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      Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome.

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          Abstract

          Chronic systemic inflammation contributes to the pathogenesis of many age-related diseases. Although not well understood, alterations in the gut microbiota, or dysbiosis, may be responsible for age-related inflammation.

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          Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians

          Elena Biagi, Lotta Nylund, Marco Candela … (2010)
          Background Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections. Methodology/Principal Findings By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians. Conclusions/Significance We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.
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            Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota

            T. Harach, N. Marungruang, N. Duthilleul … (2017)
            Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.
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              Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut

              Elaine Petrof, Gregory Gloor, Stephen Vanner … (2013)
              Background Fecal bacteriotherapy (‘stool transplant’) can be effective in treating recurrent Clostridium difficile infection, but concerns of donor infection transmission and patient acceptance limit its use. Here we describe the use of a stool substitute preparation, made from purified intestinal bacterial cultures derived from a single healthy donor, to treat recurrent C. difficile infection that had failed repeated standard antibiotics. Thirty-three isolates were recovered from a healthy donor stool sample. Two patients who had failed at least three courses of metronidazole or vancomycin underwent colonoscopy and the mixture was infused throughout the right and mid colon. Pre-treatment and post-treatment stool samples were analyzed by 16 S rRNA gene sequencing using the Ion Torrent platform. Results Both patients were infected with the hyper virulent C. difficile strain, ribotype 078. Following stool substitute treatment, each patient reverted to their normal bowel pattern within 2 to 3 days and remained symptom-free at 6 months. The analysis demonstrated that rRNA sequences found in the stool substitute were rare in the pre-treatment stool samples but constituted over 25% of the sequences up to 6 months after treatment. Conclusion This proof-of-principle study demonstrates that a stool substitute mixture comprising a multi-species community of bacteria is capable of curing antibiotic-resistant C. difficile colitis. This benefit correlates with major changes in stool microbial profile and these changes reflect isolates from the synthetic mixture. Trial registration Clinical trial registration number: CinicalTrials.gov NCT01372943
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                Author and article information

                Journal
                Journal ID (iso-abbrev): Ann. Neurol.
                Title: Annals of neurology
                Publisher: Wiley
                ISSN (Electronic): 1531-8249
                ISSN (Print): 0364-5134
                Publication date (Electronic): Jul 2018
                Volume: 84
                Issue: 1
                Affiliations
                [1 ] Department of Neurology, McGovern Medical School at University of Texas Health Science Center Houston, TX.
                [2 ] Department of Anesthesiology, University of Maryland, Baltimore, MD.
                [3 ] Department of Anesthesiology, Baylor College of Medicine, Houston, TX.
                [4 ] Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX.
                [5 ] Dan L. Duncan Comprehensive Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
                [6 ] Department of Molecular and Cell Biology, Institute of Systems Genomics, University of Connecticut, Storrs, CT.
                Article
                Mid ID: NIHMS964901
                DOI: 10.1002/ana.25250
                PMC ID: 6119509
                PubMed ID: 29733457
                SO-VID: f90fc8f3-3443-485e-995f-d69b9c5a1c34
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