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Prevotella nigrescens
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Prevotella nigrescens

Prevotella nigrescens is a commensal bacterium commonly found in the oral microbiome, where it coexists with other microbes in a balanced ecosystem. 

However, in a state of dysbiosis, it can transition to a pathogenic role, contributing to periodontal disease and systemic inflammation. Thus, it is a key biomarker for oral and overall health assessment.

What is Prevotella nigrescens?

Prevotella nigrescens is a Gram-negative, strictly anaerobic rod-shaped bacterium belonging to the Bacteroidetes phylum. It is part of the Prevotella genus, a group of bacteria commonly found in the human oral cavity. P. nigrescens is frequently isolated from the gingival crevices and dental plaque as a component of normal oral flora​.

It also inhabits other mucosal sites (upper respiratory, gastrointestinal, and genital tracts) as a commensal organism in healthy individuals​.

In the oral cavity, P. nigrescens plays a dual role. Under normal conditions, it coexists harmoniously with the host and other microbes. However, if the local environment shifts, it has the potential to become pathogenic. This characteristic has caused P. nigrescens to be grouped in the “orange complex” of oral bacteria.

P. nigrescens is closely related to Prevotella intermedia; these two species were historically grouped until being distinguished in the 1990s due to genetic makeup and behavior​ differences. Notably, P. nigrescens tends to be found more often at healthy gingival sites, whereas P. intermedia is more frequently recovered from deeper periodontal pockets​.

This suggests that P. nigrescens might be a less virulent relative, yet it can still contribute to disease under conducive conditions. Indeed, overgrowth of P. nigrescens on tooth surfaces and gum tissues can provoke inflammation leading to gingivitis and periodontitis​.

Beyond the mouth, it has been implicated in some non-oral infections in susceptible individuals​.

Given this spectrum from commensal to pathogen, clinicians are investigating P. nigrescens as an important microbial biomarker of oral and systemic health.

P. nigrescens: A Member of the Orange Complex

P. nigrescens is a member of the orange complex of oral bacteria. 

The orange complex in the subgingival microbiome includes species from the Fusobacterium, Prevotella, and Campylobacter genera, which are often linked to periodontitis. 

These bacteria serve as linking organisms, facilitating the colonization and survival of more aggressive periodontal pathogens, such as those in the red complex (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia). The presence of the orange complex is critical for red complex bacteria to establish themselves in the oral environment.

As a member of the orange complex, P. nigrescens plays a role in bacterial adhesion and biofilm formation, contributing to periodontal disease progression.

Role in the Human Microbiome

Prevotella nigrescens is a normal part of the oral microbiome. It is commonly found in saliva and dental plaque, where it typically coexists harmlessly with other microbes. 

However, in a state of dysbiosis, it can shift toward pathogenic behavior, contributing to periodontal disease by forming biofilms and increasing inflammation. For example, it interacts synergistically with pathogens like Porphyromonas gingivalis, enhancing virulence and tissue destruction. 

In periodontitis, P. nigrescens increases the expression of metalloproteases and a haem ABC transporter, contributing to tissue breakdown and iron acquisition.

This context-dependent role makes P. nigrescens a valuable biomarker, signaling microbial imbalance and potential disease progression.

P. nigrescens as a Biomarker

Prevotella nigrescens is a key biomarker for periodontal disease. High levels may indicate microbial imbalance and potential progression to periodontitis. 

As part of the "orange complex" of periodontal bacteria, its presence in subgingival plaque can aid in diagnosing and monitoring treatment responses. 

Beyond oral health, P. nigrescens has systemic implications. Its DNA has been detected in rheumatoid arthritis patients' synovial fluid and may contribute to chronic inflammatory conditions, including IBD

Elevated P. nigrescens levels can be an early warning of localized and systemic inflammation, making it a valuable tool for clinicians managing periodontal and inflammatory diseases.

Who Should Get Tested?

Testing for Prevotella nigrescens (often as part of a panel of periodontal pathogens) can be considered in several patient groups:

Patients with Oral Health Issues

Anyone with chronic gingivitis, periodontitis, or refractory gum inflammation may benefit from microbial testing. Detecting high P. nigrescens levels can confirm a bacterial etiology for periodontal breakdown and guide targeted therapy​.

For example, a patient with deep periodontal pockets or worsening gingival inflammation despite routine care should consider evaluation for organisms like P. nigrescens.

Individuals with Systemic Inflammatory Conditions

Patients diagnosed with rheumatoid arthritis or other autoimmune diseases, as well as those with IBD, should be assessed for periodontal disease. Given the association and possible bidirectional influence between periodontitis and these conditions, screening their oral microbiome is prudent​.

If P. nigrescens is present in high amounts, it might indicate an oral inflammatory burden contributing to the patient's systemic condition. Managing the patient's periodontal health could potentially ameliorate overall inflammation.

High-Risk Populations (Smokers and Diabetics)

Tobacco smoking and diabetes mellitus significantly increase the risk of periodontal disease. Smokers tend to have an oral microbiome shifted toward more anaerobic bacteria; research shows that smokers harbor a greater abundance of Prevotella species compared to non-smokers​. 

Diabetic patients are more susceptible to periodontitis, especially if glycemic control is poor​.

In these high-risk groups, checking for pathogens like P. nigrescens can identify subclinical dysbiosis. Early intervention (e.g. intensive dental cleanings, smoking cessation support, improved glycemic control) may then prevent progression to overt periodontitis.

Immunocompromised or Medically Complex Patients

Immunosuppressed individuals (such as transplant recipients, uncontrolled HIV infection, or those on chemotherapy) are prone to unusual infections. As an opportunistic pathogen, P. nigrescens can cause infections like aspiration pneumonia or abscesses when host defenses are low​.

If such a patient has oral symptoms or is undergoing invasive dental procedures, testing for anaerobes including P. nigrescens may be warranted. Identifying and treating an overgrowth early can reduce the risk of serious systemic infection. 

Similarly, patients with a history of endocarditis or arterial plaque might be considered for oral pathogen screening, since P. nigrescens has been noted in some studies examining bacteria in atherosclerotic lesions​

Testing Procedure and Interpretation

Generally, microbiome testing involves the analysis of a stool sample to determine the balance of bacteria in the gut. Some companies offer testing of the oral microbiome, and/or the vaginal microbiome.

Samples for microbiome testing can generally be obtained from the comfort of home, although it is essential to follow the instructions provided by the laboratory company. 

What Do High Levels Mean?

High Prevotella nigrescens levels indicate dysbiosis and an increased risk of periodontal disease, as they correlate with gum inflammation, chronic gingivitis, and periodontitis. This bacterium contributes to immune-driven tissue destruction by stimulating pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and promoting biofilm formation. 

Elevated P. nigrescens has systemic implications, with DNA detected in rheumatoid arthritis patients’ synovial fluid and potential links to systemic inflammation

Clinicians should view high levels as a red flag for periodontal infection requiring intervention (scaling, root planing, possible antibiotic therapy) and may warrant collaboration with other healthcare providers for systemic disease management. 

Early detection allows for timely treatment, reducing long-term oral and systemic health risks.

What Do Low Levels Mean?

Low P. nigrescens levels typically indicate a balanced oral microbiome and lower risk of periodontal disease. This bacterium is normally present in small amounts, and its absence is not inherently problematic unless it results from antibiotic overuse, which may disrupt microbial diversity. 

If levels drop following periodontal treatment, it suggests successful intervention and should be maintained with good oral hygiene. However, extremely low levels in patients with ongoing oral disease could indicate an imbalance favoring more virulent pathogens like P. gingivalis

Regular monitoring ensures microbial stability and prevents pathogenic shifts.

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See References

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Cai, Z., Zhu, T., Liu, F., Zhuang, Z., & Zhao, L. (2021). Co-pathogens in Periodontitis and Inflammatory Bowel Disease. Frontiers in Medicine, 8. https://doi.org/10.3389/fmed.2021.723719

Huang, C., Shi, G. Smoking and microbiome in oral, airway, gut and some systemic diseases. J Transl Med 17, 225 (2019). https://doi.org/10.1186/s12967-019-1971-7

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Larsen JM. The immune response to Prevotella bacteria in chronic inflammatory disease. Immunology. 2017 Aug;151(4):363-374. doi: 10.1111/imm.12760. Epub 2017 Jun 20. PMID: 28542929; PMCID: PMC5506432.

Oral Microbiome Test by Bristle Health. (2020). Rupa Health. https://www.rupahealth.com/lab-tests/bristle-health-oral-microbiome-test 

Preshaw PM, Alba AL, Herrera D, Jepsen S, Konstantinidis A, Makrilakis K, Taylor R. Periodontitis and diabetes: a two-way relationship. Diabetologia. 2012 Jan;55(1):21-31. doi: 10.1007/s00125-011-2342-y. Epub 2011 Nov 6. PMID: 22057194; PMCID: PMC3228943

Szafrański SP, Deng ZL, Tomasch J, Jarek M, Bhuju S, Meisinger C, Kühnisch J, Sztajer H, Wagner-Döbler I. Functional biomarkers for chronic periodontitis and insights into the roles of Prevotella nigrescens and Fusobacterium nucleatum; a metatranscriptome analysis. NPJ Biofilms Microbiomes. 2015 Sep 23;1:15017. doi: 10.1038/npjbiofilms.2015.17. PMID: 28721234; PMCID: PMC5515211.

Tadjoedin FM, Masulili SLC, Rizal MI, Kusdhany LS, Turana Y, Ismail RI, Bachtiar BM. The Red and Orange Complex Subgingival Microbiome of Cognitive Impairment and Cognitively Normal Elderly with Periodontitis. Geriatrics (Basel). 2022 Jan 4;7(1):12. doi: 10.3390/geriatrics7010012. PMID: 35076522; PMCID: PMC8788293.

Vaginal BiomeFx by Microbiome Labs. (n.d.). Rupa Health. https://www.rupahealth.com/lab-tests/microbiome-labs-vaginal-biomefx 

Zhang Y, Zhen M, Zhan Y, Song Y, Zhang Q, Wang J. Population-Genomic Insights into Variation in Prevotella intermedia and Prevotella nigrescens Isolates and Its Association with Periodontal Disease. Front Cell Infect Microbiol. 2017 Sep 21;7:409. doi: 10.3389/fcimb.2017.00409. PMID: 28983469; PMCID: PMC5613308.

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