Gut Microbiome in Down Syndrome

Biagi, Elena; Candela, Marco; Centanni, Manuela; Consolandi, Clarissa; Rampelli, Simone; Turroni, Silvia; Severgnini, Marco; Peano, Clelia; Ghezzo, Alessandro; Scurti, Maria; Salvioli, Stefano; Franceschi, Claudio; Brigidi, Patrizia

doi:10.1371/journal.pone.0112023

Cited by 58 publications

(56 citation statements)

References 43 publications

(51 reference statements)

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“…), but most remarkably, it has been found consistently abundant in Down Syndrome (Biagi et al . ) and in children with autism disorder (Williams et al . ; De Angelis et al .…”

Section: Resultsmentioning

confidence: 99%

Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer's disease during lifespan

Bäuerl

Collado

Cuevas

et al. 2018

Letters in Applied Microbiology

185

114

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Alzheimer's disease (AD) is the most common form of dementia and one of the major causes of disability and dependency in older people. Accumulating evidences link gut microbiota with different diseases and its relationship with neurodegenerative diseases is becoming most intriguing. This study was aimed to compare the gut microbiota of transgenic APP/PS1 (TG) mice, a well‐established deterministic mouse model of AD, with their C57BL/6 wild‐type (WT) littermates. Faecal samples were collected from 3‐, 6‐ and 24‐month‐old mice and analysed by pyrosequencing of the V1–V3 region of the bacterial 16S rRNA genes. Bacterial profiles were similar in all young mice (3 months old), and started to diverge so that 6‐month‐old WT and TG mice had different and more diverse microbiota. During ageing, Turicibacteriaceae (typical mice bacterial group) and Rikenellaceae increased in all groups, although total Bacteroidetes remained stable. TG mice were characterized by an increase in Proteobacteria after 6 months, particularly the genus Sutterella (Betaproteobacteria), interestingly also increased in autism disorder. Also, the inflammation related family Erysipelotrichaceae was more abundant in TG mice at 24 months compared to wild‐type control. In summary, AD pathology in mice shifts the gut microbiota towards profiles that share features with autism and inflammatory disorders. Significance and Impact of the Study Alzheimer's disease is a neurodegenerative disease and neuroinflammation in the central nervous system appears to have a pivotal role. Using the transgenic APP/PS1 (TG) mouse model, we successfully characterized how AD pathology shifted gut microbiota composition during ageing towards an inflammation related bacterial profile related to Proteobacteria and Erysipelotrichaceae and suggest that these changes could contribute to disease progression and severity. Microbiota‐targeted interventions could therefore represent a strategy to postpone disease symptoms.

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“…), but most remarkably, it has been found consistently abundant in Down Syndrome (Biagi et al . ) and in children with autism disorder (Williams et al . ; De Angelis et al .…”

Section: Resultsmentioning

confidence: 99%

Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer's disease during lifespan

Bäuerl

Collado

Cuevas

et al. 2018

Letters in Applied Microbiology

185

114

View full text Add to dashboard Cite

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“…It is not known how TNFR2 deficiency impacts A. muciniphilia abundance, but intracellular cross-talk between short-chain fatty acid and sex-hormone signaling and gene regulation is one possibility. Sutterella, also selectively more abundant in male TNFR2 2/2 2D2 mice, has been positively correlated with autism and Down syndrome (84), as well as degradation of secretory IgA (85). In addition to providing a first line of defense against enteric toxins and pathogens, intestinal secretory IgA, promotes Ag clearance, quenches bacterial virulence factors, and changes the composition of the intestinal microbiota (86).…”

Section: Gut Microbiota In Tnfr2mentioning

confidence: 99%

TNFR2 Deficiency Acts in Concert with Gut Microbiota To Precipitate Spontaneous Sex-Biased Central Nervous System Demyelinating Autoimmune Disease

Miller

Bonn

Franklin

et al. 2015

The Journal of Immunology

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TNF-α antagonists provide benefit to patients with inflammatory autoimmune disorders such as Crohn’s disease, rheumatoid arthritis, and ankylosing spondylitis. However, TNF antagonism unexplainably exacerbates CNS autoimmunity, including multiple sclerosis and neuromyelitis optica. The underlying mechanisms remain enigmatic. We demonstrate that TNFR2 deficiency results in female-biased spontaneous autoimmune CNS demyelination in myelin oligodendrocyte glycoprotein–specific 2D2 TCR transgenic mice. Disease in TNFR2−/− 2D2 mice was associated with CNS infiltration of T and B cells as well as increased production of myelin oligodendrocyte glycoprotein–specific IL-17, IFN-γ, and IgG2b. Attenuated disease in TNF−/− 2D2 mice relative to TNFR2−/− 2D2 mice identified distinctive roles for TNFR1 and TNFR2. Oral antibiotic treatment eliminated spontaneous autoimmunity in TNFR2−/− 2D2 mice to suggest role for gut microbiota. Illumina sequencing of fecal 16S rRNA identified a distinct microbiota profile in male TNFR2−/− 2D2 that was associated with disease protection. Akkermansia muciniphila, Sutterella sp., Oscillospira sp., Bacteroides acidifaciens, and Anaeroplasma sp. were selectively more abundant in male TNFR2−/− 2D2 mice. In contrast, Bacteroides sp., Bacteroides uniformis, and Parabacteroides sp. were more abundant in affected female TNFR2−/− 2D2 mice, suggesting a role in disease causation. Overall, TNFR2 blockade appears to disrupt commensal bacteria–host immune symbiosis to reveal autoimmune demyelination in genetically susceptible mice. Under this paradigm, microbes likely contribute to an individual’s response to anti-TNF therapy. This model provides a foundation for host immune–microbiota-directed measures for the prevention and treatment of CNS-demyelinating autoimmune disorders.

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“…Furthermore, Sutterella spp. have been associated with autism, Down syndrome, and metabolic syndrome (Williams et al, 2012; Wang et al, 2013; Biagi et al, 2014; Lim et al, 2016). Half of the children with autism and GI dysfunction were Sutterella -positive with a predominance of either S. wadsworthensis or S. stercoricanis , whereas these species were not detected in the control group with only GI dysfunction (Williams et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Mucosal Prevalence and Interactions with the Epithelium Indicate Commensalism of Sutterella spp.

et al. 2016

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Sutterella species have been frequently associated with human diseases, such as autism, Down syndrome, and inflammatory bowel disease (IBD), but the impact of these bacteria on health still remains unclear. Especially the interactions of Sutterella spp. with the host are largely unknown, despite of the species being highly prevalent. In this study, we addressed the interaction of three known species of Sutterella with the intestinal epithelium and examined their adhesion properties, the effect on intestinal barrier function and the pro-inflammatory capacity in vitro. We also studied the relative abundance and prevalence of the genus Sutterella and Sutterella wadsworthensis in intestinal biopsies of healthy individuals and patients with celiac disease (CeD) or IBD. Our results show that Sutterella spp. are abundant in the duodenum of healthy adults with a decreasing gradient toward the colon. No difference was detected in the prevalence of Sutterella between the pediatric IBD or CeD patients and the healthy controls. Sutterella parvirubra adhered better than the two other Sutterella spp. to differentiated Caco-2 cells and was capable of decreasing the adherence of S. wadsworthensis, which preferably bound to mucus and human extracellular matrix proteins. Furthermore, only S. wadsworthensis induced an interleukin-8 production in enterocytes, which could be due to different lipopolysaccharide structures between the species. However, its pro-inflammatory activity was modest as compared to non-pathogenic Escherichia coli. Sutterella spp. had no effect on the enterocyte monolayer integrity in vitro. Our findings indicate that the members of genus Sutterella are widely prevalent commensals with mild pro-inflammatory capacity in the human gastrointestinal tract and do not contribute significantly to the disrupted epithelial homeostasis associated with microbiota dysbiosis and increase of Proteobacteria. The ability of Sutterella spp. to adhere to intestinal epithelial cells indicate that they may have an immunomodulatory role.

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Gut Microbiome in Down Syndrome

Cited by 58 publications

References 43 publications

Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer's disease during lifespan

Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer's disease during lifespan

TNFR2 Deficiency Acts in Concert with Gut Microbiota To Precipitate Spontaneous Sex-Biased Central Nervous System Demyelinating Autoimmune Disease

Mucosal Prevalence and Interactions with the Epithelium Indicate Commensalism of Sutterella spp.

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