability and does not easily get through the blood-brain barrier. Therefore, how SG plays an antidepressant effect in the central nervous system (CNS) remains an urgent problem to be solved. Mounting research has described the relationship between antidepressants and intestinal microbiota to illuminate antidepressive mechanisms in the CNS. We aimed to investigate the effects of therapy with SG on the function of gut microbiota and intestinal microbiota in rats with chronic unpredictable mild stress (CUMS)-induced depression. The psychophysiological state and the hypothalamic-pituitary-adrenal axis function of rats are evaluated through behavioral experiments, corticosterone levels, serotonin levels, and adrenal index measurements. 16S rDNA amplicon sequencing is used to test the changes in gut microbiota and make functional predictions of genes. With treatment of SG, the depression-like behaviors of CUMS-induced rats were reversed; the corticosterone levels and the adrenal index decreased significantly; the level of serotonin increased significantly; and the alpha and beta diversity analysis of microbiota showed an increase in the richness and uniformity of the flora were increased. SG regulated the relative abundance of Actinobacteria, Erysipelotrichaceae, Bifidobacteriaceae, Atopobiaceae, Dubosiella, and Bifidobacterium; Linear discriminant analysis effect size analysis demonstrated that Lactobacillaceae (family level), Lactobacillus (genus level), Lactobacillales (order level), Bacilli (class level), and Lactobacillus-reuteri (species level) were biomarkers in the SG group samples, and also likely to modulate metabolic pathways, such as those involved in carbohydrate metabolism, amino acid metabolism, and signal transduction. These data clearly illustrated the effect of SG on gut microbiome, thus laying the foundation for uncovering more insights on the therapeutic function of the traditional Chinese antidepressants. The potential of SG on mechanisms of antidepression to alter gut microbiota and intestinal microbiome function exposed to CUMS can be explored.

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Section: Discussionmentioning

confidence: 99%

Antidepressant Shugan Jieyu Capsule Alters Gut Microbiota and Intestinal Microbiome Function in Rats With Chronic Unpredictable Mild Stress -Induced Depression

Tan

Zhu

et al. 2022

Front. Pharmacol.

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“…QS peptides PapRIV produced by Bacillus cereus species have been found to be able to cross the gastrointestinal tract and the BBB and reach the brain to activate the production of proinflammatory cytokines by microglia leading to neurotoxic effects. 179 In vitro infection of macrophages by Group A Streptococcus was also found to inhibit their activation and production of proinflammatory cytokines through QS signalling. 183 The QS molecule N-3O-dodecanoylhomoserine lactone (3O-C12) produced by Pseudomonas aeruginosa (P. aeruginosa) is able to modulate immune responses through multiple mechanisms.…”

Section: The Interplay Between Microbial Qs and Their Mammalian Hostmentioning

confidence: 99%

“…Bacterial QS has also been found to modulate the functions of human neural and immune cells via a range of QS molecular targets that are expressed on the host cells 178,179 (Figure 3a). In a mouse study, three chemically diverse QS oligopeptides were found to be able to cross the BBB and influx into the mouse brain 180 .…”

Section: The Contribution Of Microbial Quorum Sensing In Cellular Def...mentioning

confidence: 99%

“…While QS signals from commensal microbiota support gut homeostasis and immunity, those from pathogens can promote infection by manipulating the host immune system 178 (Figure 3b). QS peptides PapRIV produced by Bacillus cereus species have been found to be able to cross the gastrointestinal tract and the BBB and reach the brain to activate the production of proinflammatory cytokines by microglia leading to neurotoxic effects 179 . In vitro infection of macrophages by Group A Streptococcus was also found to inhibit their activation and production of proinflammatory cytokines through QS signalling 183 .…”

Section: The Contribution Of Microbial Quorum Sensing In Cellular Def...mentioning

confidence: 99%

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Importance of crosstalk between the microbiota and the neuroimmune system for tissue homeostasis

Mehta

et al. 2022

Clin & Trans Imm

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The principal function of inflammation is cellular defence against ‘danger signals’ such as tissue injury and pathogen infection to maintain the homeostasis of the organism. The initiation and progression of inflammation are not autonomous as there is substantial evidence that inflammation is known to be strongly influenced by ‘neuroimmune crosstalk’, involving the production and expression of soluble signalling molecules that interact with cell surface receptors. In addition, microbiota have been found to be involved in the development and function of the nervous and immune systems and play an important role in health and disease. Herein, we provide an outline of the mechanisms of neuroimmune communication in the regulation of inflammation and immune response and then provide evidence for the involvement of microbiota in the development and functions of the host nervous and immune systems. It appears that the nervous and immune systems in multicellular organisms have co‐evolved with the microbiota, such that all components are in communication to maximise the ability of the organism to adapt to a wide range of environmental stresses to maintain or restore tissue homeostasis.

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“…These permeability coefficients are higher than for other bioactive peptides, of which some have been detected in murine plasma in the past. 6 , 8 , 9 , 10 To explore the potential of iAM373 to cross the gut barrier and reach systemic circulation in vivo, germ‐free mice were inoculated with genetically modified E. coli that continuously produce iAM373. When the mice were treated with these bacteria through oral gavage, iAM373 was detected in the blood circulation; mice untreated or treated with unmodified E. coli (placebo) did not display iAM373 in their blood (Figure 2B,C ).…”

mentioning

confidence: 99%