Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice

Zhang, Xue Song; Yin, Yue; Wang, Jincheng; Battaglia, Thomas; Krautkramer, Kimberly A.; Li, Jingyi Jessica; Li, Jackie; Brown, Mark R.; Zhang, Meifan; Badri, Michelle; Armstrong, Abigail J. S.; Strauch, Christopher M.; Wang, Zeneng; Nemet, Ina; Altomare, Nicole; Devlin, Joseph C.; He, Linchen; Morton, Jamie; Chalk, John Alex; Needles, Kelly; Liao, Viviane; Mount, Julia; Li, Huilin; Ruggles, Kelly V.; Bonneau, Richard; Domínguez-Bello, María Gloria; Bäckhed, Fredrik; Hazen, Stanley L.; Blaser, Martin J.

doi:10.1016/j.chom.2021.06.014

Cited by 39 publications

(30 citation statements)

References 131 publications

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“… 101 It was also recently shown that transfer of maternal cecal contents into antibiotic treated pups restored global ileal epithelial miRNA expression profiles including miRNAs that target microbiota-sensitive genes involved in regulating innate and adaptive immunity such as CD44, Tlr2, and Reg3g. 44 Taken together, these studies indicate that further investigation into miRNA regulation by the microbiota has the potential to expand our understanding of microbiota-induced control of host physiology and disease beyond epigenetic regulation of histones and the DNA.…”

Section: Non-covalent Modificationsmentioning

confidence: 91%

“… 20 A recent study also showed that cecal microbiota transfer from dams to pups exposed to antibiotics early in life restored histone modifications in the ileum and liver. 44 Specifically, this microbiota-transfer led to lysine 27 (K27) deacetylation and trimethylation, potentially through enhanced Jumanji family-related lysine demethylase D3 (Jmjd3/Kdm6b) activity in response to Tlr2 induction, indicating that microbiota prevents expression of antibiotic-induced genes. In the intestinal epithelium, differential H3K4me3, a histone methylation associated with active transcription, was also identified at genes in ileal IECs from GF compared to CNV mice, a subset of which overlapped with H3K4me3 profiles unique to newly diagnosed IBD patients compared to healthy controls.…”

Section: Host–microbiota Interactions Through Histone Modificationsmentioning

confidence: 99%

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Epigenetic regulation by gut microbiota

2022

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The gastrointestinal tract is continuously exposed to trillions of commensal microbes, collectively termed the microbiota, which are environmental stimuli that can direct health and disease within the host. In addition to well-established bacterial sensing pathways, microbial signals are also integrated through epigenetic modifications that calibrate the transcriptional program of host cells without altering the underlying genetic code. Microbiota-sensitive epigenetic changes include modifications to the DNA or histones, as well as regulation of non-coding RNAs. While microbiota-sensitive epigenetic mechanisms have been described in both local intestinal cells and as well in peripheral tissues, further research is required to fully decipher the complex relationship between the host and microbiota. This Review highlights current understandings of epigenetic regulation by gut microbiota and important implications of these findings in guiding therapeutic approaches to prevent or combat diseases driven by impaired microbiota-host interactions.

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Section: Non-covalent Modificationsmentioning

confidence: 91%

Section: Host–microbiota Interactions Through Histone Modificationsmentioning

confidence: 99%

Epigenetic regulation by gut microbiota

2022

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“…Transplanting fecal samples from diabetes-protected MyD88deficient NOD mice to wild type female NOD/LtJ mice led to a delayed onset of diabetes and a reduced insulitis (119). Early-life antibiotic exposure not only perturbed the intestinal microbiota, but also accelerated the development of T1DM in the NOD mouse model; however, maternal cecal microbiota transfer to antibiotic-induced NOD mice restored the enhanced disease risk to baseline levels (232,233). A randomized controlled trial published in 2021 found that FMT halted the onset of T1DM in human (234).…”

Section: Fecal Microbiota Transplantationmentioning

confidence: 99%

Gut Dysbiosis in Pancreatic Diseases: A Causative Factor and a Novel Therapeutic Target

et al. 2022

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Pancreatic-related disorders such as pancreatitis, pancreatic cancer, and type 1 diabetes mellitus (T1DM) impose a substantial challenge to human health and wellbeing. Even though our understanding of the initiation and progression of pancreatic diseases has broadened over time, no effective therapeutics is yet available for these disorders. Mounting evidence suggests that gut dysbiosis is closely related to human health and disease, and pancreatic diseases are no exception. Now much effort is under way to explore the correlation and eventually potential causation between the gut microbiome and the course of pancreatic diseases, as well as to develop novel preventive and/or therapeutic strategies of targeted microbiome modulation by probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT) for these multifactorial disorders. Attempts to dissect the intestinal microbial landscape and its metabolic profile might enable deep insight into a holistic picture of these complex conditions. This article aims to review the subtle yet intimate nexus loop between the gut microbiome and pancreatic diseases, with a particular focus on current evidence supporting the feasibility of preventing and controlling pancreatic diseases via microbiome-based therapeutics and therapies.

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“…Uric acid metabolism is typical in diabetic patients ( Sharaf El Din et al., 2017 ); high uric acid levels can increase their risk of cardiovascular and renal complications ( Soltani et al., 2013 ; Xu et al., 2013 ) and aggravate insulin resistance ( Hu et al., 2021 ). The gut microbiota is not only significantly related to diabetes but also its cause ( Vangipurapu et al., 2020 ; Zhang et al., 2021 ). The gut microbiota participates in purine and uric acid metabolism ( Henson, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Variation of Serum Uric Acid Is Associated With Gut Microbiota in Patients With Diabetes Mellitus

Zhang

Wang

Guo

et al. 2022

Front. Cell. Infect. Microbiol.

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Diabetes mellitus is a metabolic disease closely related to a disordered gut microbiome. Diabetic patients usually suffer from various metabolic disorders, such as increased serum uric acid levels. Although serum uric acid levels depend partially on intestine excretion, the relationship between uric acid and gut microbiome in diabetic patients remains unknown. We collected a total of 126 fecal samples from diabetic patients for 16S ribosomal RNA gene amplicon sequencing and recorded clinical data. We analyzed the correlation between clinical indicators and gut microbiota of diabetic patients using Spearman analysis. Since uric acid was the most prominent one, we classified diabetic patients based on their uric acid levels to find the microbiome associated with uric acid disturbance. We constructed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway profiles using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to identify variations between the different groups. Among all the clinical indicators, uric acid had the strongest correlation with gut microbiota. First, we divided the patients into three groups according to their uric acid levels. The two low uric acid groups were similar, while the elevated uric acid group had significant differences in gut microbiota and metabolic pathways. The elevated uric acid group had a significantly lower gut microbiota diversity. At the genus level, this group had remarkably higher Escherichia–Shigella amounts and notably lower Faecalibacterium, Oscillospiraceae_UCG−002, and Oscillospiraceae_UCG−005 amounts. The gut microbiota of the high uric acid group was predicted to be enriched in metabolism, human diseases, and lipopolysaccharide biosynthesis. Since the two low uric acid groups were similar, we regrouped and matched the abnormal uric acid patients with normal uric acid patients. The differences in gut microbiota and metabolic pathways related to nucleotide metabolism became more significant. The serum uric acid levels were associated with gut microbiome changes. This might be related to uric acid metabolism by gut microbes. Our study indicates that targeting the gut microbiome could help manage elevated uric acid levels.

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Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice

Cited by 39 publications

References 131 publications

Epigenetic regulation by gut microbiota

Epigenetic regulation by gut microbiota

Gut Dysbiosis in Pancreatic Diseases: A Causative Factor and a Novel Therapeutic Target

Variation of Serum Uric Acid Is Associated With Gut Microbiota in Patients With Diabetes Mellitus

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