Gut Microbiota Mediates the Therapeutic Effect of Monoclonal Anti-TLR4 Antibody on Acetaminophen-Induced Acute Liver Injury in Mice

Sun, Xuewei; Cui, Qian; Ni, Juan; Liu, Xiaoguang; Zhu, Jin; Zhou, Tingting; Huang, Huaying; OuYang, Ke; Wu, Yuankui; Yang, Zhan

doi:10.1128/spectrum.00647-22

Cited by 5 publications

(8 citation statements)

References 44 publications

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“…In summary, the results presented by Sun et al ( 1 ) raise serious concerns regarding the data and their interpretation, as no evidence was provided as to how an antibody can survive the digestive tract intact and realistically influence the pathophysiology of APAP hepatotoxicity within a relevant time frame.…”

Section: Lettermentioning

confidence: 98%

“…We read with interest the recent paper by Sun et al ( 1 ) showing that an anti-TLR4 antibody protected against acetaminophen (APAP)-induced liver injury by modulating gut microbiota and gut permeability. At first glance, these results may provide an alternate explanation for the long-term controversy about the role of inflammation in the injury process ( 2 ).…”

Section: Lettermentioning

confidence: 99%

“…The therapeutic window for these highly effective, direct-acting drugs in the mouse model is less than 6 h after treatment with 600 mg/kg of body weight APAP ( 4 , 5 ). The authors now suggest that APAP changes gut microbiota composition and enhances gut permeability, with microbial metabolites contributing to APAP-induced liver injury ( 1 ). Importantly, an anti-TLR4 antibody administered orally 2 h after APAP escapes digestion and prevents these events in the intestine and colon ( 1 ).…”

Section: Lettermentioning

confidence: 99%

“…The authors now suggest that APAP changes gut microbiota composition and enhances gut permeability, with microbial metabolites contributing to APAP-induced liver injury ( 1 ). Importantly, an anti-TLR4 antibody administered orally 2 h after APAP escapes digestion and prevents these events in the intestine and colon ( 1 ). For one, the authors showed changes in gut microbiota and gut permeability at 24 h after APAP, i.e., long after the liver injury has occurred.…”

Section: Lettermentioning

confidence: 99%

“…Third, the authors attempted to mimic the effects of the antibody by using fecal microbiota transplantation for 3 days or short-chain fatty acids treatment for 7 days ( 1 ). Thus, the question arises why these treatments had to be done for several days compared to a single posttreatment with the antibody?…”

Section: Lettermentioning

confidence: 99%

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Putative Effects of an Orally Administered Anti-TLR4 Antibody on Gut Microbiota and Acetaminophen Hepatotoxicity in Mice

Jaeschke

Ramachandran

2023

Microbiol Spectr

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Section: Lettermentioning

confidence: 98%

Section: Lettermentioning

confidence: 99%

Section: Lettermentioning

confidence: 99%

Section: Lettermentioning

confidence: 99%

Section: Lettermentioning

confidence: 99%

See 3 more Smart Citations

Putative Effects of an Orally Administered Anti-TLR4 Antibody on Gut Microbiota and Acetaminophen Hepatotoxicity in Mice

Jaeschke

Ramachandran

2023

Microbiol Spectr

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Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine

Sall,

Foxall,

Felth

et al. 2024

Preprint

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The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance which could be influenced by differences in microbiota, and yet no study has capitalized upon this natural variation to identify specific features linked to tolerance. We leveraged this natural variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar and predictive morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained differences in the development in tolerance. Mice that did not develop tolerance also maintained a higher abundance of taxa capable of producing the short-chain fatty acid (SCFA) butyrate, known to bolster intestinal barriers, suppress inflammation, and promote neuronal homeostasis. Furthermore, dietary butyrate supplementation significantly reduced the development of tolerance. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.

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Targeted modulation of gut microbiota by traditional Chinese medicine and natural products for liver disease therapy

Zhu

Zheng

et al. 2023

Front. Immunol.

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The gut microbiota not only constitutes intestinal microenvironment homeostasis and human health but also exerts indispensable roles in the occurrence and progression of multiple liver diseases, including alcohol-related liver disease, nonalcoholic fatty liver disease, autoimmune liver disease and liver cancer. Given the therapeutic status of these diseases, their prevention and early therapy are crucial, and the detailed mechanism of gut microbiota in liver disease urgently needs to be explored. Meanwhile, multiple studies have shown that various traditional Chinese medicines, such as Si Miao Formula, Jiangzhi Granules, Liushen Capsules, Chaihu-Shugan Power, Cassiae Semen and Gynostemma, as well as some natural products, including Costunolide, Coprinus comatus polysaccharide, Antarctic krill oil, Oridonin and Berberine, can repair liver injury, improve fatty liver, regulate liver immunity, and even inhibit liver cancer through multiple targets, links, and pathways. Intriguingly, the aforementioned effects demonstrated by these traditional Chinese medicines and natural products have been shown to be closely related to the gut microbiota, directly driving the strategy of traditional Chinese medicines and natural products to regulate the gut microbiota as one of the breakthroughs in the treatment of liver diseases. Based on this, this review comprehensively summarizes and discusses the characteristics, functions and potential mechanisms of these medicines targeting gut microbiota during liver disease treatment. Research on the potential effects on gut microbiota and the regulatory mechanisms of traditional Chinese medicine and natural products provides novel insights and significant references for developing liver disease treatment strategies. In parallel, such explorations will enhance the comprehension of traditional Chinese medicine and natural products modulating gut microbiota during disease treatment, thus facilitating their clinical investigation and application.

show abstract

Gut Microbiota Mediates the Therapeutic Effect of Monoclonal Anti-TLR4 Antibody on Acetaminophen-Induced Acute Liver Injury in Mice

Cited by 5 publications

References 44 publications

Putative Effects of an Orally Administered Anti-TLR4 Antibody on Gut Microbiota and Acetaminophen Hepatotoxicity in Mice

Putative Effects of an Orally Administered Anti-TLR4 Antibody on Gut Microbiota and Acetaminophen Hepatotoxicity in Mice

Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine

Targeted modulation of gut microbiota by traditional Chinese medicine and natural products for liver disease therapy

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