Betaine inhibits Toll-like receptor 4 responses and restores intestinal microbiota in acute liver failure mice

Chen, Qian; Wang, Yao; Jiao, Fangzhou; Shi, Chunxia; Pei, Maohua; Wang, Gaofeng; Gong, Zhengliang

doi:10.1038/s41598-020-78935-6

Cited by 25 publications

(21 citation statements)

References 48 publications

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“…If the barrier is breached, it can cause significant inflammation and, if sustained, liver damage [ 196 ]. Betaine improved the intestinal mucosal barrier by upregulating expression of zonula occludens-1 (ZO1) and occluding-tight junction proteins as well as maintained the normal gut microbiota composition in an acute liver failure model by inhibiting the TLR4/MyD88 signaling pathway [ 197 ]. Similar results were also reported on attenuation of LPS-induced decreases of the tight junction structural proteins, occluding, and claudin-1, by betaine administration to restore barrier function of porcine intestinal epithelial cells [ 198 ].…”

Section: Disease Prevention By Betaine Administrationmentioning

confidence: 99%

Beneficial Effects of Betaine: A Comprehensive Review

Arumugam

Paal

Donohue

et al. 2021

Biology

138

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Medicinal herbs and many food ingredients possess favorable biological properties that contribute to their therapeutic activities. One such natural product is betaine, a stable, nontoxic natural substance that is present in animals, plants, and microorganisms. Betaine is also endogenously synthesized through the metabolism of choline or exogenously consumed through dietary intake. Betaine mainly functions as (i) an osmolyte and (ii) a methyl-group donor. This review describes the major physiological effects of betaine in whole-body health and its ability to protect against both liver- as well as non-liver-related diseases and conditions. Betaine’s role in preventing/attenuating both alcohol-induced and metabolic-associated liver diseases has been well studied and is extensively reviewed here. Several studies show that betaine protects against the development of alcohol-induced hepatic steatosis, apoptosis, and accumulation of damaged proteins. Additionally, it can significantly prevent/attenuate progressive liver injury by preserving gut integrity and adipose function. The protective effects are primarily associated with the regulation of methionine metabolism through removing homocysteine and maintaining cellular SAM:SAH ratios. Similarly, betaine prevents metabolic-associated fatty liver disease and its progression. In addition, betaine has a neuroprotective role, preserves myocardial function, and prevents pancreatic steatosis. Betaine also attenuates oxidant stress, endoplasmic reticulum stress, inflammation, and cancer development. To conclude, betaine exerts significant therapeutic and biological effects that are potentially beneficial for alleviating a diverse number of human diseases and conditions.

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Section: Disease Prevention By Betaine Administrationmentioning

confidence: 99%

Beneficial Effects of Betaine: A Comprehensive Review

Arumugam

Paal

Donohue

et al. 2021

Biology

138

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“…[58] Rat small intestinal cell line IEC-18 3.4 to 6.8 mM for 24 h (in combination with lipopolysaccharide) [59]…”

Section: Summary and Future Workmentioning

confidence: 99%

Betaine in ameliorating alcohol-induced hepatic steatosis

Rehman

Mehta

2021

Eur J Nutr

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Alcohol-associated liver disease (AALD) is one of most common chronic liver diseases. Hepatic steatosis is the earliest stage in AALD pathological spectrum, reversible by alcohol abstinence. Untreated steatosis can progress to steatohepatitis, fibrosis and/or cirrhosis. Considering the difficulties in achieving complete abstinence, challenges in disease reversal at advanced stages, high costs of AALD management and lack of standardised prescribed medications for treatment, it is essential to explore low-cost natural compounds that can target AALD at an early stage and halt or decelerate disease progression. Betaine is a non-hazardous naturally occurring nutrient. Here, we address the mechanisms of alcohol-induced hepatic steatosis, the role of betaine in reversing the effects i.e., its action against hepatic steatosis in animal models and humans, and the associated cellular and molecular processes. Accordingly, the review discusses how betaine restores the alcohol-induced reduction in methylation potential by elevating the levels of S-adenosylmethionine and methionine. It details how betaine reinstates alcohol-induced alterations in the expressions and/or activities of protein phosphtase-2A, FOXO1, PPAR-α, AMPK, SREBP-1c, fatty acid synthase, diacylglycerol transferase-2, adiponectin and nitric oxide. Interrelationships between these factors in preventing de novo lipogenesis, reducing hepatic uptake of adipose-tissue-derived free fatty acids, promoting VLDL synthesis and secretion, and restoring β-oxidation of fatty acids to attenuate hepatic triglyceride accumulation are elaborated. Despite its therapeutic potential, very few clinical trials have examined betaine’s effect on alcohol-induced hepatic lipid accumulation. This review will provide further confidence to conduct randomised control trials to enable maximum utilisation of betaine’s remedial properties to treat alcohol-induced hepatic steatosis.

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“…In female mice exposed in utero to air pollution, the relative abundance of Coriobacteriales was higher. This order is reduced in colitic mice [43] and enriched in acute liver failure [44]. By contrast, Coriobacteriales are more abundant in diseased mucosal ileum tissues from Crohn's disease patients compared to control mucosa from non-IBD patients [45].…”

Section: Discussionmentioning

confidence: 97%

In Utero Exposure to Simulated Complex Urban Air Pollution Disturbs Intestinal Suckling-to-Weaning Transition in Mice

Guilloteau

Coll

et al. 2021

Preprint

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Background Emerging data indicate that prenatal exposure to air pollution may lead to higher susceptibility to several non-communicable diseases. Limited research has been conducted due to difficulties in modelling realistic air pollution exposure. In this study, pregnant mice were exposed from gestational day 10 to 17 to an atmosphere representative of a 2013 pollution event in Beijing, China. Intestinal homeostasis and microbiota were assessed in both male and female offspring during the suckling-to-weaning transition. Results Sex-specific differences were observed in progeny of gestationally-exposed mice. In utero exposed males exhibited decreased villus and crypt length, vacuolation abnormalities, and lower levels of tight junction protein ZO-1 in ileum. They showed an upregulation of absorptive cell markers and a downregulation of neonatal markers in colon. Cecum of in utero exposed male mice also presented a deeply unbalanced inflammatory pattern. By contrast, in utero exposed female mice displayed less severe intestinal alterations, but included dysregulated expression of Lgr5 in colon, Tjp1 in cecum, and Epcam, Car2 and Sis in ileum. Moreover, exposed female mice showed dysbiosis characterized by a decreased weighted UniFrac β-diversity index, a higher abundance of Bacteroidales and Coriobacteriales orders, and a reduced Firmicutes/Bacteroidetes ratio. Conclusion Prenatal realistic modelling of an urban air pollution event induced sex-specific precocious alterations of structural and immune intestinal development in mice.

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Betaine inhibits Toll-like receptor 4 responses and restores intestinal microbiota in acute liver failure mice

Cited by 25 publications

References 48 publications

Beneficial Effects of Betaine: A Comprehensive Review

Beneficial Effects of Betaine: A Comprehensive Review

Betaine in ameliorating alcohol-induced hepatic steatosis

In Utero Exposure to Simulated Complex Urban Air Pollution Disturbs Intestinal Suckling-to-Weaning Transition in Mice

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