Alterations to microbial secretome by estrogen may contribute to sex bias in irritable bowel syndrome

Pretorius, Lesha; Staden, Anton D. van; Merwe, Johannes J Van der; N, Henning; Smith, Carine

doi:10.1007/s10787-021-00906-8

Cited by 5 publications

(5 citation statements)

References 79 publications

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“…Despite the relatively similar effects of TYR and AGM-in line with our previous work [37]-in altering both PGE and IL-8 levels and increasing total TJP concentrations, an important differentiating factor in these effects is related, in particular, to the distribution of occludin. In the case of TYR, as mentioned previously, extensive occludin internalisation (i.e., loss of colocalisation with ZO-1) was observed, while exposure to AGM promoted ZO-1 and occludin colocalisation in areas of intact monolayer, but with apparent loss of TJP expression in other areas.…”

Section: Discussionsupporting

confidence: 83%

“…According to Wan et al (2019), two crucial factors determine gut health, namely the gut microbiota and the intestinal epithelial barrier. Indeed, in line with our current hypothesis of trace-aminergic involvement in exaggeration of gastrointestinal symptomology [36], we have recently demonstrated the deleterious effects of high trace-amine (TA) load on intestinal epithelial tight-junction proteins (TJPs) and inflammatory status [37]. In this regard, we propose that the known poor absorption and low systemic bioavailability of rooibos and some of its polyphenolic constituents [38][39][40] may not be a significant limitation if beneficial modulation of rooibos occurs directly at an intestinal epithelial level.…”

Section: Introductionsupporting

confidence: 67%

“…Current data implicate TYR especially in PGE2 stimulation. This has specific relevance to gastrointestinal disorders, as elevated levels of faecal TYR were identified as a differential biomarker in patients with inflammatory bowel disease in a cross-sectional study [52] and TYR has demonstrated cellular cytotoxicity at high doses [37,66]. Furthermore, we and others have demonstrated that TYR is an abundant microbial metabolite [32,67,68].…”

Section: Discussionmentioning

confidence: 73%

“…In order to investigate the ability of GRE to mediate gut health, HT-29 cells were exposed to TA doses previously demonstrated to detrimentally affect TJP profile [37]. Briefly, HT-29 cells were seeded at 1.5 × 10 5 cells/well (24-well plate) onto sterilized 12 mm round glass coverslips, which were previously coated with ECL cell-attachment matrix (Merck, Rahway, NJ, USA, 08-110) and refreshed every other day.…”

Section: Tight-junction Protein Immunofluorescent Stainingmentioning

confidence: 99%

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Aspalathus linearis (Rooibos) and Agmatine May Act Synergistically to Beneficially Modulate Intestinal Tight Junction Integrity and Inflammatory Profile

Pretorius

Smith

2022

Pharmaceuticals

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In order to promote gastrointestinal health, significant increases in the prevalence of gastrointestinal disorders should be paralleled by similar surges in therapeutics research. Nutraceutical interventions may play a significant role in patient management. The current study aimed to determine the potential of Aspalathus linearis (rooibos) to prevent gastrointestinal dysregulation resulting from high-dose trace-amine (TA) exposure. Considering the substantial female bias in functional gastrointestinal disorders, and the suggested phytoestrogenicity of rooibos, the study design allowed for a comparison between the effects of an ethanol extract of green rooibos and 17β-estradiol (E2). High levels of ρ-tyramine (TYR) and agmatine (AGM), but not β-phenethylamine (PEA) or tryptamine (TRP), resulted in prostaglandin E2 (PGE2) hypersecretion, increased tight-junction protein (TJP; occludin and ZO-1) secretion and (dissimilarly) disrupted the TJP cellular distribution profile. Modulating benefits of rooibos and E2 were TA-specific. Rooibos pre-treatment generally reduced IL-8 secretion across all TA conditions and prevented PGE2 hypersecretion after exposure to both TYR and AGM, but was only able to normalise TJP levels and the distribution profile in AGM-exposed cells. In contrast, E2 pre-treatment prevented only TYR-associated PGE2 hypersecretion and TJP dysregulation. Together, the data suggest that the antioxidant and anti-inflammatory effects of rooibos, rather than phytoestrogenicity, affect benefits illustrated for rooibos.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 73%

Section: Tight-junction Protein Immunofluorescent Stainingmentioning

confidence: 99%

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Aspalathus linearis (Rooibos) and Agmatine May Act Synergistically to Beneficially Modulate Intestinal Tight Junction Integrity and Inflammatory Profile

Pretorius

Smith

2022

Pharmaceuticals

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“…Potential for an approach to ameliorate effects of estrogen on the microbial secretome (i.e. correcting functional, rather than compositional dysbiosis) has been demonstrated in irritable bowel syndrome, where modulation of the effect of estrogen on microbial secretome resulted in therapeutic benefit in terms of inflammatory outcome and endothelial integrity (Pretorius and Smith 2020 , 2023 ; Pretorius et al 2022 ). Despite the central role of inflammation and endothelial damage in LN, this potential therapeutic route remains largely unexplored.…”

Section: Bmp-7: a Link To Sexual Disparity In Lnmentioning

confidence: 99%

Potential of bone morphogenetic protein-7 in treatment of lupus nephritis: addressing the hurdles to implementation

Smith,

du Toit,

Ollewagen

2023

Inflammopharmacol

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Up to 50% of systemic lupus erythematosus (SLE) patients world-wide develop lupus nephritis (LN). In low to middle income countries and in particular in sub-Saharan Africa, where SLE is prevalent with a more aggressive course, LN and end stage renal disease is a major cause of mortality. While developed countries have the funding to invest in SLE and LN research, patients of African descent are often underrepresented in clinical trials. Thus, the complex influence of ethnicity and genetic background on outcome of LN and SLE as a whole, is not fully understood. Several pathophysiological mechanisms including major role players driving LN have been identified. A large body of literature suggest that prevention of fibrosis—which contributes to chronicity of LN—may significantly improve long-term prognosis. Bone morphogenetic protein-7 (BMP-7) was first identified as a therapeutic option in this context decades ago and evidence of its benefit in various conditions, including LN, is ever-increasing. Despite these facts, BMP-7 is not being implemented as therapy in the context of renal disease. With this review, we briefly summarise current understanding of LN pathology and discuss the evidence in support of therapeutic potential of BMP-7 in this context. Lastly, we address the obstacles that need to be overcome, before BMP-7 may become available as LN treatment.

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Effect of Chronic Dolutegravir Administration on the Trace Amine Profile in Wistar Rats

Henning,

Kellermann,

Smith

2024

Drugs R D

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Alterations to microbial secretome by estrogen may contribute to sex bias in irritable bowel syndrome

Cited by 5 publications

References 79 publications

Aspalathus linearis (Rooibos) and Agmatine May Act Synergistically to Beneficially Modulate Intestinal Tight Junction Integrity and Inflammatory Profile

Aspalathus linearis (Rooibos) and Agmatine May Act Synergistically to Beneficially Modulate Intestinal Tight Junction Integrity and Inflammatory Profile

Potential of bone morphogenetic protein-7 in treatment of lupus nephritis: addressing the hurdles to implementation

Effect of Chronic Dolutegravir Administration on the Trace Amine Profile in Wistar Rats

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