Hypothyroidism

[michael edward badolato jr]

 https://doi.org/10.3389/fendo.2022.943408

Jiang W. et al. The relationships between the gut microbiota and its metabolites with thyroid diseases. FrontEndocrinSecGutEndocrin 13 2022:

The association between hypothyroid and microbiota

"...It has been previously suggested that hypothyroidism is often accompanied by impaired gastrointestinal motility, which creates favorable conditions for colonization and overgrowth of intestinal bacteria (22). Overgrown bacteria, in turn, promote the impaired neuromuscular function of the gastrointestinal tract, further exacerbating chronic gastrointestinal symptoms in hypothyroid patients (22). Studies have confirmed that excessive growth of tiny intestinal bacteria occurred in hypothyroid patients, which were found to be inhibited with improvement in gastrointestinal symptoms following antibiotic therapy (23, 24). Therefore, hypothyroidism and microbiota are considered in a reciprocal relationship and that assessing the growth of tiny intestinal bacteria could be instructive in managing hypothyroid patients.

Recently, the intestinal microbiota and thyroid metabolism in hypothyroid patients have also been studied. As previously mentioned, Lactobacillus and Bifidobacterium mixtures did not directly alter the thyroid function compensation in hypothyroid patients but helped prevent fluctuations in serum thyroid hormones (47). A clinical trial found that synbiotics may have beneficial effects on thyroid function in hypothyroid patients. However, the difference was not statistically significant in comparison to the placebo group (70). Furthermore, it has been observed that the microbial composition and function were altered in primary hypothyroidism patients. Veillonella, Paraprevotella, Neisseria, and Rheinheimera can distinguish primary hypothyroidism patients from healthy individuals (25). It is noteworthy that reduced levels of SCFAs, caused by a decrease in SCFA-producing bacteria in the gut of primary hypothyroidism patients, exacerbate the intestinal barrier’s impairment and elevated serum lipopolysaccharide [endotoxin] levels. The authors also confirmed that altered intestinal microbiota promoted hypothyroidism in mice by fecal microbiota transplantation. This is the first report to provide a comprehensive and rigorous demonstration of the causal role of the thyroid and the intestine through clinical cross-sectional studies and animal studies. Subsequently, a cross-sectional study analyzed the microbiota in patients with mild subclinical hypothyroidism treated with or without L-T4, where the dose of L-T4 required to maintain TSH levels and the progression of subclinical hypothyroidism was found associated with gut microbes, which is probably a result of the microbiota influencing L-T4 metabolism (29). These studies strongly supported the correlations between primary hypothyroidism and microbial dysbiosis and are of great significance for subsequent studies on the mechanisms of gut-hypothyroid interactions..."

Hepatology, VOL. 73, NO. 6, 2021 Steatohepatitis/Metabolic Liver Disease
Fructose Promotes Leaky Gut,
Endotoxemia, and Liver Fibrosis Through
Ethanol-Inducible Cytochrome
P450-2E1–Mediated Oxidative
and Nitrative Stress
Young-Eun Cho,1,2* Do-Kyun Kim,3
* Wonhyo Seo,4
Bin Gao,4
Seong-Ho Yoo,5
and Byoung-Joon Song1
Fructose intake is known to induce obesity, insulin resistance, metabolic syndrome, and nonalcoholic fatty liver disease
(NAFLD). We aimed to evaluate the effects of fructose drinking on gut leakiness, endotoxemia, and NAFLD and
study the underlying mechanisms in rats, mice, and T84 colon cells. Levels of ileum junctional proteins, oxidative stress
markers, and apoptosis-related proteins in rodents, T84 colonic cells, and human ileums were determined by immunoblotting, immunoprecipitation, and immunofluorescence analyses. Fructose drinking caused microbiome change, leaky
gut, and hepatic inflammation/fibrosis with increased levels of nitroxidative stress marker proteins cytochrome P450-2E1
(CYP2E1), inducible nitric oxide synthase, and nitrated proteins in small intestine and liver of rodents. Fructose drinking significantly elevated plasma bacterial endotoxin levels, likely resulting from decreased levels of intestinal tight junction (TJ) proteins (zonula occludens 1, occludin, claudin-1, and claudin-4), adherent junction (AJ) proteins (β-catenin
and E-cadherin), and desmosome plakoglobin, along with α-tubulin, in wild-type rodents, but not in fructose-exposed
Cyp2e1-null mice. Consistently, decreased intestinal TJ/AJ proteins and increased hepatic inflammation with fibrosis were observed in autopsied obese people compared to lean individuals. Furthermore, histological and biochemical analyses showed markedly elevated hepatic fibrosis marker proteins in fructose-exposed rats compared to controls.
Immunoprecipitation followed by immunoblot analyses revealed that intestinal TJ proteins were nitrated and ubiquitinated, leading to their decreased levels in fructose-exposed rats. Conclusion: These results showed that fructose intake
causes protein nitration of intestinal TJ and AJ proteins, resulting in increased gut leakiness, endotoxemia, and steatohepatitis with liver fibrosis, at least partly, through a CYP2E1-dependent manner. (Hepatology 2021;73:2180-2195).

Sci Rep. 2018; 8: 6573.

Published online 2018 Apr 26. doi: 10.1038/s41598-018-24833-x

PMCID: PMC5919907

PMID: 29700406

Sub-noxious Intravesical Lipopolysaccharide Triggers Bladder Inflammation and Symptom Onset in A Transgenic Autoimmune Cystitis Model: A MAPP Network Animal Study

Paul Kogan,^#1 Suming Xu,^#1 Yaoqin Wang,^#1 Michael A. O’Donnell,¹ Susan K. Lutgendorf,^1,2,3 Catherine S. Bradley,^1,3 Andrew Schrepf,² Karl J. Kreder,^1,3 and Yi Luo¹

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Abstract

Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) can potentially develop symptom flares after exposure to minor bladder irritants such as subclinical bacterial infection. To reproduce this symptom onset, we intravesically instilled a sub-noxious dose of uropathogenic E. coli component lipopolysaccharide (LPS) in young URO-OVA/OT-I mice, a transgenic autoimmune cystitis model that spontaneously develops bladder inflammation at ≥10 weeks of age. Female URO-OVA/OT-I mice (6-weeks old) were treated intravesically with phosphate-buffered saline (PBS) or PBS containing a sub-noxious dose (1 μg) of LPS. Mice were evaluated for bladder inflammation, pelvic pain, and voiding dysfunction at days 1, 7, and 14 post-treatment. Mice treated with LPS but not PBS developed early bladder inflammation with increased macrophage infiltration. Accordingly, the inflamed bladders expressed increased levels of mRNA for proinflammatory cytokines (IL-1β and IL-6) and pain mediator (substance P precursor). In addition, LPS-treated mice exhibited pelvic pain and voiding dysfunction such as increased urinary frequency and reduced bladder capacity. These functional changes sustained up to day 14 tested. Our results indicate that a single sub-noxious dose of intravesical LPS triggers early bladder inflammation and symptom onset in URO-OVA/OT-I mice, providing a useful model for IC/BPS symptom flare study.