Irradiation-Induced Intestinal Damage Is Recovered by the Indigenous Gut Bacteria Lactobacillus acidophilus

Sittipo, Panida; Pham, Huy Quang; Park, Chang Eon; Kang, Gi-Ung; Zhi, Yong; Ji, Hyun Jung; Jang, A-Yeung; Seo, Ho Seong; Shin, Jae‐Ho; Lee, Yun Kyung

doi:10.3389/fcimb.2020.00415

Cited by 21 publications

(27 citation statements)

References 55 publications

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“…Accounting for compositionality, the unraveling of relevant OTUs uniquely affected by pelvic irradiation in a delayed fashion highlighted members of the Ruminococcaceae family, which were also reported to increase in mice following repeated irradiations, 52 and were even described to be radiation-resistant, together with Lachnospiraceae and Clostridiaceae , following sub-lethal murine exposure. 54 Different responses following irradiation were observed for members belonging to the Lachnospiraceae family, which corresponds with reported cases of intestinal damages. 55 – 57 Within both Ruminococcaceae and Lachnospiraceae families, significant increases were observed in OTUs associated with genera Anaerotruncus as well as Oscillibacter and Clostridium cluster XIVb, being in line with what is reported in irradiated mice and minipigs, respectively.…”

Section: Discussionsupporting

confidence: 64%

Intestinal mucositis precedes dysbiosis in a mouse model for pelvic irradiation

Segers

Mysara

Claesen

et al. 2021

ISME Communications

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Pelvic radiotherapy is known to evoke intestinal mucositis and dysbiosis. Currently, there are no effective therapies available to mitigate these injuries, which is partly due to a lack of insight into the events causing mucositis and dysbiosis. Here, the complex interplay between the murine host and its microbiome following pelvic irradiation was mapped by characterizing intestinal mucositis along with extensive 16S microbial profiling. We demonstrated important morphological and inflammatory implications within one day after exposure, thereby impairing intestinal functionality and inducing translocation of intraluminal bacteria into mesenteric lymph nodes as innovatively quantified by flow cytometry. Concurrent 16S microbial profiling revealed a delayed impact of pelvic irradiation on beta diversity. Analysis of composition of microbiomes identified biomarkers for pelvic irradiation. Among them, members of the families Ruminococcaceae, Lachnospiraceae and Porphyromonadaceae were differentially affected. Altogether, our unprecedented findings showed how pelvic irradiation evoked structural and functional changes in the intestine, which secondarily resulted in a microbiome shift. Therefore, the presented in vivo irradiation-gut-microbiome platform allows further research into the pathobiology of pelvic irradiation-induced intestinal mucositis and resultant dysbiosis, as well as the exploration of mitigating treatments including drugs and food supplements.

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Section: Discussionsupporting

confidence: 64%

Intestinal mucositis precedes dysbiosis in a mouse model for pelvic irradiation

Segers

Mysara

Claesen

et al. 2021

ISME Communications

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“…Past studies have revealed that gut microbiota can improve the survival of experimental animals exposed to lethal radiation [ 90 , 91 , 92 , 93 , 94 ] by virtue of their ability to produce short-chain fatty acids and various tryptophan metabolites. We did not evaluate the alterations in gut microbiota in the present study.…”

Section: Discussionmentioning

confidence: 99%

Gamma-Linolenic Acid (GLA) Protects against Ionizing Radiation-Induced Damage: An In Vitro and In Vivo Study

Rengachar

Bhatt

Polavarapu³

et al. 2022

Biomolecules

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Radiation is pro-inflammatory in nature in view of its ability to induce the generation of reactive oxygen species (ROS), cytokines, chemokines, and growth factors with associated inflammatory cells. Cells are efficient in repairing radiation-induced DNA damage; however, exactly how this happens is not clear. In the present study, GLA reduced DNA damage (as evidenced by micronuclei formation) and enhanced metabolic viability, which led to an increase in the number of surviving RAW 264.7 cells in vitro by reducing ROS generation, and restoring the activities of desaturases, COX-1, COX-2, and 5-LOX enzymes, TNF-α/TGF-β, NF-kB/IkB, and Bcl-2/Bax ratios, and iNOS, AIM-2, and caspases 1 and 3, to near normal. These in vitro beneficial actions were confirmed by in vivo studies, which revealed that the survival of female C57BL/6J mice exposed to lethal radiation (survival~20%) is significantly enhanced (to ~80%) by GLA treatment by restoring altered levels of duodenal HMGB1, IL-6, TNF-α, and IL-10 concentrations, as well as the expression of NF-kB, IkB, Bcl-2, Bax, delta-6-desaturase, COX-2, and 5-LOX genes, and pro- and anti-oxidant enzymes (SOD, catalase, glutathione), to near normal. These in vitro and in vivo studies suggest that GLA protects cells/tissues from lethal doses of radiation by producing appropriate changes in inflammation and its resolution in a timely fashion.

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“…Of note, Sittipo et al . have revealed dynamic changes in the prevalence of Lactobacillus species in murine stool samples after irradiation exposure using 16S rRNA-based oligotyping analysis ( 85 ) and reported the contribution of L. acidophilus to functional recovery of radiation-induced epithelial injury both in vitro and in vivo . Treatment of irradiated IOs with HK L. acidophilus can significantly enhance the organoid formation capacity with goblet cell enrichment, suggesting that administration of L. acidophilus and its derivatives might be beneficial to restoring intestinal homeostasis and barrier function impeded by pathogenic bacterial infection or irradiation.…”

Section: Culturing Ios With Microorganisms To Study Host-microbiome I...mentioning

confidence: 99%

Intestinal organoids as advanced modeling platforms to study the role of host-microbiome interaction in homeostasis and disease

Ahn¹,

Kang²,

Seo³

et al. 2022

BMB Rep

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After birth, animals are colonized by a diverse community of microorganisms. The digestive tract is known to contain the largest number of microbiome in the body. With emergence of the gut-brain axis, the importance of gut microbiome and its metabolites in host health has been extensively studied in recent years. The establishment of organoid culture systems has contributed to studying intestinal pathophysiology by replacing current limited models. Owing to their architectural and functional complexity similar to a real organ, co-culture of intestinal organoids with gut microbiome can provide mechanistic insights into the detrimental role of pathobiont and the homeostatic function of commensal symbiont. Here organoid-based bacterial co-culture techniques for modeling host-microbe interactions are reviewed. This review also summarizes representative studies that explore impact of enteric microorganisms on intestinal organoids to provide a better understanding of host-microbe interaction in the context of homeostasis and disease.

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Irradiation-Induced Intestinal Damage Is Recovered by the Indigenous Gut Bacteria Lactobacillus acidophilus

Cited by 21 publications

References 55 publications

Intestinal mucositis precedes dysbiosis in a mouse model for pelvic irradiation

Intestinal mucositis precedes dysbiosis in a mouse model for pelvic irradiation

Gamma-Linolenic Acid (GLA) Protects against Ionizing Radiation-Induced Damage: An In Vitro and In Vivo Study

Intestinal organoids as advanced modeling platforms to study the role of host-microbiome interaction in homeostasis and disease

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