Bioindicators and Biomarkers


The health of an ecosystem can be examined through the use of bioindicators (BI), while the health of a human being can be determined using some molecules such as biomarkers (BM). BI are complete organisms or part of them that can be measured to detect changes in the environment, the presence of pollution and its effect on the ecosystem, as well as the observation of the progress of environmental clean-up. On the other hand, specific kinds of BI are the BM, which are biomolecules, secondary metabolites or measurable parameters used in medical research and practice to provide an insight into the mechanics and course of a disease. In general BM are classified into three groups: exposure, effects or susceptibility, and their role depends on the sensitivity, specificity, reliability and reproducibility of the methods used in the determination of the target molecule selected to be an specific BM, and it has to be validated under the development of guidelines, supported with good laboratory practice, epidemiological studies and clinical trials. BM can be used to detect subclinical stages, to become a diagnostic tool, to observe the efficacy of the treatment or monitoring the different stages on the development of the pathology.

Keywords: Bioindicator, Biomarker, Biomonitors, Ecological Health, Pathology prognosis.


The lifestyle, high pollution level produced by anthropogenic activities, and natural disasters have created the necessity to evaluate the ecological health of the environment, and also, to determine the effect on human health 1. The use of biological entities for that purpose allows establishing, through these indicators, diverse parameters such as the ecosystem state.

For example, the health state of a body of water can be easily determined by the characterization of its chemical and physical components, the abundance, distribution and diversity of the microbiota found inside it. If the body of water is damaged, there must be degradation and lost of the biodiversity; therefore, the presence or absence of the organisms allow measuring the environmental health 2.

Biomonitoring is generally defined as the use of a living organism that determines the conditions or environmental changes. Whilst the historical research has been focused on ecological methods such as organization levels from suborganims, populations, communities and ecosystems, the actual tendencies of biomonitoring are based on methods that allowobserving the impact of external factors inside the ecosystems, and the development of the changes in a period of time. The BI is a complete organism, part of it or a community of subjects that contains information about the quality of the environment 3.

An ideal BI must be 4, 5:

  1. Easily recognizable
  2. Cosmopolitan distributed in the environment.
  3. Low motility to be considered as a local indicator
  4. Well known ecological characteristics
  5. Numerical abundance
  6. Can be taken to a laboratory and manipulated inside it
  7. High sensibility to the effect of the stressor
  8. Easy way to standardize the quantifying method
  9. BI need the interaction in the long term with the environment
  10. The capacity to react to sudden changes in the environment.
  11. Sampling must be dependable, simple and with low cost.

Depending on the ecosystem to be studied, the selection of a biomonitor varies depending on its own adaptation to the necessities, for example, for aquatic environments periphyton, a complex mixture of algae, cyanobacteria, heterotrophic microorganisms and detritus found in the surface of the majority of aquatic ecosystems, constitute an important source of food for invertebrates, tadpoles and some fish.Periphyton is also able to absorb and remove pollutants from the body of water. Another example of BI are the microinvertebrates of the bentonite, this organisms establish a link between organic matters and nutrient source with higher trophic levels; they possess sedentary habits, long life and the ability to integrate the acute effects with a reversible response to the stressor3.

Bioindicators and biomonitors

To detect the level of pollution using biological material as an indicator of the status of the ecosystem results cheap, dependable and a simple alternative to the conventional sampling methods. BI are the most trustful tools for environmental biomonitoring5.

Plants act as simple diffusers that accumulate pollutants in a higher concentration than the present in the surroundings, since they can absorb minerals, integrate pollutants from wastewaters, heavy metals, pesticides, etc. Leaves from trees, grass, lichen and mold are used as BI where the leaf surface, root and the routes of the pollutant are not completely clear about the tissue the xenobiotic will be fixed6.

Plants varies according to their specie, heavy metal accumulation capacity, for example, Salvinianatans accumulates mercury while the Spirodelapolyrhiza does it with zinc, and as well as Seratophyllumdemersum accumulates other heavy metals such as copper, chrome, iron, manganese, cadmium and lead 5.

Plants can also be used for biomonitoring the atmospheric conditions and its variations, in particular the use of vascular plants that allow the taxonomic identification in an easy way, the knowledge of vegetal physiology and the possibility to determine the specific part of the plant for the analysis 7.

A database that contains as much elements for biomonitoring can provide as much information as possible for the identification of the pollutant sources in some ecosystems. For this effect, multivariable analysis methods are generally used to evaluate different components such as nutrients, pollutants and trace elements 8.

Another important biomonitor for determining the atmospheric effect of pollutants such as metals, dust, acid gas, besides the traditional measurement equipment, are the lichens, which are very sensitive for the trace element quantification, metals and cumulated pollutants used as active monitors, transplanted or passively in situ. Lichen can also accumulate heavy metals, since their cells can metabolize or eliminate these chemicals. Garty9 indicates that lichen can alter qualitatively and quantitatively the accumulation of air pollutants and metals even when they cannot be considered as bioremediators.

Lichen have high resistance to the accumulation of toxic substance without representing a damaging risk for them 10, besides they allow the monitoring of different geographic areas and climates 11, 12, 13.

Inside habited areas, other bioindicators that can be considered are the ornamental plants, such as Durantarepens, a perennial plant present in parks and gardens of urban areas of Sicily. It has been observed that when this plants are located in high polluted areas like heavy traffic highways or where the air dispersion is not that good, there are a higher presence of the pollutants in the leafs tissue that when they are compared with plants of the same kind inside less contaminated areas, being sensitive in particular for the determination of lead, barium and suspended particles produced by inside combustion engines14.

Biomarker definition

Particular BI are biological entities or BM that can be validated as clinical indicators of the development of some organic disorders, to establish its progression and the degree of severity, as well as the efficacy of a therapeutic intervention 15.

At first, the definition of BM, was used to name proteins of the plasma where their concentration could indicate normal or pathological stages in the organism; nevertheless, this definition was enlarged to any substance or measurable parameter present in the organism that can be used to characterize the function of an organ or system, changes in genetic or protein expression, for example, the body temperature indicates if the patient has fever; high blood pressure is a marker to establish the risk for brain or heart strokes, high levels of cholesterol indicates a risk factor for coronary and vascular diseases16.

Biomarkers classification

In general, BM are classified in two big groups 17: 1.-Exposition BM that is used for establishing the risk and prognosis. 2. Disease BM, including exploration, diagnostic, monitoring and progression.

Other classifications have been established in the literature due to the richness and complexity of this field, for example:

1. Antecedent biomarker

Indicates the incidence of a particular disease

2. Exploration biomarker

Is useful to determine the subclinical stage of the pathology

3. Diagnosis biomarker

It indicates the presence of the disease

4. Stage biomarker

Define the degree of the disease, concerning the severity

5. Prognosis biomarker

Allows seeing the course of the disease and the response to the medical treatment 18

Another classification of BM depends on the parameters to be measured, for example, imagine BM, molecular BM that can be obtained from biological tissue samples as plasma, serum, biopsy, etc. Other kinds of BM are the nucleic acids used to detect punctual mutations, polymorphic sequence, gene expression or genotoxic damage 17

According to the application in the clinical field, another classification includes 16, 19, 20

a) Diagnostic biomarker: the troponins are determined in acute myocardial infarct

b) Stage of disease biomarker: natriuretic peptide indicates congestive heart failure

c) Prognostic biomarker: tumor markers such as CA125 for ovarian cancer, BRCA1 and 2 for breast cancer and prostate specific antigens.

d) Monitoring clinical response biomarker: glycosylated hemoglobin for type 2 Diabetes mellitus

Based on genetic and molecular biology, the BM is classified in 3 kinds 16:

Type 0: natural history markers (prognosis)

Type 1: biological activity BM (response to the therapy)

Type 2: surrogate marker (one or several markers to evaluate the therapeutic efficacy)

Guidelines to select a biomarker

The advantages of BM are: that they can identify the exposition to a xenobiotic early in the first stages of a disease, allowing to establish the molecular mechanisms of the pathology, considering the variability and prediction risk; for example, instead of waiting for a population to be affected for the exposition to a genotoxic. A study for the determination of chromosomal aberrations is a previous indicator before the massive expression of the phenomena can be observed in an open population 17.

The Development of BM must include the clinical aspect, where these steps should be taken into consideration 16,21:

1. Preclinical research applied to biological material where the BM could be identified, such as, sample of blood, nucleated cells, urine, saliva or tissue. The markers to be searched, could be genes, proteins, enzymes and metabolites, comparing a healthy sample with one affected to establish the correlation between the biomarker and the phenomenon under research.

2. Validation of the assay method, regarding to its ability to identify a pathology or altered stage when it is compared with a golden standard.

3. Retrospective and predictive epidemiological studies.

4. Clinical prospective studies must search the relationship of the biomarker, the beginning and development of disease.

5. In random clinical studies for treatment, it is important to determine if the treatment modifies the application of a biomarker.

Before introducing a biomarker to the clinical practice, it is necessary to respond several questions 19:

a) Distribution of the biomarker among the population and variability depending of demographic characteristics, such as gender, age and racial group.

b) If the biomarker correlates the risk factors and other physiological mechanisms with the disease

c) The limits, sensibility and specificity

d) The inclusion of the biomarker should increase the value of the prognosis, when it is compared to the models in use.

Biomarkers for exposition and background

The external exposure to a xenobiotic in the environment of a human being can be measured determining the concentration of it. Survey, allow establishing the story of the exposition according to the perception of the subject, while the laboratory determinations can identify the toxic agent in the tissues and measure directly the individual level of exposition, besides, it allows elucidating the toxicokinetic. From the epidemiological point of view, both the survey and laboratory data can provide the correlation between the exposition to a toxic agent and the risk for health and other factors that can interfere with the accuracy of the BM22.

To determine the genetic susceptibility, the use of the biomarker must consider the variation in absorption, bioavailability, elimination, and genetic repair mechanisms of DNA, evaluating the individual risk. Since the organism acts like an integrator of the exposition, some physiological factors could modulate the intake of that entity. A group of individuals cannot be assimilated as a homogeneous set exposed to a xenobiotic, in standard and reproducible conditions like in biomodels, where this variables are usually under control 20.

Exposition BM must be easy to collect and analyzed, with ethical validation and specificity on the response to a xenobiotic. The change in the value should be determined subclinically and reversible, and at least, preventive measures could be adopted. BM can be selective or nonselective, considering the kind of toxic agent of its measurable metabolites, in biological fluids such as lead level in blood, while the nonselective are nonspecific but suggest changes in the organism, for example, thioesters in urine are used as BM of exposition to electrophilic agents, and therefore are a reflexion of the absorption of mutagenic and carcinogenic compounds 23.

Evolution of pathology biomarkers

The BM to allow the early diagnosis also must be able to recognize the stages of the disease, in subclinical and atypical sings, besides it should establish 17:

a) Identification of subjects in subclinical stage

b) Reduction of the heterogeneity of the pathology in clinical or epidemiological studies

c) Reflex of the natural course of the pathology, from the induction, latency, to detection.

d) The objective of the clinical trial.

An example of this kind of BM are the related to the cancer development, since its applications includes the identification of new targets for the therapeutic treatment and can measure the efficacy in clinical trials. Inside this kind of BM, oncogenes, germline inheritance, mutations and epigenetics use the DNA and RNA as target molecules 24.

For cardiac pathologies even when troponin is the most specific biomarker, myoglobin and cardiac kinanes CK (Creatine Kinase) and CK-MB can be used also to determine damage not only in heart but in other muscles25.


Even when BM possess a large number of advantages, the biggest concern is the variability, since this represents a modification of the results, interindividual variability can modify the way that two different persons can react to the same exposure, depending on the ability of each one to metabolize the xenobiotic. This is related to laboratory mistakes; nevertheless, the group variability allowsestablishing the error factor of a BM. In this category it has to be taken into consideration other variables, like the use of drugs that can modify the biomarker response. BM must be based on epidemiological studies, to set the impact of variables such as diet and lifestyle that can influence in biological measurements 17.


The reliability of the laboratory results are the keystone in the use of BM, since a mistake can disqualify it as an indicator if it is not the right one. Pilot studies must be first done to establish the reliability. Changes in laboratory staff, used methods, storage and transportation, should not be able to modify the results for a specific biomarker. To validate a BM, this must be taken into consideration:26,27

a) Validation must show the degree of the accuracy of the BM for the studied phenomena

b) The construct validation has to give relevance to other characteristics of the disease or treatment

c) The criteria of the validation must show in an extensive way if the biomarker is correlated with high specificity to the pathology and it is used to measure the sensibility, specificity and predictive power.

Laboratory results as evidence are important to achieve the validation in the use of BM in clinical studies. The bibliographic research and clinical trials are necessary to determine the accuracy and guidelines for the application of a particular biomarker, based on the assay capacity and its translation into the clinic practice 15.


BI used for ecological studies are a useful tool for biomonitoring health of the environment, selecting some organisms as sentinels of the state of the ecosystems and BM are applied for medical purpose; nevertheless, the validation of both should go along with the standard of experimental design, epidemiological or clinical trials, considering good laboratory procedures, pilot studies and the development of the guidelines; this should increase the accuracy, reliability, interpretability and feasibility of laboratory measurements. The research to develop a BM will be translated into practice, allowing evidence based on facts to promote its clinical application to detect, predict and observe the efficacy of the treatment or development of the pathology.


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[a] Faculty of Public Health; Medical School, UAEH.