Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites

Guo, Hao; Chou, Wei-Chun; Lai, Yunjia; Liang, Kaixin; Tam, Jason W.; Brickey, W. June; Chen, Liang; Montgomery, Nathan D.; Li, Xin; Bohannon, Lauren; Sung, Anthony D.; Chao, Nelson J.; Peled, Jonathan U.; Gomes, António; Brink, Marcel R.M. van den; French, Matthew J.; Macintyre, Andrew N.; Sempowski, Gregory D.; Tan, Xianming; Sartor, R. Balfour; Lü, Kun; Ting, Jenny P.‐Y.

doi:10.1126/science.aay9097

Cited by 357 publications

(299 citation statements)

References 33 publications

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“…Muribaculaceae is newly named from family S24-7 (phylum Bacteroidetes) and includes versatile microorganisms involved in complex carbohydrate degradation and de ned as the main mucosal sugar utilizers to reduce Clostridiodes di cile colonization [37,38]. Rikenellaceae and Lachnospiraceae, which were increased after cold acclimation in pigs, could also have the potential ability to utilize mucosal sugars and may be associated with the host health [38][39][40][41]. Lachnospiraceae is also an important butyrate producer that impacts colonization resistance through antibiotic expression or intestinal acidi cation and in uence host mucosal immune cells and enterocytes [40].…”

Section: Discussionmentioning

confidence: 99%

Cold Stress Activates the UCP3 Pathway via Gut Microbiota in Piglet

Lan¹,

Zhu²,

Zhang³

et al. 2021

Preprint

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BackgroundThe gut microbiota plays a key role in the host metabolic thermogenesis by activating uncoupling protein 1 (UCP1) and increasing the browning process of white adipose tissue, especially in a cold environment. However, the crosstalk between gut microbiota and pigs, which lack functional UCP1 making them susceptible to cold, has rarely been illustrated. We used male piglets as a model to evaluate the host response to cold stress via the gut microbiota. ResultsWe found that host thermogenesis and insulin resistance with increased serum metabolites, such as glycocholic acid (GCA), glycochenodeoxycholate (GCDCA), and chenodeoxycholate (CDCA), and altered cecal microbiota compositions and functions under cold stress. Using transcriptomics technology, we found that cytochrome P450, family 8, subfamily b, polypeptide 1 (CYP8B1), FXR, FFAR2, and FFAR3, which are related to bile acid and short-chain fatty acid metabolism, increased in the liver under cold stress. In addition, the fat lipolysis genes CLPS, PNLIPRP1, carnitine palmitoyltransferase 1B (CPT1B), and uncoupling protein 3 (UCP3) were significantly increased in the fat of piglets under cold stress. However, microbiota depletion via treatment with mixed antibiotics weakened the effect on the genes CYP8B1, FFAR2, FFAR3, and CPT1B genes, indicating that the gut microbiota plays important roles in the host thermogenesis. ConclusionsOur results demonstrate that the gut microbiota-blood-liver and fat axis may regulate thermogenesis during cold acclimation in piglets.

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Section: Discussionmentioning

confidence: 99%

Cold Stress Activates the UCP3 Pathway via Gut Microbiota in Piglet

Lan¹,

Zhu²,

Zhang³

et al. 2021

Preprint

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“…These results suggest that radiation-induced disruption of the gut flora increases levels of pro-inflammatory cytokines ( Gerassy-Vainberg et al, 2018 ). In other experiments utilizing a TBI mouse model (8.0–9.2 Gy), the role of the microbiome of “elite survivor” mice and its radioprotective effects were explored ( Guo et al, 2020 ). This study is discussed in more detail below.…”

Section: Animal Models Of Radiation Effects On Microbiomementioning

confidence: 99%

Acute Radiation Syndrome and the Microbiome: Impact and Review

et al. 2021

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Study of the human microbiota has been a centuries-long endeavor, but since the inception of the National Institutes of Health (NIH) Human Microbiome Project in 2007, research has greatly expanded, including the space involving radiation injury. As acute radiation syndrome (ARS) is multisystemic, the microbiome niches across all areas of the body may be affected. This review highlights advances in radiation research examining the effect of irradiation on the microbiome and its potential use as a target for medical countermeasures or biodosimetry approaches, or as a medical countermeasure itself. The authors also address animal model considerations for designing studies, and the potential to use the microbiome as a biomarker to assess radiation exposure and predict outcome. Recent research has shown that the microbiome holds enormous potential for mitigation of radiation injury, in the context of both radiotherapy and radiological/nuclear public health emergencies. Gaps still exist, but the field is moving forward with much promise.

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“…However, increased fecal concentrations of microbiota-derived propionate and tryptophan metabolites in elite survivors was observed in the mice study. The administration of these metabolites caused long-term radioprotection, the mitigation of hematopoietic and gastrointestinal syndromes, and a reduction in proinflammatory responses [ 111 ].…”

Section: The Role Of the Gut Microbiota In Brain Development Cognmentioning

confidence: 99%

Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity

Ciernikova

Mego

Chovanec

2021

Cancers

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Chemotherapy, targeting not only malignant but also healthy cells, causes many undesirable side effects in cancer patients. Due to this fact, long-term cancer survivors often suffer from late effects, including cognitive impairment and cardiovascular toxicity. Chemotherapy damages the intestinal mucosa and heavily disrupts the gut ecosystem, leading to gastrointestinal toxicity. Animal models and clinical studies have revealed the associations between intestinal dysbiosis and depression, anxiety, pain, impaired cognitive functions, and cardiovascular diseases. Recently, a possible link between chemotherapy-induced gut microbiota disruption and late effects in cancer survivors has been proposed. In this review, we summarize the current understanding of preclinical and clinical findings regarding the emerging role of the microbiome and the microbiota–gut–brain axis in chemotherapy-related late effects affecting the central nervous system (CNS) and heart functions. Importantly, we provide an overview of clinical trials evaluating the relationship between the gut microbiome and cancer survivorship. Moreover, the beneficial effects of probiotics in experimental models and non-cancer patients with neurocognitive disorders and cardiovascular diseases as well as several studies on microbiota modulations via probiotics or fecal microbiota transplantation in cancer patients are discussed.

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Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites

Cited by 357 publications

References 33 publications

Cold Stress Activates the UCP3 Pathway via Gut Microbiota in Piglet

Cold Stress Activates the UCP3 Pathway via Gut Microbiota in Piglet

Acute Radiation Syndrome and the Microbiome: Impact and Review

Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity

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