Introduction

Pseudomonadota (formerly known as Proteobacteria) represents one of the most diverse and functionally complex phyla within the human microbiome. Found across multiple anatomical niches, these bacteria play a critical role in host-microbe interactions, ranging from beneficial commensalism to opportunistic pathogenicity. By leveraging metagenomics and shotgun sequencing, scientists are uncovering how the balance of this phylum influences systemic health, inflammatory signaling, and the overall stability of the human gut ecosystem.

Location of Microbe

Gut Ecosystem

Pseudomonadota is a minor but significant component of a healthy gut microbiome. It can be found throughout the gastrointestinal tract, including the stomach, duodenum, ileum, right colon, and rectum, where it contributes to the overall microbial landscape.

Oral Ecosystem

In the oral cavity, Pseudomonadota colonizes the saliva and dental tissues. It is particularly noted for its presence in hard tissues, such as calculus-like deposits at the root apex during endodontic infections.

Nasal and Respiratory Ecosystem

These microbes are present in the nasopharyngeal region and the lower respiratory tract, where they interact with the lung's immune system to help maintain pulmonary homeostasis.

Urinary Ecosystem

Pseudomonadota members are found within the urinary tract, often maintaining low abundance in healthy states but capable of expanding during localized dysbiosis.

Behavior During Dysbiosis

Intestinal Shifts

In the gut, dysbiosis is often marked by an overgrowth of Pseudomonadota, particularly members of the Enterobacteriaceae family. This expansion is associated with a decrease in beneficial obligate anaerobes and butyrate producers, which typically provide colonization resistance against opportunistic pathogens.

Oral and Nasal Alterations

Dysbiosis in the upper airways may manifest as a significant shift in abundance. For instance, in certain systemic health conditions, the nasal cavity may show a higher prevalence of Pseudomonadota pathobionts, while the oral cavity may experience a decrease in overall microbial diversity.

Biliary and Systemic Changes

In the biliary tract, a high abundance of Pseudomonadota is often seen in benign biliary diseases, whereas malignant conditions like cholangiocarcinoma may show a shift toward other phyla, indicating that the phylum's role varies significantly depending on the specific disease context.

Disease Associations

Gut Ecosystem Associations

Clostridioides difficile Infection (CDI)

An increased abundance of Pseudomonadota, particularly within the Burkholderiales order, is associated with CDI. This relationship may be mediated by the reduction of metabolites like 3-hydroxylaurate, which can influence the susceptibility of the colon to infection.

Colorectal Cancer (CRC) and Adenoma

Elevated levels of Pseudomonadota, including Escherichia coli and Klebsiella, are associated with stage III colorectal cancer and advanced adenomas. These shifts are often linked to a reduction in microbial diversity and may contribute to tumor-derived translocation into the bloodstream.

Necrotizing Enterocolitis (NEC)

In preterm neonates, the Pseudomonadota phylum is strongly associated with the development of NEC, often emerging as first colonizers in the absence of mature anaerobic communities.

Oral and Nasal Ecosystem Associations

Sickle Cell Disease (SCD)

Children with SCD exhibit a higher prevalence of Pseudomonadota in the nasal cavity, including pathobionts like Yersinia enterocolitica and Klebsiella pneumoniae, which may increase susceptibility to respiratory infections.

Ischemic Stroke

A decreasing trend in Pseudomonadota abundance in the saliva has been associated with patients suffering from acute ischemic stroke (AIS) and transient ischemic attacks (TIA), potentially reflecting shifts in systemic inflammatory environments.

Other Ecosystem Associations

Biliary Diseases

Pseudomonadota is the dominant phylum (approximately 65%) in individuals with benign biliary diseases, whereas it is less prevalent in those with cholangiocarcinoma, suggesting its use as a potential diagnostic biomarker.

Foods Supporting Healthy Balance

Maintaining a balanced gut ecosystem requires dietary strategies that support the growth of beneficial anaerobes, which in turn keep opportunistic pathogens from the Pseudomonadota phylum in check. Prebiotics and specific dietary extracts have shown promise in this regard.

Research indicates that Maitake mushroom extract, rich in polysaccharides like $\beta$-glucans, can positively modulate a reconstructed human gut microbiota. When combined with probiotics such as Lactiplantibacillus plantarum and Bifidobacterium animalis, it helps foster a tolerogenic microenvironment and increases the production of short-chain fatty acids (SCFAs) like butyrate, propionate, and lactate. These metabolites are essential for maintaining gut barrier integrity and reducing inflammatory signaling.

Additionally, diets rich in diverse fibers support the broader microbial community, preventing the overgrowth of a single phylum and ensuring that the functional potential of the microbiome remains supportive of the host's immune and metabolic health.

Actionable Insights

• Support Anaerobic Bacteria: Incorporate prebiotic-rich foods (such as Maitake mushrooms or fiber-dense vegetables) to encourage the growth of butyrate-producing bacteria, which naturally limit the overgrowth of Pseudomonadota.
• Monitor Antibiotic Use: Be mindful of broad-spectrum antibiotic use, as it can deplete commensal anaerobes and create a niche for antimicrobial-resistant Pseudomonadota to expand.
• Oral Hygiene: Maintain consistent oral care to prevent the formation of complex biofilms and calculus-like deposits where Pseudomonadota can dominate.
• Respiratory Wellness: For individuals with systemic immune challenges (such as SCD), prioritizing respiratory hygiene is critical to manage the prevalence of nasal pathobionts.
• Probiotic Synergy: Consider the use of targeted probiotic consortia, which may help restore microbial diversity and reduce the burden of opportunistic pathogens in the gut.

Conclusion

The impact of Pseudomonadota on human health is highly dependent on the specific strain and the anatomical niche it occupies. In the gut, while generally a minor component, its expansion is often a marker of dysbiosis and is associated with various gastrointestinal and systemic inflammatory conditions. In the oral and nasal cavities, it contributes to the frontline defense but can transition into a pathobiont state during immune dysregulation. Ultimately, the goal is not the eradication of Pseudomonadota, but the maintenance of a diverse and balanced ecosystem where these bacteria exist in harmony with beneficial commensals to support host homeostasis.