Table 4 Overview of other (non-MC, non-CYN) cyanobacterial metabolites’ effects on the gastrointestinal tract and/or the (gut-associated) immune system
Compound | Experimental model | Assays performed, endpoint | Exposure conditions, concentration ranges | Affected tissue(s) | Main results | References |
|---|---|---|---|---|---|---|
In vivo | ||||||
Cyanobacterial LPS | Mouse (C57BL, female) | Mortality | 0.025–1.5 mg bacterial LPS (i.p.), co-injection of 750–850 µg CyP | Whole organism | Protection against LPS-induced septic shock after 8 h (25 ng LPS; 58% survival, D-galactosamine-sensitized mice) and after 24–40 h (1.5 mg, 80% survival, non-sensitized mice) | [159] |
“Limnothrixin” (from Limnothrix AC0243) | Mouse (Balb/C, male) | Histology | 300 µL known toxin-free biomass extract (i.p.; extract 1: 180 mg dw/mL, extract 2: 195 mg dw/mL), 3–24 h | Gastrointestinal tract, small intestine (duodenum) | Loss of single cells/cell sheets in the duodenum; serum-colored mucoidal material in the gastrointestinal tract 3–10 h p.i. | [194] |
Cylindrospermopsis raciborskii biomass extract without detectable levels of CYN, MCs or saxitoxins | Mouse (Charles River, male) | Histology | 1337–1572 mg dw/kg bw (i.p.), 8–24 h | Intestines, immune system (mucosa-associated lymphoid tissue) | Enlarged Peyer’s patches | [195] |
In vitro | ||||||
Aeruginosins | n.a. (biochemical) | In vitro inhibitory assays (biochemical) | n.a. | n.a. | Serine protease inhibition, IC50 = 0.03 − > 100 µg/mL | [186] |
Anabaenolysin A | Human (primary erythrocytes) | Hemoglobin release (necrosis) | 0.38–3 µM Abl A; 1 h | Blood | EC50 (necrosis) ≈ 0.8 µM | [191] |
Cyanobacterial LPS | Human (primary monocytes) | ELISA, RT-PCR, FACS analysis | 0.1–20 µg/mL cyanobacterial LPS + 1–10 µg/mL bacterial LPS; 0–16 h | Blood (dendritic cells), innate immune system | 20-fold excess of CyP compared to LPS completely inhibited cytokine production | [159] |
Cyanobacterial LPS | Various | Pyrogenicity (LAL test, PyroGene rFC assay), leukocyte activation (chemiluminescence) | Cyanobacterial LPS extracts from M. aeruginosa-dominated bloom biomass (11 naturally occurring blooms) | Immune system | 10.2–78.3×104 EU/mg LPS (LAL test); 0.91–18.96×104 EU/mg LPS (PyroGene assay); leukocyte activation observed | [157] |
Cylindrospermopsin- containing biomass extracts | n.a. | Skin sensitization | Human health risk assessment, literature review | Skin, immune system | Skin sensitization occurred in a cylindrospermopsin-independent manner, implying other irritating agents in the bloom biomass | [176] |
Cyanobacterial biomass (Spirulina platensis) hot water extract | Human (blood, male volunteers) | Cytokine production and responsiveness, natural killer cell cytolytic activity | 50 mL extract/volunteer/day, 1–8 weeks | Whole organism, blood | Internalization of uncharacterized Spirulina components via GIT; prestimulation of monocytes. Targets: monocytes (additive effect on TLR-mediated cytokine production) and natural killer (NK) cells (upregulation of cytolysis and IFN; critically affected by IL-18 levels) | [196] |
Cyanopeptolin CP1020 | Danio rerio (whole embryo) | Transcriptomics | 0.1–1 mg/L CP1020, 96 h | Whole embryo | Pathways altered ≥ 2-fold: DNA damage recognition and repair, circadian rhythm, response to light | [189] |
Puwainaphycin F, minutissamides A and C | Human (CaCo-2 cells) | ELISA | Non-cytotoxic concentrations of PUWF, MIN A, MIN C; 24 h | Intestine (colon) | Increased secretion of IL-8, altered expression of tight junction protein | [193] |
Puwainaphycins F/G | Mouse (YAC-1 cells), human (HeLa cells) | MTT assay, intracellular Ca2+ concentration | 1–10 µM PUW, 10 min–10 h | Lymphoma, cervical cancer | EC50 (necrosis) 2.2 µM | [192] |