Impact of Gut Microbiota on Radiation-Associated Cognitive Dysfunction and Neuroinflammation in Mice

2022 ◽  
Author(s):  
Na Luo ◽  
Wenjun Zhu ◽  
Xiaoyu Li ◽  
Min Fu ◽  
Xiaohong Peng ◽  
...  

Radiation-induced brain injury is a common complication of brain irradiation that eventually leads to irreversible cognitive impairment. Evidence has shown that the gut microbiome may play an important role in radiation-induced cognitive function. However, the effects of gut microbiota on radiation-induced brain injury (RIBI) remain poorly understood. Here we studied the link between intestinal microbes and radiation-induced brain injury to further investigate the effects of intestinal bacteria on neuroinflammation and cognitive function. We first verified the differences in gut microbes between male and female mice and administered antibiotics to C57BL/6 male mice to deplete the gut flora and then expose mice to radiation. We found that depletion of intestinal flora after irradiation may act as a protective modulator against radiation-induced brain injury. Moreover, we found that pretreatment with depleted gut microbes in RIBI mice suppressed brain pro-inflammatory factor production, and high-throughput sequencing analysis of mouse feces at 1-month postirradiation revealed microbial differences. Interestingly, a proportion of Verrucomicrobia Akkermansia showed partial recovery. Additionally, short-chain fatty acid treatments increased neuroinflammation in the radiation-induced brain injury model. Although a further increase in cognitive function was not observed, brain injury was aggravated in whole-brain irradiated mice to some extent. The protective effects of depleted intestinal flora and the utilization of the brain-gut axis open new avenues for development of innovative therapeutic strategies for radiation-induced brain injury.

2021 ◽  
Vol 8 ◽  
Author(s):  
Haigang Wu ◽  
Xian Wu ◽  
Li Huang ◽  
Chongmei Ruan ◽  
Jinni Liu ◽  
...  

The intestinal flora is a micro-ecosystem that is closely linked to the overall health of the host. We examined the diversity and abundance of intestinal microorganisms in mice following the administration of andrographolide, a component of the Chinese medical herb Andrographis paniculata. Administration of andrographolide produces multiple beneficial effects including anti-inflammatory, antiviral and antibacterial effects but whether it directly influences the gut microbiota is not known. This study investigated whether the oral administration of andrographolide influences the intestinal microbiota and was compared with amoxicillin treatment as a positive control and water only as a negative control. We examined 21 cecal samples and conducted a high-throughput sequencing analysis based on V3-V4 variable region of the 16S rDNA genes. We found that the diversity and abundance of mouse gut microbiota decreased in direct proportion with the amoxicillin dose whereas andrographolide administration did not affect intestinal microbial community structure. The composition of intestinal microbes following andrographolide treatment was dominated by the Firmicutes while Bacteroidetes dominated the amoxicillin treatment group compared with the negative controls. Specifically, the f__Lachnospiraceae_ Unclassified, Lachnospiraceae_ NK4A136_group and Ruminococcaceae_ UCG-014 were enriched with andrographolide administration while Bacteroides, Klebsiella and Escherichia-Shigella significantly increased in the amoxicillin test groups. Amoxicillin administration altered the microbial community composition and structure by increasing the proportion of pathogenic to beneficial bacteria whereas andrographolide administration led to increases in the proportions and abundance of beneficial bacteria. This study provides a theoretical basis for finding alternatives to antibiotics to decrease bacterial resistance and restore intestinal floral imbalances.


2016 ◽  
Vol 40 (5) ◽  
pp. E3 ◽  
Author(s):  
Terry C. Burns ◽  
Ahmed J. Awad ◽  
Matthew D. Li ◽  
Gerald A. Grant

Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells. These changes, in combination with a state of chronic neuroinflammation, underlie impairments in memory, attention, executive function, and acquisition of motor and language skills. Animal models of radiation-induced brain injury have demonstrated a robust capacity of both neural stem cells and oligodendrocyte progenitor cells to restore cognitive function after brain irradiation, likely through a combination of cell replacement and trophic effects. Oligodendrocyte progenitor cells exhibit a remarkable capacity to migrate, integrate, and functionally remyelinate damaged white matter tracts in a variety of preclinical models. The authors here critically address the opportunities and challenges in translating regenerative cell therapies from rodents to humans. Although valiant attempts to translate neuroprotective therapies in recent decades have almost uniformly failed, the authors make the case that harnessing human radiation-induced brain injury as a scientific tool represents a unique opportunity to both successfully translate a neuroregenerative therapy and to acquire tools to facilitate future restorative therapies for human traumatic and degenerative diseases of the central nervous system.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wenxia Zhu ◽  
Yilin Wu ◽  
Hui Liu ◽  
Caini Jiang ◽  
Lili Huo

The gut microbiota is an important regulator for maintaining the organ microenvironment through effects on the gut-vital organs axis. Respiratory tract infections are one of the most widespread and harmful diseases, especially in the last 2 years. Many lines of evidence indicate that the gut microbiota and its metabolites can be considered in therapeutic strategies to effectively prevent and treat respiratory diseases. However, due to the different gut microbiota composition in children compared to adults and the dynamic development of the immature immune system, studies on the interaction between children’s intestinal flora and respiratory infections are still lacking. Here, we describe the changes in the gut microbiota of children with respiratory tract infections and explain the relationship between the microbiota of children with their immune function and disease development. In addition, we will provide perspectives on the direct manipulation of intestinal microbes to prevent or treat pediatric respiratory infections.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shanshan Guo ◽  
Wenye Geng ◽  
Shan Chen ◽  
Li Wang ◽  
Xuli Rong ◽  
...  

The effects of ginger on gastrointestinal disorders such as ulcerative colitis have been widely investigated using experimental models; however, the mechanisms underlying its therapeutic actions are still unknown. In this study, we investigated the correlation between the therapeutic effects of ginger and the regulation of the gut microbiota. We used dextran sulfate sodium (DSS) to induce colitis and found that ginger alleviated colitis-associated pathological changes and decreased the mRNA expression levels of interleukin-6 and inducible nitric oxide synthase in mice. 16s rRNA sequencing analysis of the feces samples showed that mice with colitis had an intestinal flora imbalance with lower species diversity and richness. At the phylum level, a higher abundance of pathogenic bacteria, Proteobacteria and firmicutes, were observed; at the genus level, most samples in the model group showed an increase in Lachnospiraceae_NK4A136_group. The overall analysis illustrated an increase in the relative abundance of Lactobacillus_murinus, Lachnospiraceae_bacterium_615, and Ruminiclostridium_sp._KB18. These increased pathogenic bacteria in model mice were decreased when treated with ginger. DSS-treated mice showed a lower abundance of Muribaculaceae, and ginger corrected this disorder. The bacterial community structure of the ginger group analyzed with Alpha and Beta indices was similar to that of the control group. The results also illustrated that altered intestinal microbiomes affected physiological functions and adjusted key metabolic pathways in mice. In conclusion, this research presented that ginger reduced DSS-induced colitis severity and positively regulated the intestinal microbiome. Based on the series of data in this study, we hypothesize that ginger can improve diseases by restoring the diversity and functions of the gut microbiota.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wenzhi Hao ◽  
Jiajia Wu ◽  
Naijun Yuan ◽  
Lian Gong ◽  
Junqing Huang ◽  
...  

Disturbance of the gut microbiota plays an essential role in mental disorders such as depression and anxiety. Xiaoyaosan, a traditional Chinese medicine formula, has a wide therapeutic spectrum and is used especially in the management of depression and anxiety. In this study, we used an antibiotic-induced microbiome-depleted (AIMD) mouse model to determine the possible relationship between imbalance of the intestinal flora and behavioral abnormalities in rodents. We explored the regulatory effect of Xiaoyaosan on the intestinal flora and attempted to elucidate the potential mechanism of behavioral improvement. We screened NLRP3, ASC, and CASPASE-1 as target genes based on the changes in gut microbiota and explored the effect of Xiaoyaosan on the colonic NLRP3 pathway. After Xiaoyaosan intervention, AIMD mice showed a change in body weight and an improvement in depressive and anxious behaviors. Moreover, the gut flora diversity was significantly improved. Xiaoyaosan increased the abundance of Lachnospiraceae in AIMD mice and decreased that of Bacteroidaceae, the main lipopolysaccharide (LPS)-producing bacteria, resulting in decreased levels of LPS in feces, blood, and colon tissue. Moreover, serum levels of the inflammatory factor, IL-1β, and the levels of NLRP3, ASC, and CASPASE-1 mRNA and DNA in the colon were significantly reduced. Therefore, Xiaoyaosan may alleviate anxiety and depression by modulating the gut microbiota, correcting excessive LPS release, and inhibiting the immoderate activation of the NLRP3 inflammasome in the colon.


2019 ◽  
Author(s):  
Jinyue Liu ◽  
Xue Liang ◽  
Yanhua Liu

ABSTRACTIn this paper, 16S-rRNA gene Illumina HiSeq sequencing was used to analyze the structural diversity of captive and wild roe deer gut flora. The results show that the microbial diversity in the feces of wild roe deer is higher than in that of captive roe deer. Both roe deer have similar flora at the phylum level, but the main genus has significant differences. The microbial group that plays an important role in captive roe deer is Bacteroidetes; in wild roe deer it is Firmicutes. This difference is mainly due to the differences in living environment, diet, and physiological functions of the two groups. In conclusion, our study makes people have a better understanding of the intestinal flora of roe deer. By comparing the intestinal microbial structure differences between captive and wild roe deer, it provides theoretical basis for people to raise captive roe deer and provides reference for the protection of wild roe deer.IMPORTANCEMany studies have shown that large and complex microbes in the gut of humans and non-human animals, intestinal microbes are thought to co-evolve with the host, help the host acquire nutrients, regulate immunity and to help maintain host homeostasis. The roe deer (Capreolus spp.) is a ruminant. Wild roe deer are listed on the List of Terrestrial Wild Animals Protected by the State or Have Important Economic and Scientific Values, wild roe deer is also a Chinese national protected animal under second class protection. However, current research on the gut microbiota of roe deer has not been reported.


2020 ◽  
Author(s):  
Qiang Wang ◽  
Chenjun Hao ◽  
Wenchao Yao ◽  
Defu Zhu ◽  
Haifeng Lu ◽  
...  

Abstract Background: The gut microbiota participates in the metabolism of substances and energy, promotes the development and maturation of the immune system, forms the mucosal barrier, and protects the host from pathogen attacks. Although the pathogenesis of cholesterol gallstones is still not clear, studies have suggested that gut microbiota dysbiosis plays an important role in their formation. Methods: Microbial DNA from faeces of normal control patients and those of patients with calculi was subjected to 16S rRNA gene sequencing to detect gene expression changes in intestinal microbes. ELISA kits were used to measure free bile acids, secondary bile acids and coprostanol according to the manufacturer’s instructions. The relationship between flora and their metabolites was then analysed. Results: In the gallstone group, the diversity of intestinal bacteria and the abundances of certain phylogroups were significantly decreased (p<0.05), especially Firmicutes (p<0.05), the largest phylum represented by the gut microbiota. This study found an increase in free bile acids (p<0.001) and secondary bile acids (p<0.01) in the enterohepatic circulation. Bile salt hydrolase activity was not related to the abundances of BSH-active bacteria. 7a-dehydroxylating gut bacteria were significantly increased (p<0.01), whereas cholesterol-lowering bacteria were significantly reduced (p<0.05). The Ruminococcus gnavus group could be used as a biomarker to distinguish the gallstone group from the control group. Conclusion: We conclude that intestinal flora imbalance affects bile acid and cholesterol metabolism and is associated with gallstone formation.


2022 ◽  
Vol 9 ◽  
Author(s):  
Meng Li ◽  
Xiaoming Wang ◽  
Xingjie Lin ◽  
Xiuju Bian ◽  
Rui Jing ◽  
...  

Background: Henoch-Schönlein purpura, now called immunoglobulin A (IgA) vasculitis, is a common autoimmune disease in children, its association with gut microbiota composition remains unknown.Methods: The collected cases were divided into three groups: G1 group of simple skin type, G2 group with no digestive tract expression, G3 group of mixed digestive tract, and C group of healthy children. The fecal samples of each group of children were collected and the sequencing data was processed and analyzed. The dilution curve reflected the reasonableness of the amount of sequencing data.Results: The number of species composition sequences in the G1, G2 and G3 groups was lower than that in the C group, especially for the G2 and G3 groups. The four most abundant bacteria were Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria. The relative abundance of Proteobacteria in the G2 and G3 groups was significantly higher than that in the G1 and C groups, while the relative abundance of Actinobacteria was significantly reduced, and the relative abundance of Actinobacteria in the G1 group was lower than that in the C group. Principal component analysis of the UPGMA clustering tree and each group of samples showed that the microbial community composition of the same group of samples was similar.Conclusions: The abundance of intestinal microbes in children with IgA vasculitis is lower than in normal children. Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria are the four most abundant bacteria in the intestinal flora of children. Proteobacteria and Actinobacteria are associated with organ involvement in IgA vasculitis.


2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Zheng Yuan Su

The gut microbiota plays an important role in the human body, for example, they are responsible for the metabolism of some dietary factors. Many diseases are related to the imbalances in the gut microbiota. Accumulating evidence shows that traditional Chinese medicine herbs may prevent or treat some diseases through interacting with gut microbiota. Oral administration of Chinese herbs may change the composition of intestinal flora, and the ingredients in Chinese herbs can be catalyzed into bioactive metabolites by some intestinal microbes, resulting in their pharmacological effects. However, the interaction between Chinese herbs and gut microbiota remains unclear. One of the main challenges is the complexity and diversity of the components of Chinese herbs and intestinal flora. Recently, the correction among diseases, gut microbiota, and Chinese herbs through many methodologies are studied by using novel methods and techniques, such as high-throughput gene sequencing, real-time quantitative PCR, and metabolomics analysis as well as the multivariate data statistics. In the future, the clarified mechanism will open a new avenue for the prevention or treatment of diseases by taking Chinese herbs which regulate the composition of gut microbiota, which may achieve the goals of the personalized medicine.


Author(s):  
Yongping Jian ◽  
Dan Zhang ◽  
Mingdi Liu ◽  
Yishu Wang ◽  
Zhi-Xiang Xu

Radiotherapy is an important treatment for abdominal tumors. A critical side effect for this therapy is enteritis. In this review, we aim to summarize recent findings in radiation enteritis, in particular the role of gut microbiota dysbiosis in the development and therapy of the disease. Gut microbiota dysbiosis plays an important role in the occurrence of various diseases, such as radiation enteritis. Abdominal radiation results in changes in the composition of microbiota and reduces its diversity, which is mainly reflected in the decrease of Lactobacillus spp. and Bifidobacterium spp. and increase of Escherichia coli and Staphylococcus spp. Gut microbiota dysbiosis aggravates radiation enteritis, weakens intestinal epithelial barrier function, and promotes inflammatory factor expression. Pathogenic Escherichia coli induce the rearrangement and redistribution of claudin-1, occludin, and ZO-1 in tight junctions, a critical component in intestinal epithelial barrier. In view of the role that microbiome plays in radiation enteritis, we believe that intestinal flora could be a potential biomarker for the disease. Correction of microbiome by application of probiotics, fecal microbiota transplantation (FMT), and antibiotics could be an effective method for the prevention and treatment of radiation-induced enteritis.


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