Indigenous Microbiota Protects against Inflammation-Induced Osteonecrosis

Williams, D.; Vuong, Helen E.; Kim, S; Lenon, A; Ho, Katie; Hsiao, Elaine Y.; Sung, Eric C.; Kim, R H

doi:10.1177/0022034520908594

Cited by 20 publications

(29 citation statements)

References 40 publications

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“…kV/114 μA), bone loss was measured at six pre-determined anatomical landmarks as previously described (53). The bacterial load was then determined (54).…”

Section: Ligature-induced Periodontitis and Periodontal Bone Lossmentioning

confidence: 99%

Aberrant type 1 immunity drives susceptibility to mucosal fungal infections

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Oikonomou

Dutzan

et al. 2021

Science

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119

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Human monogenic disorders have revealed the critical contribution of type 17 responses in mucosal fungal surveillance. We unexpectedly found that in certain settings, enhanced type 1 immunity rather than defective type 17 responses can promote mucosal fungal infection susceptibility. Notably, in mice and humans with AIRE deficiency, an autoimmune disease characterized by selective susceptibility to mucosal but not systemic fungal infection, mucosal type 17 responses are intact while type 1 responses are exacerbated. These responses promote aberrant interferon-γ (IFN-γ)– and signal transducer and activator of transcription 1 (STAT1)–dependent epithelial barrier defects as well as mucosal fungal infection susceptibility. Concordantly, genetic and pharmacologic inhibition of IFN-γ or Janus kinase (JAK)–STAT signaling ameliorates mucosal fungal disease. Thus, we identify aberrant T cell–dependent, type 1 mucosal inflammation as a critical tissue-specific pathogenic mechanism that promotes mucosal fungal infection susceptibility in mice and humans.

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“…kV/114 μA), bone loss was measured at six pre-determined anatomical landmarks as previously described (53). The bacterial load was then determined (54).…”

Section: Ligature-induced Periodontitis and Periodontal Bone Lossmentioning

confidence: 99%

Aberrant type 1 immunity drives susceptibility to mucosal fungal infections

Break

Oikonomou

Dutzan

et al. 2021

Science

Self Cite

119

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“…In a previous report, it was demonstrated that BPs exerted inhibitory effects on the growth of select bacterial species ( 24 ). Recently, Williams et al demonstrated increased local bacterial infiltration in MRONJ mice ( 25 ). Moreover, after extracting healthy teeth from mice, and following with zoledronate infusions, no differences were observed in the formation of osteonecrosis between mice receiving broad-spectrum antibiotic treatment and negative controls.…”

Section: The Mucosal Immune Response and Mronjmentioning

confidence: 99%

“…Interestingly, antibiotic-mediated oral dysbiosis causes increased bone necrosis when extracting teeth with ligature-induced periodontitis. Moreover, they showed that broad-spectrum antibiotic treatment suppressed the normal flora to protect against inflammation-induced osteonecrosis by dampening the formation of osteonecrosis and by activating osteoclasts ( 25 ). The results showed that the imbalance in oral flora may be a prerequisite for MRONJ and biological barriers are of great necessity to prevent the occurrence of MRONJ ( Figure 1 ).…”

Section: The Mucosal Immune Response and Mronjmentioning

confidence: 99%

The Role of the Immune Response in the Development of Medication-Related Osteonecrosis of the Jaw

et al. 2021

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Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug effect. There are multiple hypotheses to explain the development of MRONJ. Reduced bone remodeling and infection or inflammation are considered central to the pathogenesis of MRONJ. In recent years, increasing evidence has shown that bisphosphonates (BPs)-mediated immunity dysfunction is associated with the pathophysiology of MRONJ. In a healthy state, mucosal immunity provides the first line of protection against pathogens and oral mucosal immune cells defense against potentially invading pathogens by mediating the generation of protective immunoinflammatory responses. In addition, the immune system takes part in the process of bone remodeling and tissue repair. However, the treatment of BPs disturbs the mucosal and osteo immune homeostasis and thus impairs the body's ability to resist infection and repair from injury, thereby adding to the development of MRONJ. Here, we present the current knowledge about immunity dysfunction to shed light on the role of local immune disorder in the development of MRONJ.

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“… 34 The microbiome may further influence host immune responses to inflammation, bacterial infections and wound healing, thus, predisposing or protecting the host to/from this side effect. 35 , 36 …”

Section: Interactions Between the Microbiome And Treatments For Muscumentioning

confidence: 99%

Interactions of the microbiome with pharmacological and non-pharmacological approaches for the management of ageing-related musculoskeletal diseases

Papageorgiou

2021

Therapeutic Advances in Musculoskeletal

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Despite major progress in the understanding of the pathophysiology and therapeutic options for common ageing-related musculoskeletal conditions (i.e. osteoporosis and associated fractures, sarcopenia and osteoarthritis), there is still a considerable proportion of patients who respond sub optimally to available treatments or experience adverse effects. Emerging microbiome research suggests that perturbations in microbial composition, functional and metabolic capacity (i.e. dysbiosis) are associated with intestinal and extra-intestinal disorders including musculoskeletal diseases. Besides its contributions to disease pathogenesis, the role of the microbiome is further extended to shaping individuals’ responses to disease therapeutics (i.e. pharmacomicrobiomics). In this review, we focus on the reciprocal interactions between the microbiome and therapeutics for osteoporosis, sarcopenia and osteoarthritis. Specifically, we identify the effects of therapeutics on microbiome’s configurations, functions and metabolic output, intestinal integrity and immune function, but also the effects of the microbiome on the metabolism of these therapeutics, which in turn, may influence their bioavailability, efficacy and side-effect profile contributing to variable treatment responses in clinical practice. We further discuss emerging strategies for microbiota manipulation as preventive or therapeutic (alone or complementary to available treatments) approaches for improving outcomes of musculoskeletal health and disease.

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Indigenous Microbiota Protects against Inflammation-Induced Osteonecrosis

Cited by 20 publications

References 40 publications

Aberrant type 1 immunity drives susceptibility to mucosal fungal infections

Aberrant type 1 immunity drives susceptibility to mucosal fungal infections

The Role of the Immune Response in the Development of Medication-Related Osteonecrosis of the Jaw

Interactions of the microbiome with pharmacological and non-pharmacological approaches for the management of ageing-related musculoskeletal diseases

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