The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions

Vindigni, Stephen M.; Zisman, Timothy L.; Suskind, David L.; Damman, Christopher J.

doi:10.1177/1756283x16644242

Cited by 165 publications

(127 citation statements)

References 251 publications

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“…C ). A compromised intestinal barrier in diseases such as IBD has been shown to skew gut inflammation towards a more proinflammatory state . Analyses of colon pro‐ and anti‐inflammatory cytokine expression revealed that increased permeability in the post‐ABX, dysbiotic cohort was accompanied by a trending increase in the TNF:α/IL‐10 ratio (Fig.…”

Section: Resultsmentioning

confidence: 99%

Probiotic Lactobacillus reuteri Prevents Postantibiotic Bone Loss by Reducing Intestinal Dysbiosis and Preventing Barrier Disruption

Schepper

Collins

Rios‐Arce³

et al. 2019

Journal of Bone and Mineral Research

139

154

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Antibiotic treatment, commonly prescribed for bacterial infections, depletes and subsequently causes long‐term alterations in intestinal microbiota composition. Knowing the importance of the microbiome in the regulation of bone density, we investigated the effect of postantibiotic treatment on gut and bone health. Intestinal microbiome repopulation at 4‐weeks postantibiotic treatment resulted in an increase in the Firmicutes:Bacteroidetes ratio, increased intestinal permeability, and notably reduced femoral trabecular bone volume (approximately 30%, p < 0.01). Treatment with a mucus supplement (a high‐molecular‐weight polymer, MDY‐1001 [MDY]) prevented the postantibiotic‐induced barrier break as well as bone loss, indicating a mechanistic link between increased intestinal permeability and bone loss. A link between the microbiome composition and bone density was demonstrated by supplementing the mice with probiotic bacteria. Specifically, Lactobacillus reuteri, but not Lactobacillus rhamnosus GG or nonpathogenic Escherichia coli, reduced the postantibiotic elevation of the Firmicutes:Bacteroidetes ratio and prevented femoral and vertebral trabecular bone loss. Consistent with causing bone loss, postantibiotic‐induced dysbiosis decreased osteoblast and increased osteoclast activities, changes that were prevented by both L. reuteri and MDY. These data underscore the importance of microbial dysbiosis in the regulation of intestinal permeability and bone health, as well as identify L. reuteri and MDY as novel therapies for preventing these adverse effects. © 2018 American Society for Bone and Mineral Research.

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Section: Resultsmentioning

confidence: 99%

Probiotic Lactobacillus reuteri Prevents Postantibiotic Bone Loss by Reducing Intestinal Dysbiosis and Preventing Barrier Disruption

Schepper

Collins

Rios‐Arce³

et al. 2019

Journal of Bone and Mineral Research

139

154

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“…Intestinal barrier disruption and endotoxin leakage into the blood stream are now recognized as important pathogenic events in a number of chronic diseases . Importantly, we recently identified intestinal barrier dysfunction as a key mediator of dysbiosis‐induced bone loss .…”

Section: Resultsmentioning

confidence: 99%

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Schepper

Collins

Rios‐Arce

et al. 2019

Journal of Bone and Mineral Research

123

119

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Glucocorticoids (GCs) are potent immune‐modulating drugs with significant side effects, including glucocorticoid‐induced osteoporosis (GIO). GCs directly induce osteoblast and osteocyte apoptosis but also alter intestinal microbiota composition. Although the gut microbiota is known to contribute to the regulation of bone density, its role in GIO has never been examined. To test this, male C57/Bl6J mice were treated for 8 weeks with GC (prednisolone, GC‐Tx) in the presence or absence of broad‐spectrum antibiotic treatment (ABX) to deplete the microbiota. Long‐term ABX prevented GC‐Tx‐induced trabecular bone loss, showing the requirement of gut microbiota for GIO. Treatment of GC‐Tx mice with a probiotic (Lactobacillus reuteri [LR]) prevented trabecular bone loss. Microbiota analyses indicated that GC‐Tx changed the abundance of Verrucomicobiales and Bacteriodales phyla and random forest analyses indicated significant differences in abundance of Porphyromonadaceae and Clostridiales operational taxonomic units (OTUs) between groups. Furthermore, transplantation of GC‐Tx mouse fecal material into recipient naïve, untreated WT mice caused bone loss, supporting a functional role for microbiota in GIO. We also report that GC caused intestinal barrier breaks, as evidenced by increased serum endotoxin level (2.4‐fold), that were prevented by LR and ABX treatments. Enhancement of barrier function with a mucus supplement prevented both GC‐Tx–induced barrier leakage and trabecular GIO. In bone, treatment with ABX, LR or a mucus supplement reduced GC‐Tx–induced osteoblast and osteocyte apoptosis. GC‐Tx suppression of Wnt10b in bone was restored by the LR and high‐molecular‐weight polymer (MDY) treatments as well as microbiota depletion. Finally, we identified that bone‐specific Wnt10b overexpression prevented GIO. Taken together, our data highlight the previously unappreciated involvement of the gut microbiota and intestinal barrier function in trabecular GIO pathogenesis (including Wnt10b suppression and osteoblast and osteocyte apoptosis) and identify the gut as a novel therapeutic target for preventing GIO. © 2019 American Society for Bone and Mineral Research.

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“…Metagenomics techniques can, in a single run, characterize the genetic material of the host and also of every pathogen present in the sample at the moment of death. Both advantages would be useful for canopic jar analysis, potentially relating organs from the same individual, thanks to genetic profiling, but also in order to screen genetic disorders and pathogens, and even more ambitiously, reconstruct whole microbial communities that live in our body, or microbiome, known to be intimately related with abdomen, neural, inflammatory and immune conditions [66][67][68][69]. Some applied examples: in a confirmation study performed by Shin et al [70] on a 17th century AD Korean Mummy diagnosed with atherosclerotic cardiovascular disease, several risk alleles related with the condition were found, indicating genetic predisposition of the disease.…”

Section: Discussionmentioning

confidence: 99%

Egyptian Canopic Jars at the Crossroad of Medicine and Archaeology: Overview of 100 Years of Research and Future Scientific Expectations

Senti¹,

Habicht²,

Rayo³

et al. 2018

Pathobiology

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Ancient Egyptian human remains have been of interest in the fields of both medical and Egyptological research for decades. However, canopic jar holders for internal organs (liver, lungs, stomach, intestines) of Egyptian mummies appear to be but a very occasional source of data for such investigations. The few medical approaches focusing on the content of these jars are summarized and listed according to pathogens and diseases to give a structured overview of this field of study. An extensive search of the literature has been conducted from different bibliographic databases with a total of n = 26 studies found. The majority of diseases found consisted of infectious diseases and internal medicine conditions such as schistosomiasis or emphysema. These are just 2 examples of many that, instead of primarily affecting bone, muscle or skin, specifically target internal organs. Hence, a better understanding of the evolution of diseases that still affect mankind could be gained. In conclusion, this reassessment shows that canopic jars represent a highly underestimated source for histological, radiological and ancient DNA examination of Ancient Egyptian remains and should, thus, be more and more brought back into the focus of retrospective medical research.

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The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions

Cited by 165 publications

References 251 publications

Probiotic Lactobacillus reuteri Prevents Postantibiotic Bone Loss by Reducing Intestinal Dysbiosis and Preventing Barrier Disruption

Probiotic Lactobacillus reuteri Prevents Postantibiotic Bone Loss by Reducing Intestinal Dysbiosis and Preventing Barrier Disruption

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Egyptian Canopic Jars at the Crossroad of Medicine and Archaeology: Overview of 100 Years of Research and Future Scientific Expectations

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