scholarly journals Low-Intensity Exercise Modulates Gut Microbiota to Fight Against Radiation-Induced Gut Toxicity in Mouse Models

Author(s):  
Bin Wang ◽  
Yu-xiao Jin ◽  
Jia-li Dong ◽  
Hui-wen Xiao ◽  
Shu-qin Zhang ◽  
...  

Radiation-induced gastrointestinal (GI) tract toxicity halts radiotherapy and degrades the prognosis of cancer patients. Physical activity defined as “any bodily movement produced by skeletal muscle that requires energy expenditure” is a beneficial lifestyle modification for health. Here, we investigate whether walking, a low-intensity form of exercise, could alleviate intestinal radiation injury. Short-term (15 days) walking protected against radiation-induced GI tract toxicity in both male and female mice, as judged by longer colons, denser intestinal villi, more goblet cells, and lower expression of inflammation-related genes in the small intestines. High-throughput sequencing and untargeted metabolomics analysis showed that walking restructured the gut microbiota configuration, such as elevated Akkermansia muciniphila, and reprogramed the gut metabolome of irradiated mice. Deletion of gut flora erased the radioprotection of walking, and the abdomen local irradiated recipients who received fecal microbiome from donors with walking treatment exhibited milder intestinal toxicity. Oral gavage of A. muciniphila mitigated the radiation-induced GI tract injury. Importantly, walking did not change the tumor growth after radiotherapy. Together, our findings provide novel insights into walking and underpin that walking is a safe and effective form to protect against GI syndrome of patients with radiotherapy without financial burden in a preclinical setting.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vorthon Sawaswong ◽  
Kesmanee Praianantathavorn ◽  
Prangwalai Chanchaem ◽  
Ariya Khamwut ◽  
Taratorn Kemthong ◽  
...  

AbstractLong-tailed macaques (Macaca fascicularis), distributed in Southeast Asia, are generally used in biomedical research. At present, the expansion of human communities overlapping of macaques’ natural habitat causes human-macaque conflicts. To mitigate this problem in Thailand, the National Primate Research Center of Thailand, Chulalongkorn University (NPRCT-CU), was granted the permit to catch the surplus wild-born macaques and transfer them to the center. Based on the fact that the diets provided and the captive environments were different, their oral-gut microbiota should be altered. Thus, we investigated and compared the oral and fecal microbiome between wild-born macaques that lived in the natural habitats and those transferred to and reared in the NPRCT-CU for 1 year. The results from 16S rRNA high-throughput sequencing showed that the captive macaques had distinct oral-gut microbiota profiles and lower bacterial richness compared to those in wild macaques. The gut of wild macaques was dominated by Firmicutes which is probably associated with lipid absorption and storage. These results implicated the effects of captivity conditions on the microbiome that might contribute to crucial metabolic functions. Our study should be applied to the animal health care program, with respect to microbial functions, for non-human primates.


Author(s):  
Molly C. Carney ◽  
Xiang Zhan ◽  
Akanksha Rangnekar ◽  
Maria Z. Chroneos ◽  
Sarah J.C. Craig ◽  
...  

Abstract Rapid infant growth increases the risk for adult obesity. The gut microbiome is associated with early weight status; however, no study has examined how interactions between microbial and host ribonucleic acid (RNA) expression influence infant growth. We hypothesized that dynamics in infant stool micro-ribonucleic acids (miRNAs) would be associated with both microbial activity and infant growth via putative metabolic targets. Stool was collected twice from 30 full-term infants, at 1 month and again between 6 and 12 months. Stool RNA were measured with high-throughput sequencing and aligned to human and microbial databases. Infant growth was measured by weight-for-length z-score at birth and 12 months. Increased RNA transcriptional activity of Clostridia (R = 0.55; Adj p = 3.7E-2) and Burkholderia (R = −0.820, Adj p = 2.62E-3) were associated with infant growth. Of the 25 human RNAs associated with growth, 16 were miRNAs. The miRNAs demonstrated significant target enrichment (Adj p < 0.05) for four metabolic pathways. There were four associations between growth-related miRNAs and growth-related phyla. We have shown that longitudinal trends in gut microbiota activity and human miRNA levels are associated with infant growth and the metabolic targets of miRNAs suggest these molecules may regulate the biosynthetic landscape of the gut and influence microbial activity.


Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Dieter M. Tourlousse ◽  
Koji Narita ◽  
Takamasa Miura ◽  
Mitsuo Sakamoto ◽  
Akiko Ohashi ◽  
...  

Abstract Background Validation and standardization of methodologies for microbial community measurements by high-throughput sequencing are needed to support human microbiome research and its industrialization. This study set out to establish standards-based solutions to improve the accuracy and reproducibility of metagenomics-based microbiome profiling of human fecal samples. Results In the first phase, we performed a head-to-head comparison of a wide range of protocols for DNA extraction and sequencing library construction using defined mock communities, to identify performant protocols and pinpoint sources of inaccuracy in quantification. In the second phase, we validated performant protocols with respect to their variability of measurement results within a single laboratory (that is, intermediate precision) as well as interlaboratory transferability and reproducibility through an industry-based collaborative study. We further ascertained the performance of our recommended protocols in the context of a community-wide interlaboratory study (that is, the MOSAIC Standards Challenge). Finally, we defined performance metrics to provide best practice guidance for improving measurement consistency across methods and laboratories. Conclusions The validated protocols and methodological guidance for DNA extraction and library construction provided in this study expand current best practices for metagenomic analyses of human fecal microbiota. Uptake of our protocols and guidelines will improve the accuracy and comparability of metagenomics-based studies of the human microbiome, thereby facilitating development and commercialization of human microbiome-based products.


2021 ◽  
Vol 17 ◽  
pp. 117693432199635
Author(s):  
Daoxin Liu ◽  
Pengfei Song ◽  
Jingyan Yan ◽  
Haijing Wang ◽  
Zhenyuan Cai ◽  
...  

Wild-caught animals must cope with drastic lifestyle and dietary changes after being induced to captivity. How the gut microbiome structure of these animals will change in response receives increasing attention. The plateau zokor ( Eospalax baileyi), a typic subterranean rodent endemic to the Qinghai-Tibet plateau, spends almost the whole life underground and is well adapted to the environmental pressures of both plateau and underground. However, how the gut microbiome of the plateau zokor will change in response to captivity has not been reported to date. This study compared the microbial community structure and functions of 22 plateau zokors before (the WS group) and after being kept in captivity for 15 days (the LS group, fed on carrots) using the 16S rRNA gene via high-throughput sequencing technology. The results showed that the LS group retained 973 of the 977 operational taxonomic units (OTUs) in the WS group, and no new OTUs were found in the LS group. The dominant bacterial phyla were Bacteroides and Firmicutes in both groups. In alpha diversity analysis, the Shannon, Sobs, and ACE indexes of the LS group were significantly lower than those of the WS group. A remarkable difference ( P < 0.01) between groups was also detected in beta diversity analysis. The UPGMA clustering, NMDS, PCoA, and Anosim results all showed that the intergroup difference was significantly greater than the intragroup difference. And compared with the WS group, the intragroup difference of the gut microbiota in the LS group was much larger, which failed to support the assumption that similar diets should drive convergence of gut microbial communities. PICRUSt revealed that although some functional categories displayed significant differences between groups, the relative abundances of these categories were very close in both groups. Based on all the results, we conclude that as plateau zokors enter captivity for a short time, although the relative abundances of different gut microbiota categories shifted significantly, they can maintain almost all the OTUs and the functions of the gut microbiota in the wild. So, the use of wild-caught plateau zokors in gut microbial studies is acceptable if the time in captivity is short.


2009 ◽  
Vol 136 (2) ◽  
pp. 722-724 ◽  
Author(s):  
Christopher J. Damman ◽  
Christina M. Surawicz

2017 ◽  
Vol 312 (4) ◽  
pp. G327-G339 ◽  
Author(s):  
Rebecca L. Knoll ◽  
Kristoffer Forslund ◽  
Jens Roat Kultima ◽  
Claudius U. Meyer ◽  
Ulrike Kullmer ◽  
...  

Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn’s disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U-test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii, were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option. NEW & NOTEWORTHY In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD.


Author(s):  
Harold J. Boutte ◽  
Jacqueline Chen ◽  
Todd N. Wylie ◽  
Kristine M. Wylie ◽  
Yan Xie ◽  
...  

Background & Aims: Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to two years to determine which patients will wean from PN. Here we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Methods: Stool and sera were collected from healthy controls and from SBS patients (n=52) with ileostomy, jejunostomy, ileocolonic and jejunocolonic anastomoses fed with PN plus enteral nutrition or who were exclusively enterally fed. We undertook 16S rRNA gene sequencing, BA profiling and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS, and serum amino acid analyses. Results: SBS patients exhibited altered gut microbiota with reduced gut microbial diversity compared to healthy controls. We observed differences in the microbiomes of SBS patients with ileostomy vs. jejunostomy, jejunocolonic vs. ileocolonic anastomoses, and PN-dependence compared to those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in SBS patients, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who weaned from PN were enriched in secondary BAs including deoxycholic acid and lithocholic acid. Conclusions: Shifts in gut microbiota and BA metabolites may generate a favorable luminal environment in select SBS patients, promoting the ability to wean from PN. Pro-adaptive microbial species and select BA may provide novel targets for patient-specific therapies for SBS.


2020 ◽  
Vol 6 (1) ◽  
pp. eaax6208 ◽  
Author(s):  
Su-Ling Zeng ◽  
Shang-Zhen Li ◽  
Ping-Ting Xiao ◽  
Yuan-Yuan Cai ◽  
Chu Chu ◽  
...  

Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)–induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.


Animals ◽  
2022 ◽  
Vol 12 (2) ◽  
pp. 145
Author(s):  
Małgorzata Gieryńska ◽  
Lidia Szulc-Dąbrowska ◽  
Justyna Struzik ◽  
Matylda Barbara Mielcarska ◽  
Karolina Paulina Gregorczyk-Zboroch

The gastrointestinal tract, which is constantly exposed to a multitude of stimuli, is considered responsible for maintaining the homeostasis of the host. It is inhabited by billions of microorganisms, the gut microbiota, which form a mutualistic relationship with the host. Although the microbiota is generally recognized as beneficial, at the same time, together with pathogens, they are a permanent threat to the host. Various populations of epithelial cells provide the first line of chemical and physical defense against external factors acting as the interface between luminal microorganisms and immunocompetent cells in lamina propria. In this review, we focus on some essential, innate mechanisms protecting mucosal integrity, thus responsible for maintaining intestine homeostasis. The characteristics of decisive cell populations involved in maintaining the barrier arrangement, based on mucus secretion, formation of intercellular junctions as well as production of antimicrobial peptides, responsible for shaping the gut microbiota, are presented. We emphasize the importance of cross-talk between gut microbiota and epithelial cells as a factor vital for the maintenance of the homeostasis of the GI tract. Finally, we discuss how the imbalance of these regulations leads to the compromised barrier integrity and dysbiosis considered to contribute to inflammatory disorders and metabolic diseases.


2021 ◽  
Author(s):  
Irene Maier ◽  
Paul M Ruegger ◽  
Julia Deutschmann ◽  
Thomas H. Helbich ◽  
Peter Pietschmann ◽  
...  

Microbiota can both negatively and positively impact radiation-induced bone loss. Our prior research showed that compared to mice with conventional gut microbiota (CM), mice with restricted gut microbiota (RM) reduced inflammatory tumor necrosis factor (TNF) in bone marrow, interleukin (IL)-17 in blood, and chemokine (C-C motif) ligand 20 (CCL20) in bone marrow under anti-IL-17 treatment. We showed that Muribaculum intestinale was more abundant in intestinal epithelial cells (IECs) from the small intestine of female RM mice and positively associated with augmented skeletal bone structure. Female C57BL/6J pun RM mice, which were injected with anti-IL-17 antibody one day before exposure to 1.5 Gy 28Si ions of 850 MeV/u, showed high trabecular numbers in tibiae at 6 weeks postirradiation. Irradiated CM mice were investigated for lower interferon-γ and IL-17 levels in the small intestine than RM mice. IL-17 blockage resulted in bacterial indicator phylotypes being different between both microbiota groups before and after irradiation. Analysis of the fecal bacteria were performed in relation to bone quality and body weight, showing reduced tibia cortical thickness in irradiated CM mice (–15%) vs. irradiated RM mice (–9.2%). Correlation analyses identified relationships among trabecular bone parameters (TRI-BV/TV, Tb.N, Tb.Th, Tb.Sp) and Bacteroides massiliensis, Muribaculum sp. and Prevotella denticola. Turicibacter sp. was found directly correlated with trabecular separation in anti-IL-17 treated mice, whereas an unidentified Bacteroidetes correlated with trabecular thickness in anti-IL-17 neutralized and radiation-exposed mice. We demonstrated radiation-induced osteolytic damage to correlate with bacterial indicator phylotypes of the intestinal microbiota composition, and these relationships were determined from the previously discovered dose-dependent particle radiation effects on cell proliferation in bone tissue. New translational approaches were designed to investigate dynamic changes of gut microbiota in correlation with conditions of treatment and disease as well as mechanisms of systemic side-effects in radiotherapy.


Sign in / Sign up

Export Citation Format

Share Document