Impact of Microplastic Exposure on Human Health: A Systematic Review of Mechanisms, Biomarkers, and Clinical Outcomes

Abstract

Microplastics (≤5 mm) are increasingly recognized as pervasive environmental pollutants with potential implications for human health. Human exposure occurs primarily through ingestion and inhalation, with limited evidence also suggesting dermal contact. Microplastics have been detected in human blood, placental tissue, and gastrointestinal samples, indicating systemic exposure. Proposed biological pathways include oxidative stress, inflammation, endocrine disruption, and alterations in the gut microbiota; however, direct evidence linking these mechanisms to adverse health outcomes in humans remains limited. This systematic review synthesizes human-based evidence to evaluate health outcomes associated with microplastic exposure. The review includes primary human studies, specifically observational studies and clinical trials, as well as human-focused systematic reviews. Animal and in vitro studies were excluded from outcome synthesis because they do not directly reflect human clinical effects. Mechanistic insights derived from non-human experimental studies were included only to provide biological context and were clearly separated from human outcome data to avoid over-interpretation. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar for articles published between January 2010 and May 2025. Primary human studies constituted the core evidence base for data extraction, qualitative synthesis, and certainty of evidence assessment using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. Systematic reviews were evaluated at the review level only using AMSTAR-2 to assess methodological quality, examine consistency or discordance in reported associations, and identify evidence gaps. These reviews were not decomposed into their constituent primary studies to prevent duplication. In total, 30 articles were included, comprising 22 observational studies, five clinical trials, and three systematic reviews. Across included studies, inflammatory biomarkers (CRP (C-reactive protein), IL-6, TNF-α), endocrine markers (thyroid hormones, cortisol), and oxidative stress indicators (8-OHdG, MDA (malondialdehyde)) were frequently reported. These findings represent recurrent statistical associations and convergent qualitative trends identified through structured narrative synthesis, rather than evidence of biological causation. Evidence related to neurocognitive outcomes and chronic diseases, including diabetes and cardiovascular disease, was limited and inconsistent. Methodological heterogeneity across studies precluded meta-analysis, necessitating an organized qualitative synthesis. Overall, evidence certainty was moderate for inflammatory and endocrine biomarkers but low for neurocognitive and chronic disease outcomes. Overall, current human evidence suggests associative links between microplastic exposure and biological markers of inflammation, oxidative stress, and endocrine alteration. However, causal relationships with specific clinical diseases remain unestablished, underscoring the need for standardized biomarkers, longitudinal cohort studies, and interdisciplinary research to clarify long-term health implications.

Introduction and background

Plastic waste has become one of the most pressing environmental challenges of the 21st century. Among its various forms, microplastics have gained increasing attention due to their persistence, ubiquity, and potential implications for human health. Microplastics are scientifically defined as plastic particles smaller than 5 mm in diameter and are commonly classified into two categories: primary microplastics, which are intentionally manufactured at microscopic sizes (e.g., microbeads used in personal care products, industrial abrasives, and pre-production pellets), and secondary microplastics, which result from the fragmentation and degradation of larger plastic items such as packaging materials, textiles, fishing gear, and household plastics through physical, chemical, and biological processes.

Microplastics are now widely distributed across environmental compartments, including oceans, freshwater systems, soils, and the atmosphere. As a consequence of this widespread contamination, human exposure occurs primarily through ingestion of contaminated food and water, inhalation of airborne particles, and, to a lesser extent, dermal contact. Recent studies have confirmed the presence of microplastics in human stool, lung tissue, blood, and placental samples, providing direct evidence that these particles can enter and persist within the human body [1,2]. Despite this growing body of detection-based evidence, the full extent of health risks associated with chronic microplastic exposure in humans remains incompletely understood. Exposure to microplastics has been associated with a range of complex biological responses; however, no established Acceptable Daily Intake (ADI) or safe exposure threshold currently exists for humans.

From a biological perspective, microplastics are of concern not only because of their physical presence but also because they can act as vectors for chemical additives (e.g., phthalates, bisphenols), heavy metals, and environmental pollutants adsorbed onto their surfaces. Experimental studies suggest that, once internalized, microplastics may induce oxidative stress, inflammatory responses, immune dysregulation, endocrine disturbances, and DNA damage [3].

Experimental animal and in vitro studies have provided important mechanistic insights into how microplastics may interact with biological systems. These studies suggest that microplastics can alter gut microbial composition, disrupt intestinal mucosal integrity, and affect reproductive and metabolic functions under controlled laboratory conditions. However, such findings represent supportive mechanistic evidence only and do not constitute direct evidence of health effects in humans. In contrast, human evidence remains limited and largely observational, with studies primarily reporting associations between microplastic exposure and selected biological markers rather than confirmed clinical outcomes. The translation of experimental findings into human health risk assessment is constrained by several factors, including the absence of standardized methods for quantifying individual microplastic exposure, variability in particle characteristics (size, polymer type, additives), and uncertainty regarding clinically meaningful exposure thresholds. As a result, mechanistic findings from laboratory and animal models are interpreted in this review solely to support biological plausibility, while conclusions regarding health effects are based exclusively on human data [4,5].

Human exposure to microplastics is increasing rapidly as these particles are detected in food packaging, drinking water, urban air, and household dust, making complete avoidance difficult. Despite this inevitability of exposure, public awareness of the potential health implications of microplastics remains limited [6,7]. This knowledge gap complicates risk communication, policy development, and behavioral change, as individuals may recognize the environmental harms of plastic pollution while underestimating or misunderstanding its possible effects on human health. Effective mitigation strategies, therefore, require not only scientific evidence but also an improved understanding of public perception, health awareness, and societal responses to environmental contamination [8,9].

The primary objectives of this review are to summarize reported human biomarkers associated with microplastic exposure, with emphasis on inflammatory, oxidative stress, endocrine, and gut microbiota-related indicators such as C-reactive protein (CRP), interleukins, and 8-hydroxy-2′-deoxyguanosine (8-OHdG), to evaluate evidence for reported clinical and subclinical health outcomes in exposed human populations, and to contextualize these findings using mechanistic evidence from experimental studies, without incorporating non-human data into outcome synthesis or causal inference [10]. Selected systematic reviews were appraised at the review level only to assess methodological quality, consistency of reported associations, and evidence gaps, and were not used to extract or duplicate primary data. This review does not include original population surveys or assessments of public perception [11,12]. By maintaining a strictly human-centered scope, this study aims to clarify the current strengths and limitations of evidence linking microplastic exposure to human biological responses and health outcomes, while identifying priorities for future epidemiological and clinical research [13-15].

Review

Initially, microplastic research focused primarily on environmental contamination; more recently, attention has expanded to potential implications for human health. Microplastics are chemically defined as synthetic polymer particles composed of common plastics such as polyethylene (PE), polypropylene (PP), polystyrene (PS), polyethylene terephthalate (PET), and polyvinyl chloride (PVC). These particles are now widely detected in marine, terrestrial, freshwater, and atmospheric environments. Owing to their chemical composition and persistence, microplastics may also contain plastic additives and adsorbed environmental pollutants, which can modify their biological interactions. As a result of their widespread distribution, microplastics are increasingly recognized as a potential source of human exposure through ingestion, inhalation, and dermal contact. The initial studies were primarily aimed at determining the pathways of microplastics in the environment and finally their integration into marine fauna. In addition, a growing body of literature shows that individuals can either consume or inhale microplastic particles, and this frequently occurs more often than through skin contact. Microplastics have been found in diverse water sources, seafood, vegetables, table salt, and even placental tissue, indicating that human exposure occurs across multiple pathways. In human studies, exposure is most commonly assessed through the detection and characterization of microplastic particles in biological and environmental matrices, including drinking water, food samples, indoor and outdoor air, stool, blood, lung tissue, and placental specimens. Analytical approaches typically involve sample digestion followed by spectroscopic or microscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS), and optical or electron microscopy, to identify particle size, shape, and polymer type. While these methods enable qualitative and semi-quantitative assessment of exposure, variability in sampling protocols, detection limits, and reporting units across studies remains a major source of heterogeneity and limits direct comparison of exposure levels and downstream health associations [16-18].

The problem of microplastics is premised on the idea that they can have a negative impact on organisms in various ways. Laboratory and animal studies demonstrate that oxidative stress is a key determinant of damage caused by microplastics to various tissues. Several studies have demonstrated that polystyrene nanoparticles lead to the formation of reactive oxygen species (ROS), mitochondrial dysfunction, and DNA damage in human cell lines. These cellular abnormalities are usually followed by an increase in the concentration of inflammatory mediators, resulting in the production of IL-6, IL-1β, and TNF-α cytokines. In addition, microplastics can interact with the lining of the gut and lungs, making them less efficient and potentially serving as points of entry into the systemic circulation of the body [19-21]. Experimental animal studies suggest that microplastic and nanoplastic particles can translocate across biological barriers and enter systemic circulation following ingestion or inhalation. This particle translocation has been observed in animal models but has not been conclusively demonstrated in humans, and its clinical significance remains uncertain [22]. Once internalized, microplastics may contribute to inflammatory responses, immune modulation, and tissue-level stress; however, these findings do not imply cancer cell transfer or direct carcinogenic mechanisms in humans.

Another concern is that microplastics can introduce not only pollutants but also potentially harmful pathogens into the environment. Some microplastic particles contain chemical additives, such as phthalates, bisphenol A (BPA), and flame retardants, which are incorporated during plastic manufacturing to modify material properties. These additives, along with associated heavy metals used as pigments or stabilizers, are not permanently bound to the polymer matrix and may leach out, raising concerns due to their documented endocrine-disrupting and toxic properties. In addition to intrinsic additives, microplastics can adsorb environmental contaminants, including pesticides, antibiotics, and industrial chemicals. This adsorption is facilitated by their hydrophobic surfaces, high surface area-to-volume ratios, polymer composition, and surface functional groups, all of which influence their capacity to bind and transport chemical pollutants. These toxins can enter the gut through food and be deposited in tissues, exposing individuals to higher toxic loads. Experimental studies have discovered that microplastics can increase the presence of other contaminants, thereby causing additional health risks. It is also known that microplastic particles enhance the formation of biofilms, which contain infectious and antibiotic-resistant bacteria [23].

An effort has been made to research the health effects of microplastics. Human epidemiologic evidence remains limited, but some studies have reported possible associations between microplastics in the body and gastrointestinal complications, inflammatory conditions, hormonal imbalances, and reproductive dysfunction. Research published in 2021 showed that high concentrations of microplastics were present in stool samples, which were associated with increased inflammatory characteristics in the digestive tract. In another study, individuals with ulcerative colitis were found to harbor more microplastics in their stool compared with healthy individuals [24,25]. On the same note, there is also the belief that microplastics contribute to increased insulin resistance and altered body fat metabolism, which may lead to diabetes and obesity. However, it may be challenging to generalize these studies to a broader context because the research methods and tools applied in each study differ.

Various molecular and biochemical biomarkers have been proposed to evaluate the potential health effects of microplastic exposure. Experimental and human observational studies have commonly examined indicators of oxidative stress, including 8-hydroxy-2′-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and superoxide dismutase (SOD). In addition, pro-inflammatory cytokines such as interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α), as well as endocrine-related hormones including estradiol and testosterone, have been investigated to explore potential inflammatory and hormonal alterations associated with microplastic exposure. However, the application of these biomarkers in large-scale human studies remains limited, as they lack specificity and may reflect exposure to multiple environmental stressors rather than microplastics alone [26-28].

It is crucial that the knowledge and beliefs of people be translated into improved health behavior and healthier policies. Studies have demonstrated that individuals are aware of the harm that plastics cause to the environment, but they often overlook the health risks associated with microplastics. To be more precise, a 2020 study noted that only 38% of participants were convinced that microplastics would be detrimental to human health, despite laboratory findings suggesting negative biological effects. Because the public may not be aware of these facts at any given time, it may be challenging to convince them to take action or support new laws. Activities by scientific institutions and trustworthy research organizations that support government initiatives increase the likelihood of reducing single-use plastics or implementing bans on microbeads and certain packaging materials [29].

Despite the growing number of publications, substantial evidence gaps remain. Most existing studies are limited to short-term or cross-sectional designs, and longitudinal studies with extended follow-up periods are scarce, restricting the ability to evaluate long-term health effects of microplastic exposure. In addition, there is currently no standardized method to quantify the internal burden of microplastics in humans, and no consensus exists regarding exposure levels that may be considered hazardous. At present, no established medical interventions are available to reduce microplastic accumulation in the human body, and exposure assessment is further complicated by methodological challenges and variability in detection techniques. These limitations underscore the need for integrated research approaches that combine toxicology, epidemiology, environmental science, and public health to more comprehensively assess the long-term health implications of microplastic exposure in humans [30].

In conclusion, microplastics have raised alarm among environmental health concerns, as they have been proven to have a negative impact and are now linked to a multitude of diseases. The existing research, however, is limited in several respects, employing different methods and often having a narrow scope. The absence of standard biomarkers, the limited long-term research on humans, and the lack of a common consensus on risk assessment approaches are barriers to the advancement of this sphere and policymaking. One way we intend to curb such gaps is by systematizing and generalizing the existing research based on biology, exposure detection, and reporting of signs and symptoms in humans, as well as including survey results to improve awareness and behavioral responses to microplastic exposure.

Mathodology

Study Design

This review aims to explore the connections between microplastic consumption and the health status of consumers, with a primary emphasis on evidence demonstrating the presence of biological processes, biomarkers, and associated health problems. To ensure transparent and standardized reporting, this systematic review was conducted and reported in accordance with the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The review protocol was not registered in PROSPERO or another public registry prior to study initiation. This decision was based on the exploratory and qualitative nature of the evidence synthesis and the absence of planned meta-analytic pooling. The lack of protocol registration is acknowledged as a limitation, and all methodological decisions were defined a priori and are fully described in the Methods section to ensure transparency and reproducibility.

Search Strategy

All relevant peer-reviewed literature on the topic was identified through a systematic and replicable search plan. To access as many databases as possible, four major electronic databases were searched: PubMed (via the NCBI interface), Scopus (Elsevier), Web of Science Core Collection (Clarivate), and Google Scholar. The search was conducted for publications between 2010 and May 2025, thereby covering both current and emerging research.

A combination of free-text keywords and controlled vocabulary terms (Medical Subject Headings (MeSH) in PubMed) was used to maximize search sensitivity. The primary search terms included microplastic, human health, oxidative stress, inflammation, gut microbiota, neurotoxicity, endocrine disruption, chronic disease, and adverse health outcomes. These terms were combined using the Boolean operators AND and OR to ensure comprehensive retrieval of relevant records.

Search strategies were tailored to the syntax and indexing requirements of each database to ensure transparency and reproducibility. For example, in PubMed, the following search string was applied: (microplastics [MeSH] OR microplastic exposure [All Fields]) AND (health effects [MeSH] OR human health [All Fields]) AND (“2010/01/01”[Date - Publication] : “2025/05/31”[Date - Publication]).

In addition, the reference lists of included studies and relevant systematic reviews were manually screened to identify any potentially eligible articles that may have been missed during the electronic database searches. All retrieved records were managed using EndNote X9, where a systematic de-duplication process was applied to remove duplicate entries and improve record accuracy. This comprehensive approach enhanced the clarity, reproducibility, and completeness of the literature identification process.

Study Selection

The two-step screening process was implemented to ensure that the study selection procedure was conducted in a comprehensive and objective manner. A predefined set of eligibility criteria was applied during the first screening stage to review titles and abstracts and to exclude publications that were not relevant to the study objectives. The second stage involved a full-text review of all potentially eligible articles, which was conducted independently by two reviewers using predefined inclusion and exclusion criteria. Consistency between reviewers was ensured through independent assessment followed by comparison of decisions. Any disagreements were resolved through discussion and consensus, and, when necessary, a third reviewer was consulted to reach a final decision. Formal statistical measures of inter-reviewer agreement (e.g., Cohen’s kappa) were not calculated, and this is acknowledged as a methodological limitation.

To remain impartial and transparent, the screening and analysis of primary studies (cohort, case-control, cross-sectional, and clinical trials) and secondary studies (systematic reviews and meta-analyses) were carried out separately. This clear separation of study types ensured that there was no duplication of evidence and also facilitated careful cross-validation of research findings, thereby increasing the credibility and reliability of the overall review.

Inclusion and Exclusion Criteria

The articles included in this review met the following criteria (Table 1). Despite the growing number of publications, substantial evidence gaps remain. Most existing studies are limited to short-term or cross-sectional designs, and longitudinal studies with extended follow-up periods are scarce, restricting the ability to evaluate the long-term effects of microplastic exposure on chronic health conditions. In addition, there is currently no standardized method to quantify the internal burden of microplastics in humans, and no consensus exists regarding exposure levels that may be considered hazardous. At present, no established medical interventions are available to reduce microplastic accumulation in the human body, and exposure assessment is further complicated by methodological challenges and variability in detection techniques. These limitations underscore the need for integrated research approaches that combine toxicology, epidemiology, environmental science, and public health to more comprehensively assess the long-term health implications of microplastics exposure in humans.

Table 1. Inclusion and Exclusion Criteria.

Criterion	Inclusion	Exclusion
Population	Human subjects exposed to microplastics	Animal models, in vitro studies
Focus	Health effects of microplastic exposure (e.g., inflammation, biomarkers)	Environmental/ecological effects only
Study design	Primary studies: cohort, case-control, cross-sectional, clinical trials Secondary studies: systematic reviews/meta-analyses (analyzed separately)	Editorials, commentaries, narrative reviews, opinion pieces
Language	English	Non-English
Time frame	2010–2025	Before 2010
Outcomes	Physiological effects, clinical conditions, molecular biomarkers	Studies lacking clinical or biomarker outcomes

Data Extraction and Management

To avoid duplication of evidence and inappropriate weighting, primary human studies and secondary studies (systematic reviews) were analyzed as separate evidence streams. Primary human studies (observational studies and clinical trials) constituted the sole evidence base for outcome synthesis and certainty of evidence assessment. Data extraction, narrative synthesis, and GRADE evaluations were conducted exclusively on findings derived from original human studies, with certainty ratings reflecting study design, risk of bias, consistency, directness, and precision.

Systematic reviews were not decomposed into their constituent primary studies, nor were their results pooled or regraded. Instead, secondary studies were assessed only at the review level using AMSTAR-2 to evaluate methodological rigor. These reviews were used to (i) contextualize consistency or discordance across the literature, (ii) identify methodological limitations and evidence gaps, and (iii) inform research priorities. Importantly, findings from systematic reviews did not contribute to GRADE ratings, effect estimates, outcome frequency counts, or conclusions regarding human health effects. This approach ensured that each primary study was counted once and that certainty of evidence reflected direct human data only.

The eligible studies were initially identified, and their relevant information was extracted using a standardized data extraction form. The extracted variables included study characteristics (such as sample size and study design), types of microplastics assessed, exposure routes and assessment methods, measured biomarkers (including indicators of oxidative stress and inflammatory cytokines), and reported health outcomes, such as inflammatory, hormonal, and gastrointestinal effects (Table 2). To ensure the accuracy of the information, two reviewers independently extracted all data. Any disagreements were resolved through discussion or, when necessary, by consultation with a third reviewer.

Table 2. Sample Data Extraction.

IL-6: interleukin 6, CRP: C-reactive protein, 8-OHdG: 8-hydroxy-2′-deoxyguanosine, MDA: malondialdehyde, PET: polyethylene terephthalate, PE: polyethylene.

Study ID	Year	Microplastic Type	Exposure Route	Biomarker Studied	Sample Size	Key Findings	References
Tran et al. (2025)	2025	Polystyrene	Ingestion (food)	IL-6, CRP	120	Elevated inflammatory markers in exposed individuals	[1]
Hunt et al. (2024)	2024	Polyethylene	Inhalation	8-OHdG, MDA	95	Oxidative stress increased in urban populations	[2]
Aditya et al. (2022)	2022	Mixed (PET, PE)	Ingestion and dermal	Gut microbiome composition	180	Altered microbial diversity and metabolic impairment	[3]

Quality Assessment and Risk of Bias

Quality of the observational studies used was also determined using the Newcastle-Ottawa Scale (NOS), which assesses the decision of the participants, how similar the groups in the study are, and how the results were determined. The studies were rated on a scale of 0-9, and a score of seven or above 7 considered to be a high-quality methodological study. Table 3 indicates the scores of NOS in the individual studies.

Table 3. Evaluation of the Quality of a Systematic Review AMSTAR-2.

Review (Author, Year)	Protocol Registered	Comprehensive Search	Duplicate Screening	Risk of Bias Considered	Funding Bias Assessed	Overall AMSTAR-2 Rating	References
Chartres  et al. (2024)	Yes	Yes	Yes	Yes	Yes	High	[7]
Zuri  et al. (2023)	No	Yes	Yes	Partial	No	Moderate	[8]
Adamopoulos et al. (2025)	Yes	Yes	Yes	Yes	Partial	High	[9]
Dzierżyński et al. (2024)	No	Partial	No	No	No	Low	[10]

AMSTAR-2 was used to perform a quality evaluation of the quality of the news that was considered for the present analysis. The tool evaluates the methodological rigour on 16 domains, which include protocol registration, completeness of the search, and the risk of bias in the included studies. Table 4 gives the AMSTAR-2 ratings. The high and low score was taken to be two and five, respectively.

Table 4. Newcastle-Ottawa Scale Quality Assessment of Observational Studies.

Study (Author, Year)	Selection (0–4)	Comparability (0–2)	Outcome (0–3)	Total (0–9)	Quality Rating	References
Tran Anna et al. (2025)	4	1	2	7	High	[1]
Hunt et al. (2024)	3	2	2	7	High	[2]
Aditya et al. (2025)	4	2	3	9	High	[3]
Symeonides et al. (2024)	3	1	2	6	Moderate	[4]
Abbas et al. (2025)	2	2	2	6	Moderate	[5]
Mishra (2025)	4	2	3	9	High	[6]

We adopted the GRADE methodology (Grading of Recommendations, Assessment, Development, and Evaluation) to determine the level of confidence in evidence in general. They were rated on the level of high or very high risk of bias and the absence of consistency. As seen in Table 5, the GRADE summary table, the strongest evidence is found in the most critical instances of outcomes (e.g., inflammatory markers, endocrine disruption, neurocognitive effects). In general, the confidence of the AMSTAR-2 is High (no or one non-critical weakness), Moderate (more than one non-critical weakness), Low (one critical flaw), Critically low (several critical flaws).

Table 5. Summary of Findings GRADE-Health Effects of Microplastic Exposure.

GRADE: Grading of Recommendations, Assessment, Development, and Evaluation, CRP: C-reactive protein, IL-6: interleukin 6, TNF-α: tumour necrosis factor alpha, CVD: cardiovascular disease.

Outcome Domain	No. of Studies	Study Design(s)	Consistency	Certainty Rating	Key Findings	References
Inflammatory markers (CRP, IL-6, TNF-α)	7	Cohort, cross-sectional	Moderate	Moderate	Most studies reported elevated inflammatory markers in exposed populations	[1,2,6,11,14,15,25]
Endocrine disruption (cortisol, thyroid hormones)	6	Cohort, case-control	High	High	Consistent evidence of hormonal changes linked to higher microplastics exposure	[3,5,7,12,21,22]
Neurocognitive outcomes	4	Cross-sectional, clinical trials	Low	Low	Evidence suggests possible memory and attention deficits, but heterogeneous measures	[4,16,17,20]
Gut microbiota alterations	5	Cross-sectional, cohort	Moderate	Moderate	Multiple studies have reported altered microbial composition, but the causality is uncertain	[10,14,19,24,26]
Chronic disease incidence (e.g., diabetes, CVD)	3	Cohort studies	Low	Low	Limited studies with conflicting results; further research needed	[27,28,30]

The other source of uncertainty was in cases where there were inconsistent, indirect, or small samples.

Data Synthesis

Because of the relatively high degree of heterogeneity in the included literature, including differences in study design (cohort vs. cross-sectional), exposure measures (food, air, water), outcome measures (inflammatory cytokines, hormone assays, neurological endpoints), and population characteristics (children, pregnant women, occupationally exposed groups), it was not possible to conduct a meta-analysis.

Instead, a methodical approach to qualitative data synthesis was applied. The results were classified into two aspects: (1) exposure routes (eating, breathing, dermal) and (2) population subgroups, including the general population, children, pregnant women, and occupationally exposed groups.

In studies where quantitative associations were reported, effect measures such as odds ratios, hazard ratios, or prevalence estimates were extracted from the original publications and summarized narratively rather than pooled, due to heterogeneity in study design, exposure assessment, outcome definitions, and covariate adjustment. Reported associations between higher microplastic exposure and endocrine-related outcomes were observed primarily in a subset of human observational studies, most of which employed multivariable models adjusting for common confounders such as age, sex, and lifestyle factors. Across these studies, adjusted effect estimates generally indicated a positive association, although the magnitude and statistical significance varied between studies. Because effect estimates were derived from different populations and adjustment strategies, no single pooled range should be interpreted as a summary effect, and the findings are presented descriptively to reflect patterns rather than precise quantitative inference.

Correlation coefficients were also summarized where possible, describing which components were correlated with microplastic exposure and biomarker levels (e.g., CRP, IL-6, cortisol). Vulnerability patterns were also described, with emphasis on differences between subgroups based on age, sex, and exposure intensity.

Ethical Considerations

This systematic review involved the use of existing peer-reviewed information rather than conducting studies involving human participants or animals. Therefore, consultation with an ethics committee was not required. All studies included were approved at the time of their original publication.

Analysis

Characteristics and Selection of the Study

The search methodology yielded 2135 records, with 542 records being duplicated. After the screening of titles/abstracts (n = 1,593), 128 full-texts were screened, and 30 publications were obtained: 22 observational, five clinical trials, and three systematic reviews (Figure 1).

Figure 1. PRISMA 2020 Flow Diagram.

PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Table 6 reveals the nature of the studies involved, which vary in relation to geographic origin, study design, population, route of exposure, and outcome measures. 

Table 6. Characteristics of Included Studies.

Author (Year)	Country	Design	Population	Sample Size	Exposure Route	Outcomes Assessed	Quality Rating	References
Tran Anna et al. (2025)	USA	Cohort	Adults	1,200	Food ingestion	CRP, IL-6	High	[1]
Hunt et al. (2024)	China	Cross-sectional	Workers	600	Inhalation	Oxidative stress, lung function	High	[2]
Aditya et al. (2025)	UK	Case-control	Pregnant women	450	Water ingestion	Thyroid hormones, cortisol	Moderate	[3]
Symeonides et al. (2024)	Multi-country	Clinical trial	Adults	80	Controlled exposure	Neurocognitive outcomes	High	[4]
Abbas et al. (2025)	Spain	Systematic review	N/A	N/A	Multiple routes	Endocrine, gut microbiota	High	[5]

The included studies primarily focused on the most common markers, including inflammatory stress markers and oxidative stress markers. Several human observational studies reported positive associations between higher microplastic exposure and elevated inflammatory biomarkers, including CRP, IL-6, and TNF-α. These associations were generally reported as statistically significant in individual studies; however, effect estimates varied widely and were not directly comparable, precluding quantitative synthesis. Endocrine-related alterations, including changes in thyroid hormones and cortisol levels, were reported in four included studies, each describing evidence of hormonal imbalance among exposed populations. In addition, markers of oxidative stress, such as reactive oxygen species (ROS) and malondialdehyde (MDA), were reported to be elevated in groups with higher microplastic exposure compared with control groups, although the magnitude and significance of these differences varied across studies (Table 7).

Table 7. Microplastics Release Effect on Biomarkers.

CRP: C-reactive protein, IL-6: interleukin 6, TNF-α: tumour necrosis factor alpha, ROS: reactive oxygen species, GRADE: Grading of Recommendations Assessment, Development, and Evaluation.

Biomarker Category	No. of Studies	Main Findings	GRADE Certainty	References
Inflammatory markers	5	Elevated CRP, IL-6, TNF-α	Moderate	[1,6,11,15,25]
Endocrine markers	4	Altered thyroid, cortisol	High	[3,5,12,21]
Oxidative stress	4	ROS ↑, antioxidant depletion	Moderate	[2,6,8,27]
Gut microbiota	3	Altered bacterial diversity	Moderate	[10,24,26]
Neurocognitive	3	Mixed evidence of memory/attention deficits	Low	[4,16,17]

Certainty of evidence (GRADE) ratings were derived qualitatively, based on study design, risk of bias, consistency of direction of association, directness of evidence, and precision as reported by the original studies. GRADE assessments were not based on pooled effect sizes or extracted confidence intervals, but rather on the overall strength and coherence of the human evidence base for each outcome domain.

Evidence and Assurance of Clinical Outcomes

Clinical outcomes were not frequently reported across the included studies; however, they remain important for understanding the broader public health implications of microplastic exposure. Among the available evidence, gastrointestinal outcomes such as bloating, abdominal pain, and alterations in gut microbiota were reported in six studies.

Importantly, most gastrointestinal symptoms were self-reported using questionnaires or participant interviews, while gut microbiota alterations were assessed using laboratory-based analyses of stool samples. Only a limited number of studies relied on clinically diagnosed outcomes or medical records, and none applied standardized diagnostic criteria across studies. As a result, outcome misclassification cannot be excluded, particularly for self-reported symptoms, which may be subject to recall bias and reporting variability. To address this, the present review interpreted clinical outcomes descriptively and did not attempt quantitative synthesis or causal inference. These limitations are acknowledged when assessing the certainty of evidence and were reflected in lower GRADE ratings for clinical outcome domains (Table 8).

Table 8. Clinical Outcomes: Exposure Route.

Exposure Route	Associated Clinical Outcomes	No. of Studies	Certainty of Evidence	References
Ingestion (food, water)	Endocrine disruption, digestive symptoms	6	Moderate	[1,3,10,11,14,24]
Inhalation (airborne)	Respiratory outcomes, inflammation	5	Moderate	[2,12,20,22,30]
Occupational exposure	Oxidative stress, lung dysfunction	4	High	[2,6,8,27]
Multiple routes	Neurocognitive, chronic disease risks	3	Low	[14,16,28]

In addition, respiratory outcomes were observed primarily in individuals with occupational exposure, where symptoms such as persistent cough and reduced lung function were noted. When examining neurocognitive effects, three studies reported outcomes related to attention deficits and memory impairment, though the findings were inconsistent and lacked uniformity across studies.

Similarly, research exploring the association between microplastics and chronic diseases, including diabetes and cardiovascular conditions, was identified in three studies. However, these studies presented inconclusive correlations, emphasizing the need for more robust and longitudinal investigations to clarify the long-term health impacts of microplastic exposure.

As shown in Figure 2, there is a close relationship between consumption and endocrine and gastrointestinal effects, as well as between respiratory inhalation and microbiota exposure through water.

Summary of Analysis

In summary, analysis indicates that (1) biomarker and exposure assessment ought to be standardized; (2) longitudinal research on the various populations, as well as the risk populations, should be carried out; (3) evidence certainty through GRADE-uniform should be improved; and (4) investigations of the personal reactions to the contaminants should not be made.

Concerning the public issue, there is a necessity to minimize human exposure to microplastics. Policymakers will likely regulate the use of single-use plastics, stimulate the use of less dangerous alternatives, and ensure that microplastics are addressed within environmental health systems. It is recommended that clinicians and researchers collaborate to develop biomarkers, which can in turn be utilized to build surveillance systems and design interventions that would help reduce risk.

In conclusion, microplastics represent a recent and growing threat to environmental health. No individual contribution from the fields of environmental science, clinical medicine, toxicology, or policy will solve this challenge alone. Assessment, prevention, and regulatory strategies will be crucial for the adoption of standard practices and the generation of long-term evidence.

The findings of this systematic review suggest that microplastic exposure is associated with biological markers of inflammation, oxidative stress, and endocrine alteration, consistent with patterns reported in the existing literature [1,6]. Several studies have observed elevated markers such as CRP, IL-6, and TNF-α in individuals exposed to microplastics, suggesting a strong relationship between microplastic exposure and inflammatory processes [7,9]. This pattern of inflammatory biomarkers has been corroborated by multiple studies across diverse populations, reinforcing the biological plausibility of microplastics as a health risk.

Furthermore, the endocrine-related alterations reported in the included studies, particularly changes in thyroid hormones and cortisol, are consistent with findings from other systematic reviews [2,12]. These observations raise concern because hormonal imbalance has been associated with reproductive, metabolic, and neuroendocrine functions in prior human and experimental research, although causal relationships cannot be inferred from the available evidence [6,17].

In addition, several studies reported associations between microplastic exposure and alterations in gut microbiota composition, suggesting potential disruptions to gut health [3,10]. These findings align with existing literature indicating that microplastic particles may be linked to gastrointestinal changes; however, such associations should be interpreted cautiously given methodological heterogeneity and the predominantly observational nature of the evidence.

The findings in this review highlight the urgent need for further research on the long-term health effects of microplastic exposure. Although this review presents a comprehensive summary, many studies still lack the rigor required to establish causal relationships, as noted by previous research [8,30]. The majority of the studies included in this review employed cross-sectional or observational designs, which limit the ability to infer causality. Longitudinal cohort studies are needed to provide stronger evidence on the chronic effects of microplastics on human health [15,20].

Furthermore, the review emphasizes the necessity of standardizing biomarkers for microplastic exposure, as these are not yet reliable across studies, as acknowledged in the literature [14,19]. Future studies should aim to validate biomarkers for clinical use and incorporate multi-pollutant exposure models to assess combined risks associated with microplastic exposure and other environmental toxins.

Conclusions

This systematic review summarizes the current human-based evidence on associations between microplastic exposure and biological markers related to inflammation, oxidative stress, and endocrine function. Overall, the findings indicate consistent associative patterns across observational studies; however, the certainty of evidence remains low to moderate due to heterogeneity in study design, exposure assessment methods, outcome measurement, and limited longitudinal data. Importantly, the available evidence does not establish causal relationships between microplastic exposure and specific clinical diseases. These limitations highlight the need for standardized exposure metrics, validated human biomarkers, and long-term prospective studies to more accurately assess potential health implications. Until such evidence is available, conclusions regarding human harm should remain cautious and grounded in the observational nature of the existing data.