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Establishment and resilience of transplanted gut microbiota in aged mice.

ABSTRACT: The maintenance of healthy and resilient gut microbiota is critical for the life quality and healthspan of the elderly. Fecal microbiota transplantation (FMT) has been increasingly used to restore healthy gut microbiota. We systemically studied the establishment and resilience of transplanted microbiota after autologous versus heterologous FMT in aged recipients. Gut microbiota of aged mice (20 months old) failed to restore their original diversity and composition over 8 weeks via spontaneous recovery after antibiotics treatment; in contrast, FMT using either autologous or heterologous (2 months old from a different vendor) donors facilitated the recovery successfully, established donor-like microbiota states, and affected host gene expression profile. Furthermore, the transplanted microbiota established by heterologous FMT is not resilient during chemical-induced colonic inflammation, in contrast to that of autologous FMT. Our findings highlighted the need to monitor the long-term stability of transplanted gut microbiota and to perform multiple FMT when necessary.

SUBMITTER: Wang Y

PROVIDER: S-EPMC8733228 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Establishment and resilience of transplanted gut microbiota in aged mice.

Wang Ying Y Tang Jinhui J Lv Qingqing Q Tan Yuxiang Y Dong Xiaoxiao X Liu Hongbin H Zhao Nannan N He Zhen Z Kou Yan Y Tan Yan Y Liu Xin-An XA Wang Liping L Liu Yang-Yu YY Dai Lei L

iScience 20211218 1

The maintenance of healthy and resilient gut microbiota is critical for the life quality and healthspan of the elderly. Fecal microbiota transplantation (FMT) has been increasingly used to restore healthy gut microbiota. We systemically studied the establishment and resilience of transplanted microbiota after autologous versus heterologous FMT in aged recipients. Gut microbiota of aged mice (20 months old) failed to restore their original diversity and composition over 8 weeks via spontaneous re ...[more]

PMID: 35024588

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Project description:Hepatobiliary abnormality and metabolic disorders are frequently observed complications in patients with inflammatory bowel diseases (IBD). Given that microbiota dysbiosis is a common pathophysiological feature of both IBD and metabolic diseases, we examined how the IBD-induced dysbiosis affects the host metabolism and contributes to the development of associated metabolic diseases using germ-free (GF) mice transplanted with fecal microbiota of DSS-induced colitis mice. There was no significant change in inflammation or barrier integrity in the gut of GF mice that received microbiota from colitis mice compared to their counterparts that were transplanted with microbiota from non-colitis healthy mice. Interestingly, it was observed that the GF recipients of colitis-induced altered microbiota showed a significant decrease in the weight of adipose tissues including mesenteric, epididymal, subcutaneous, and brown fat without any change in body weight, which was accompanied by abnormalities in adipose tissue functions such as fat storage and adiponectin production. Transplantation of colitis-induced altered microbiota also disrupted hepatic lipid metabolism in the GF recipient mice, which was observed by increases in synthesis and accumulation of cholesterol and bile acids in hepatocytes and a decrease in plasma HDL-cholesterol. Additional observations including elevated plasma levels of insulin, decreased hepatic production of FGF21, and decreased levels of fecal short chain fatty acids (SCFAs) and hepatic expression of SCFA receptors led to a conclusion that the transplantation of the colitis-associated dysbiotic microbiota was causally associated with impairments of insulin action and FGF21-adiponectin axis, possibly due to the low SCFA-producing capacity of the colonized microbiota, leading to metabolic abnormalities including adipose tissue dysfunction and dysregulated hepatic lipid metabolism. Our findings suggest potential mechanisms that explain how colitis-associated gut dysbiosis may contribute to the development of metabolic dysfunctions, which could be applied to clinical practice to improve the efficacy of treatment of IBD patients with comorbid metabolic disorders or vice versa.

Project description:Gut microbiota (GM) dysbiosis has been considered a pathogenic origin of many chronic diseases. In our previous trial, a shift in GM structure caused by a complex fiber-rich diet was associated with the health improvement of obese Prader-Willi syndrome (PWS) children. The pre- and post-intervention GMs (pre- and post-group, respectively) from one child were then transplanted into gnotobiotic mice, which resulted in significantly different physiological phenotypes, each of which was similar to the phenotype of the corresponding GM donor. This study was designed to investigate the miRNA-gene regulatory networks involved in causing these phenotypic differences. Using the post-group as a reference, we systematically identified and annotated the differentially expressed (DE) miRNAs and genes in the colon and liver of the pre-group in the second and fourth weeks after GM inoculation. Most of the significantly enriched GO terms and KEGG pathways were observed in the liver and were in the second week after GM transplantation. We screened 23 key genes along with their 73 miRNA regulators relevant to the host phenotype changes and constructed a network. The network contained 92 miRNA-gene regulation relationships, 51 of which were positive, and 41 of which were negative. Both the colon and liver had upregulated pro-inflammatory genes, and genes involved in fatty acid oxidation, lipolysis, and plasma cholesterol clearance were downregulated in only the liver. These changes were consistent with lipid and cholesterol accumulation in the host and with a high inflammation level. In addition, the colon showed an impacted glucagon-like peptide 1 (GLP-1) signaling pathway, while the liver displayed decreased insulin receptor signaling pathway activity. These molecular changes were mainly found in the second week, 2 weeks before changes in body fat occurred. This time lag indicated that GM dysbiosis might initially induce cholesterol and lipid metabolism-related miRNA and gene expression disorder and then lead to lipid accumulation and obesity development, which implicates a causative role of GM dysbiosis in obesity development rather than a result of obesity. This study provides fundamental molecular information that elucidates how dysbiotic GM increases host inflammation and disturbs host lipid and glucose metabolism.

Dataset Information

Establishment and resilience of transplanted gut microbiota in aged mice.

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Establishment and resilience of transplanted gut microbiota in aged mice.

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