Human Microbiome Functions in the Skin Lung and Brain

Introduction to Extraintestinal Microbial Ecosystems

For decades, human microbiology and infectious disease paradigms operated under the assumption that the internal milieu of the healthy human body was largely sterile, with microbial colonization restricted exclusively to the gastrointestinal tract, the oral cavity, the upper respiratory tract, and the epidermal surface ¹². Advanced culture-independent sequencing technologies, specifically 16S ribosomal RNA (rRNA) amplicon sequencing and whole-genome shotgun metagenomics, have fundamentally dismantled this binary perspective of sterility versus infection ¹³⁴. It is now established that the human holobiont functions as an interconnected superorganism, where localized microbial communities exert profound systemic effects on distal organs through highly coordinated neural, immune, and metabolic pathways ⁵⁵⁶.

While the gastrointestinal tract harbors the highest density and diversity of microorganisms - predominantly dominated by the phyla Bacteroidota, Firmicutes, Actinomycetota, and Proteobacteria - recent research has aggressively shifted focus toward peripheral and extraintestinal microbiomes ⁷. These include the distinct, low-biomass microbial communities residing in the lower respiratory tract and the highly topographical ecosystems of the skin ¹⁸. Concurrently, the scientific community is re-evaluating the boundaries of microbial colonization, engaging in rigorous methodological debates regarding the presence of microbes in highly protected, historically sterile environments such as the brain, the placenta, and the intratumoral microenvironment ⁹¹¹¹².

The physiological influence of the microbiome extends far beyond local tissue homeostasis. Through the systemic circulation of microbial metabolites, most notably short-chain fatty acids (SCFAs) like butyrate, propionate, and acetate, and the direct stimulation of the peripheral nervous system, the microbiome continuously orchestrates host immunity, barrier integrity, and neurological function ⁵¹⁰¹¹. This research report provides a comprehensive analysis of the contemporary science surrounding the human microbiome beyond the gut, detailing the specific compositional dynamics of the oral, skin, and lung microbiomes, the mechanisms underpinning the gut-brain axis, and the critical methodological advancements addressing the low-biomass contamination debate.

The Oral Microbiome and Systemic Translocation

The oral cavity represents the second most diverse microbial habitat in the human body, serving as the primary gateway to both the gastrointestinal and respiratory tracts ¹³²¹. The Human Oral Microbiome Database (HOMD) has cataloged over 700 distinct bacterial species belonging to 13 major phyla, with Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes constituting the overwhelming majority of the oral biomass ⁴¹³¹⁴. Facultative anaerobic bacteria, such as those belonging to the genera Streptococcus and Actinomyces, predominate in highly oxygenated areas, whereas the low oxygen tension of the subgingival crevices creates a favorable niche for strict anaerobes, including Bacteroidaceae and Spirochaetes ²¹²².

The oral microbiome does not exist in isolation; it is a critical source of microbial seeding for distal organs. In healthy individuals, the continuous production of saliva and the mechanical action of swallowing transport vast quantities of oral microbes into the gastrointestinal tract ¹⁴²². While the highly acidic environment of the stomach normally eradicates the majority of these bacteria, conditions that elevate gastric pH, such as achlorhydria or the chronic use of proton pump inhibitors, compromise this barrier. This disruption allows oral pathogens, including Klebsiella species and Porphyromonas gingivalis, to translocate and colonize the intestinal mucosa, a phenomenon increasingly linked to the pathogenesis of inflammatory bowel disease (IBD) ¹³.

Furthermore, the oral cavity serves as the primary reservoir for the lung microbiome. Through the physiological process of subclinical micro-aspiration, oropharyngeal secretions containing diverse microbial communities are continuously introduced into the lower respiratory tract ¹²³. Consequently, dysbiosis in the oral cavity - often manifesting as severe periodontitis or rampant dental caries - directly alters the microbial inoculum reaching the lungs, thereby escalating the risk of severe lower respiratory tract infections and exacerbations of chronic pulmonary diseases ²¹²⁸.

The Skin Microbiome and Barrier Immunity

The skin is the largest organ of the human body, functioning as the primary physical, chemical, and immunological barrier against external environmental threats ⁸. It harbors a diverse, topographically distinct microbiome comprising bacteria, fungi, viruses, and mites ¹⁵. Unlike the gut microbiome, which is heavily influenced by dietary substrates, the composition of the cutaneous microbiome is rigidly dictated by localized physiological conditions, including sebum production, eccrine and apocrine gland density, superficial temperature, pH, and moisture levels ⁸²⁴.

Topographical Variations in Cutaneous Microbes

The human epidermis is ecologically partitioned into three primary microenvironments: sebaceous, moist, and dry, each selecting for specific microbial consortia ⁸. Sebaceous sites, which include the face, chest, and back, are characterized by high lipid content and lower oxygen tension within the pilosebaceous units. These regions are predominantly colonized by lipophilic microorganisms, most notably Cutibacterium acnes and fungi of the genus Malassezia ⁸¹⁶.

Moist sites, encompassing the axillae, groin, and the flexural creases of the elbows and knees, maintain higher local humidity and temperature. These specific niches favor the proliferation of Staphylococcus species and Corynebacterium species ⁸²⁵. Conversely, dry sites, such as the volar forearms and the lower legs, experience greater temperature fluctuations and lower hydration. These areas host the greatest overall diversity of microbial species, characterized by a notable prevalence of Streptococcus, Micrococcus, and various Gram-negative bacteria ⁸²⁵. This rigid topographical specialization implies that standardizing a single definitive profile for a healthy skin microbiome is biologically inaccurate; dermatological health is instead defined by the localized ecological stability of these distinct micro-communities ²⁴.

Indigenous Populations and Cutaneous Microbial Diversity

Current understandings of the healthy human skin microbiome have historically been skewed by an immense overrepresentation of genomic data derived from Western, industrialized populations ¹⁶²⁶. In these industrialized cohorts, the skin microbiome typically exhibits remarkably low microbial complexity, heavily dominated by Cutibacterium and Malassezia species ¹⁶. However, recent comparative metagenomic studies involving remote indigenous communities have revealed that modern industrialization corresponds with a severe, systemic depletion of human microbial diversity ²⁷.

A landmark 2025 investigation evaluating the Yanomami people - a remote hunter-gatherer and horticulturalist community in the Amazon basin minimally exposed to industrialization, modern sanitation practices, and antibiotics - uncovered the highest degree of skin bacterial and genetic diversity ever recorded in human populations ¹⁶²⁸. Researchers identified 115 previously unreported bacterial genomes on Yanomami skin ¹⁶²⁶. Compared to Western subjects, the Yanomami adult skin communities were significantly richer, demonstrating an 80% increase in microbial richness and vastly more diverse taxonomic representation, showing much less structural dominance by Cutibacterium species even in highly sebaceous zones ²⁶.

Crucially, the study demonstrated the rapid plasticity of the skin microbiome in response to environmental immersion. When a researcher of Western upbringing immersed himself in the Yanomami lifestyle, his skin microbiome experienced an immediate increase in complexity, structurally mirroring the indigenous microbial richness within weeks. Upon his return to an industrialized setting, this acquired diversity rapidly plummeted, shedding the majority of its newly acquired environmental complexity ¹⁶²⁹. This phenomenon underscores the emerging hypothesis that routine, direct exposure to natural environments, soil substrates, and diverse plant life is essential for maintaining a robust skin microbiome. The widespread loss of this environmental interface in Western populations may be a central contributing factor to the rising epidemiological incidence of chronic inflammatory skin conditions, including atopic dermatitis and psoriasis ²⁷²⁸²⁹.

Cutaneous Immune Modulation and Metabolite Signaling

Skin commensals are active participants in the host's innate and adaptive immune defenses. They achieve this immunomodulation through the competitive exclusion of invasive pathogens, the secretion of antimicrobial peptides, and the production of bioactive metabolites that regulate keratinocyte function ¹⁵²⁴.

Staphylococcus epidermidis, a ubiquitous skin commensal, demonstrates profound immunomodulatory capabilities. It produces bacteriocins and specific modulins that directly target and inhibit the colonization and biofilm formation of pathogenic Staphylococcus aureus ³⁰. Furthermore, S. epidermidis ferments cutaneous glycerol to produce short-chain fatty acids, primarily lactic acid, which serve to maintain the acidic pH of the stratum corneum and promote the expression of tight junction proteins, thereby reinforcing structural barrier integrity ³⁰³¹.

Cutibacterium acnes exhibits a dual physiological role depending heavily on the specific phylotype and the local microenvironmental context. While it is a foundational component of the sebaceous microbiome, localized dysbiosis can trigger its pathogenic potential. Certain phylotypes of C. acnes secrete lipases that hydrolyze sebum triglycerides into free fatty acids. While these fatty acids possess baseline antimicrobial properties against competing species, their excessive accumulation disrupts the epidermal barrier and triggers severe localized inflammation ¹⁵. Furthermore, pathogenic strains of C. acnes produce high levels of porphyrins. Upon exposure to ultraviolet radiation, these microbial porphyrins generate reactive oxygen species, leading to acute oxidative stress and the activation of inflammatory cascades via toll-like receptors on host keratinocytes ⁶¹⁵.

The Gut-Skin Axis in Dermatological Pathology

Dermatological health is not solely dependent on the localized cutaneous microbiome; it is heavily influenced by the gastrointestinal microbiome through the bidirectional "gut-skin axis" ¹⁰³². Dysbiosis in the gut microbiota, characterized by a loss of microbial diversity and increased intestinal permeability, is frequently observed in patients presenting with chronic inflammatory skin diseases ⁶.

The primary mechanism of communication along this physiological axis is metabolic. Dietary fibers fermented by gut microbiota yield systemic SCFAs, predominantly acetate, propionate, and butyrate. These gut-derived SCFAs enter the systemic circulation and exert distant anti-inflammatory and homeostatic effects on the skin ⁶¹⁰. Upon reaching the cutaneous capillary networks, circulating SCFAs bind to G protein-coupled receptors (GPCRs), such as FFAR2 and FFAR3, which are heavily expressed on dermal immune cells and epidermal keratinocytes ¹⁰. This biochemical binding inhibits histone deacetylases, consequently downregulating the NF-κB signaling pathway and sharply reducing the expression of pro-inflammatory cytokines, including IL-1β and TNF-α ⁶¹⁰. Furthermore, SCFAs promote the differentiation and peripheral expansion of regulatory T cells (Tregs), which are critical for maintaining baseline immune tolerance and preventing autoimmune hyper-reactivity in the skin ⁶³⁰³³.

The Lung Microbiome and Respiratory Immunology

Historically, the medical and microbiological communities adhered to the "sterile lung dogma," postulating that the lower respiratory tract was completely devoid of microbial life in healthy individuals, and that the mere presence of bacteria indicated an active clinical infection ¹²³⁴. This paradigm was fundamentally flawed, built entirely upon the limitations of traditional, culture-dependent techniques that failed to identify the vast majority of obligate anaerobes and slow-growing microbial taxa ¹³⁴.

Refutation of the Sterile Lung Paradigm

The widespread application of 16S rRNA gene sequencing and shotgun metagenomics to bronchoalveolar lavage fluid unequivocally demonstrated the existence of a distinct, albeit low-biomass, lung microbiome in healthy human subjects ¹²³⁴. Unlike the densely populated gastrointestinal tract, the healthy human lung contains a relatively sparse population of only $10^{3}$ to $10^{5}$ bacteria per gram of tissue ¹.

The taxonomic composition of the lung microbiome is intimately related to the oral microbiome, heavily dominated by the phyla Bacteroidetes, Firmicutes, and Proteobacteria, with prevalent genera including Prevotella, Streptococcus, and Veillonella ¹². The ecological dynamics of the lung are governed not by static colonization, but by a continuous, dynamic equilibrium between microbial immigration and elimination ¹³⁵. Microbes continuously immigrate into the lower airways primarily through the subclinical micro-aspiration of oropharyngeal secretions, a natural physiological process ¹²³. Simultaneously, these microbes are actively eliminated by mechanical mucociliary clearance, the phagocytic activity of alveolar macrophages, and the inherent antimicrobial properties of pulmonary surfactant ¹¹⁷.

When this delicate equilibrium is disrupted - either by impaired clearance mechanisms, altered environmental conditions such as smoking or hypoxia, or overwhelming microbial immigration - pulmonary dysbiosis rapidly ensues. Dysbiosis in the respiratory tract is characterized by a severe reduction in overall microbial diversity and a significant, pathological increase in total bacterial burden, often accompanied by the aggressive dominance of specific pathobionts ³³⁴. In progressive fibrotic and obstructive diseases, such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease (COPD), an increased bacterial DNA burden in the lower airways serves as a direct, independent predictor of disease progression, exacerbation frequency, and overall mortality ³³⁴.

Causal Evidence from Mendelian Randomization

While observational studies consistently identify lung dysbiosis in chronic respiratory diseases, establishing a definitive causal link between microbiome composition and lung pathology has historically been challenging due to pervasive confounding factors, including concurrent medication use, smoking history, and environmental exposures ³⁶³⁷³⁸. To rigorously bypass these epidemiological limitations, researchers have recently employed bidirectional two-sample Mendelian randomization (MR) analyses. MR utilizes single nucleotide polymorphisms as instrumental variables to infer direct causality, relying on the fundamental genetic principle that variants are randomly assorted during meiosis and are therefore entirely independent of environmental confounders ³⁶³⁷.

Recent large-scale MR studies utilizing expansive Genome-Wide Association Study data have provided robust genetic evidence that specific gut and oral microbial taxa directly influence the pathophysiological risk of chronic respiratory diseases:

These genetically driven analyses confirm that the systemic relationships between distant microbiomes and lung health are not merely associative artifacts, but involve direct, actionable mechanistic pathways ³⁶³⁹.

Mechanisms of the Gut-Lung Axis

The complex communication network facilitating these distant causal effects is defined as the gut-lung axis ⁵⁴²⁴³. The gut microbiota conditions the pulmonary immune environment predominantly through the systemic dissemination of its metabolic products, particularly SCFAs and polyamines, and via neural signaling pathways ⁵⁴⁴.

SCFAs synthesized in the colon traverse the intestinal epithelium into the portal and systemic circulation, eventually reaching the bone marrow. Within the bone marrow compartment, SCFAs act directly on hematopoietic precursor cells, fundamentally altering their developmental trajectory. They promote the generation of heavily primed, yet tolerogenic, innate immune cells - such as macrophages and dendritic cells - which subsequently migrate through the vasculature to the lungs ⁴²⁴⁵. Once resident in the pulmonary tissue, these gut-conditioned immune cells exhibit an enhanced, highly calibrated ability to resolve airway inflammation and clear respiratory pathogens without triggering excessive collateral tissue damage ⁴².

Furthermore, the gut-lung axis plays a critical, foundational role in host defense against severe viral respiratory infections, including influenza, respiratory syncytial virus, and SARS-CoV-2 ⁴⁵⁴⁶. An intact, highly diverse gut microbiome establishes a preemptive antiviral state in the lungs by maintaining basal levels of type I interferons ⁴⁵⁴⁷. Disruption of the gut microbiota via the administration of broad-spectrum antibiotics severely blunts this essential interferon signaling, resulting in delayed viral clearance, unrestrained viral replication, and exacerbated pulmonary immunopathology ⁴⁷⁴⁸. Experimental murine models have demonstrated that repairing the gut microbiome through fecal microbiota transplantation or the administration of specific precision probiotics can rapidly restore pulmonary antiviral immunity and rescue hosts from otherwise lethal respiratory infections ⁴⁵⁴⁶.

The Gut-Brain Axis and Neurological Regulation

The conceptualization of the microbiota-gut-brain axis represents one of the most profound paradigm shifts in contemporary neuroscience ¹¹³²⁴⁹. The gastrointestinal tract and the central nervous system maintain a constant, bidirectional dialogue that regulates not only basic digestive homeostasis but also higher-order cognitive function, stress resilience, emotional regulation, and neuroinflammation ⁵⁰⁵¹⁵².

Because the blood-brain barrier strictly regulates the entry of cells and large macromolecules into the central nervous system, intact bacteria do not naturally colonize the healthy brain. Instead, the gut microbiome asserts its profound neurological influence remotely, utilizing three primary physiological conduits: neural pathways, endocrine signaling, and the systemic circulation of immunomodulatory metabolites ⁴⁹⁵¹⁵³.

Enteric-Central Neural Communication

The most direct and rapid line of communication between the gut and the brain is the vagus nerve, the principal component of the parasympathetic nervous system ¹¹⁵¹⁵³. The vagus nerve comprises approximately 80% sensory afferent fibers and 20% motor efferent fibers, effectively acting as an extensive, highly sensitive sensory apparatus that continuously monitors the luminal environment of the gastrointestinal tract ⁵³.

Because vagal afferent terminals do not physically cross the intestinal epithelial lining, they rely entirely on specialized intermediary cells to relay microbial signals. Enterochromaffin cells, which reside scattered throughout the gut epithelium, synthesize over 90% of the body's total serotonin ¹¹. The synthesis and release of serotonin by these cells are heavily dependent on the presence of the gut microbiome and its specific metabolic byproducts ¹¹⁴⁹. Once released into the lamina propria, gut-derived serotonin binds to specialized 5-HT3 receptors located on adjacent vagal afferent nerve fibers ¹¹. This biochemical binding generates rapid action potentials that travel up the vagus nerve to the brainstem, specifically terminating in the nucleus tractus solitarius ¹¹. From the nucleus tractus solitarius, these neural signals are relayed to higher brain centers, including the dorsal raphe nucleus and the locus coeruleus, ultimately exerting profound influence over mood, anxiety, and complex behavioral responses ¹¹.

Experimental models utilizing germ-free mice provide dramatic, unambiguous evidence for this exact pathway. Germ-free mice exhibit significantly reduced baseline vagal nerve activity. However, when specific microbiome-derived metabolites - such as SCFAs and secondary bile acids - are introduced into the intestinal lumen, vagal nerve firing is rapidly and robustly restored ⁵⁹. This confirms that microbial metabolites function as direct chemosensory triggers for ascending gut-brain neural signaling ⁵³⁵⁹.

Endocrine Signaling and the Stress Response

Beyond the direct neural pathways of the vagus nerve, the gut microbiome interacts continuously with the hypothalamic-pituitary-adrenal axis, the body's primary neuroendocrine stress response system ⁴⁹⁵⁰⁵². Commensal microbes actively modulate the physiological threshold of HPA axis activation. In states of severe gut dysbiosis, increased intestinal permeability permits the pathological translocation of bacterial lipopolysaccharides into the systemic circulation ⁴⁹⁵⁴.

The presence of systemic lipopolysaccharides triggers an aggressive peripheral immune response, causing the massive release of pro-inflammatory cytokines that can subsequently cross the blood-brain barrier or interact directly with its endothelial cells. This cascade initiates deep neuroinflammation, stimulates the HPA axis to release excessive circulating cortisol, and is strongly, mechanistically implicated in the pathogenesis of major depressive disorder, severe anxiety, and accelerated age-related cognitive decline ⁴⁹⁵⁵.

Microbial Metabolites in Neuroinflammation

While the vagus nerve handles rapid electrochemical signaling, circulating microbial metabolites provide sustained, long-term biochemical regulation of the central nervous system ⁴⁹⁵⁵. Short-chain fatty acids, particularly butyrate, cross the intestinal barrier and enter systemic circulation. While only a minute fraction of systemic SCFAs actually crosses the blood-brain barrier, their peripheral and vascular effects are neurologically profound ⁴⁹⁵³.

SCFAs actively maintain the structural integrity of both the gut-blood barrier and the blood-brain barrier by upregulating the genetic expression of crucial tight junction proteins, such as claudins and occludins ⁴⁹⁵³. A structurally compromised blood-brain barrier allows neurotoxic substances and peripheral inflammatory cytokines to seep into the brain parenchyma, where they rapidly activate microglia - the primary resident immune cells of the central nervous system ⁵³⁵⁵. Chronic, unresolved microglial activation leads to sustained neuroinflammation, a universal hallmark feature of debilitating neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis ³²⁵⁵. By fortifying vascular barrier integrity and suppressing baseline peripheral inflammation, a diverse, SCFA-producing gut microbiome acts as a vital, highly effective neuroprotective buffer ³²⁵⁰⁵³.

The Low-Biomass Sequencing Contamination Debate

As next-generation genomic sequencing technologies became exponentially more sensitive over the last decade, researchers began reporting the discovery of distinct microbial communities in biological niches previously considered entirely sterile. Between 2014 and 2020, high-profile publications claimed to definitively identify resident microbiomes within the human placenta, the brain parenchyma, the blood, and the deep intratumoral microenvironment ^9121856. These claims suggested revolutionary, paradigm-shifting implications for understanding fetal development, neurobiology, and oncology ⁵⁷⁵⁸.

However, the broader scientific community has recently subjected these extraordinary claims to intense, highly critical methodological scrutiny. This re-evaluation has definitively revealed that the vast majority of signals derived from these "low-biomass" environments are heavily confounded by external contamination, rather than representing genuine, viable symbiotic microbiomes ^911245960.

Methodological Challenges in Tissue Sequencing

The fundamental, pervasive issue in low-biomass microbiome research is the severe distortion of the signal-to-noise ratio ⁵⁹⁶¹. In high-biomass samples like feces or dental plaque, the sheer absolute abundance of microbial DNA entirely overwhelms any minor environmental contamination introduced during processing. However, in tissues like the brain or placenta, the absolute quantity of endogenous microbial DNA - if any exists at all - is exceptionally low. Consequently, the vast majority of extracted genetic material is human host DNA ⁹.

When researchers blindly amplify and sequence these samples, they amplify whatever trace microbial DNA is present, regardless of its origin. This fundamental dynamic introduces two critical sources of false positives: 1. The "Kitome" and "Splashome": Commercial DNA extraction kits, PCR reagents, and ambient laboratory environments are not entirely free of microbial DNA ⁹²⁴⁵⁸. The complex manufacturing processes of these biological reagents often leave trace amounts of highly fragmented bacterial DNA. In low-biomass samples, this ubiquitous background contamination (colloquially termed the "kitome") is heavily amplified and erroneously reported as a resident tissue microbiome ²⁴. 2. Host DNA Misclassification: In bulk tissue sequencing, over 99.9% of the resulting genomic reads may originate from the human host ⁹. Bioinformatics pipelines mapping these reads to bacterial reference databases occasionally misclassify short fragments of human DNA as microbial due to homologous sequences or algorithmic mapping errors, thereby generating entirely artificial false-positive microbial profiles ⁹.

Genomic DNA Fragment Length Analysis

To conclusively resolve these deep controversies, recent landmark methodological studies - including a highly influential 2025/2026 methodology published in Nature - have established genomic DNA fragment length as a definitive, highly reliable metric for quality control in low-biomass environments ¹⁸¹⁹.

The underlying premise of this methodology is strictly biological: if a human tissue harbors a genuine, living microbiome, the resident microbes must contain intact, full-length genomes. Consequently, when DNA is extracted using careful, high-fidelity techniques (e.g., long-read sequencing technologies like Oxford Nanopore), the resulting microbial DNA fragments should be long and relatively intact ¹⁹. Conversely, if the detected microbial signal originates from degraded laboratory reagents or environmental dust, the DNA will have severely degraded over time, resulting in highly fragmented, exceptionally short sequencing reads ¹⁸.

Reassessment of Brain and Placental Microbiomes

By applying a novel mathematical metric that normalizes microbial read length to host read length (the Median Length-Adjusted metric), researchers rigorously re-evaluated human tissues across the body ¹⁸¹⁹. The published results were definitive and highly reproducible. Biopsy sites with natural exposure to the external environment or mucosal connections - such as the gastrointestinal tract, the cervix, the vagina, and the skin - exhibited long microbial DNA fragments, confirming the undeniable presence of genuine, intact microbial communities ¹⁸.

Conversely, tissues historically considered sterile - including the brain, the deep pulmonary parenchyma, the kidneys, the blood, and the placenta - showed strictly short, highly fragmented microbial DNA profiles that were mathematically indistinguishable from negative laboratory controls ¹²¹⁸¹⁹.

This rigorous fragment-length analysis has led to a robust, international scientific consensus: the healthy human placenta and the human brain do not harbor resident microbiomes ¹²¹⁸¹⁹. The notion of the "placental microbiome," initially proposed in 2014, has been effectively and comprehensively refuted; the human womb remains a sterile environment, and earlier microbial detections were purely artifacts of laboratory contamination ^9122024. Similarly, the highly publicized "brain microbiome" has been entirely debunked as a sequencing artifact resulting from environmental contamination and host DNA misclassification ¹⁸¹⁹⁶². Any definitive, structurally intact microbial presence detected in the brain or placenta is highly indicative of a pathological infection, such as meningitis or chorioamnionitis, or a transient translocation of dead bacterial fragments, not a symbiotic, resident ecosystem ¹².