Review

The Antimicrobial Effects of Coffee and By-Products and Their

Potential Applications in Healthcare and Agricultural Sectors:
A State-of-Art Review
Rosa Castro-Díaz 1 , Norma Patricia Silva-Beltrán 2 , Nohemi Gámez-Meza 1, * and Kadiya Calderón 1, *

1 Departamento de Investigaciones Científicas y Tecnológicas, Universidad de Sonora,

Hermosillo C.P. 83000, Sonora, Mexico; [email protected]
2 Department of Environmental Science, Water Energy Sustainable Technology (WEST) Center,
University of Arizona, Tucson, AZ 85745, USA; [email protected]
* Correspondence: [email protected] (N.G.-M.); [email protected] (K.C.)

Abstract: Coffee is one of the most consumed beverages around the world. Its produc-
tion is dominated by the species Coffea arabica and Coffea canephora. However, the coffee
elaboration process leads to generating a significant amount of waste, which arises in
various stages of coffee bean processing and is rich in natural bioactive compounds such as
phenolic compounds and alkaloids. Particularly, chlorogenic and caffeic acids have a high
antimicrobial potential and have been demonstrated to be effective against bacteria and
viruses of healthcare and food relevance, including multi-resistant pathogens. However,
the production and accumulation of coffee waste have a negative environmental impact
since they can contaminate the surrounding environment due to the presence of organic
molecules such as caffeine and tannins. In this context, exploiting natural resources as
a source of compounds with the antimicrobial potential of, for example, the bioactive
compounds obtained from coffee, has been evaluated in previous works. This review
aims to summarize the current knowledge on the antimicrobial properties of coffee and its
by-products and their potential application in the healthcare sector and disease control in
agricultural crops, with particular emphasis on improving sustainability and efficiency in
Academic Editor: Alejandro
Rodriguez-Sanchez
agriculture through making use of waste, which carries high importance in today’s society.

Received: 27 November 2024

Keywords: Coffea arabica; Coffea canephora; coffee by-products; antimicrobial activity;
Revised: 17 December 2024
Accepted: 17 December 2024
sustainable agriculture
Published: 21 January 2025

Citation: Castro-Díaz, R.; Silva-

Beltrán, N.P.; Gámez-Meza, N.;
Calderón, K. The Antimicrobial Effects 1. Introduction
of Coffee and By-Products and Their Currently, coffee is one of the most consumed beverages, leading the global market
Potential Applications in Healthcare
with an estimated production, in the year 2021, of 168.6 million 60 kg bags, with a global
and Agricultural Sectors: A State-of-
consumption of up to 175.5 million bags. Coffee has also been used for medicinal purposes
Art Review. Microorganisms 2025, 13,
215. https://doi.org/10.3390/
and added to a wide variety of cosmetic products. In the agricultural sector, coffee has
microorganisms13020215 been used as an organic fertilizer due to its nutrient content [1–3]. The main producers are
Latin American countries such as Colombia and Brazil, Asian countries such as Indonesia
Copyright: © 2025 by the authors.
Licensee MDPI, Basel, Switzerland.
and Vietnam, and African countries such as Ethiopia. However, Europe is considered
This article is an open access article the continent with the highest level of coffee beverage consumption, estimated at a third
distributed under the terms and of the total global consumption of this product [2]. Coffee production is dominated by
conditions of the Creative Commons two species: Coffea arabica, which constitutes 58% of the world’s production, and Coffea
Attribution (CC BY) license
canephora, colloquially known as Robusta coffee, which represents 42% of the estimated
(https://creativecommons.org/
values for the years 2020–2021 [3].
licenses/by/4.0/).

Microorganisms 2025, 13, 215 https://doi.org/10.3390/microorganisms13020215

Microorganisms 2025, 13, 215 2 of 20

The coffee elaboration process leads to the generation of a significant amount of waste,
which arises in various stages of coffee bean processing. Initially, coffee beans represent
50% of the total weight of the fruit, while the remaining 50% consists of the husk, pulp,
mucilage, and parchment. These by-products are the residues obtained during the primary
processing of green beans. Once these beans undergo the roasting process, another waste
known as silver skin is removed, which is a layer directly covering the coffee beans. Finally,
during the preparation of coffee beverages, commercially in coffee shops or at home, a last
residue called spent coffee grounds or coffee waste is produced [4].
The production and accumulation of spent coffee grounds have a negative environ-
mental impact since they can contaminate the surrounding environment due to the presence
of organic molecules such as caffeine and tannins. This is relevant since approximately
2 billion tons of this product is produced per year [2].
Within the broad spectrum of molecules found in spent coffee grounds, natural bioac-
tive compounds such as phenolic compounds and alkaloids stand out. Additionally, during
the coffee roasting process, certain molecules called melanoidins are formed, contributing
to the coffee’s flavor. Collectively, these compounds confer to coffee antioxidant, neurostim-
ulant, anti-inflammatory, and antimicrobial properties, among others. These properties are
also present in this by-product obtained from coffee drink, since a significant amount of
phytochemicals are retained within it [5].
One of the most important current challenges facing the healthcare sector is the
development of antibiotic resistance by many bacteria, which limits the efficiency of the
medications used daily for the treatment of a wide range of diseases. Antibiotic resistance
also spreads in the agricultural sector, as the medications used to control diseases in
crops are often the same as those used in humans [6]. This situation provokes the need
to explore and exploit natural resources as a source of compounds with antimicrobial
activity [7]. Research has shown that bioactive compounds extracted from coffee possess
antimicrobial properties, demonstrating efficacy against various Gram-positive and Gram-
negative pathogens of healthcare and nutritional relevance [8,9]. Additionally, the recent
pandemic caused by the SARS-CoV-2 virus has increased the need to identify natural-origin
compounds with antiviral activity. In this sense, studies have also been conducted on
the potential of coffee against viruses such as influenza, herpes, and COVID-19, showing
promising results [10–12].
This review examines the antimicrobial properties of coffee and their potential appli-
cations in the health sector and disease control in agricultural crops. It highlights the latest
research findings, with a particular emphasis on the innovative use of spent coffee grounds.
Key topics include the composition of coffee, its antimicrobial properties, and the potential
of spent coffee grounds as a valuable resource.

2. Classification of Active Compounds in Coffee and Their

Biological Effect
The coffee-producing plants belong to the Coffea genus of the Rubiaceae family. They
are evergreen shrubs that typically reach an average height of 3 to 3.5 m, producing white
flowers and the fruit known as cherry, which contains two seeds inside corresponding to
the green coffee beans. This group comprises an estimated 103 species distributed across
the continents of America, Africa, and Asia. Despite the high number of species, only
two of them are currently cultivated for commercial purposes: Coffea arabica and Coffea
canephora [13].
Despite coffee being consumed mainly for its flavor and neurostimulant activity, it
presents properties that positively affect human health. These properties are conferred by
the bioactive compounds, which come directly from the secondary metabolism of the plant
Microorganisms 2025, 13, 215 3 of 20

of origin. Some of these molecules correspond to phenolic compounds, which originally

played a protective role against diseases in the plant [14]. Phenolic compounds are char-
acterized by the presence of a hydroxyl group attached to an aromatic ring, known as a
phenol. These are further divided into simple phenolic compounds, which are character-
ized by having the simplest structure consisting of a single phenol group, and polyphenols,
which are formed by more than one phenol unit [15].

2.1. Phenolic Acids

In coffee, the predominant phenolic compounds belong to the first group, mainly con-
sisting of hydroxybenzoic acids and hydroxycinnamic acids. Among the hydroxybenzoic
acids in coffee, compounds such as gallic acid and syringic acid are present (Figure S1) [16].
These types of compounds are characterized by the presence of a carboxyl functional group
attached to the benzoic (aromatic) ring [15]. Chlorogenic, caffeic, ferulic, and p-coumaric acids
are hydroxycinnamic acids that can be found in coffee [16,17]. This group is characterized
by the presence of a carboxyl group, which is connected to the phenol group by a carbon–
carbon double bond (C=C) [15]. The antimicrobial activity of coffee is predominately due to
chlorogenic acids, which are the most relevant compounds. Chlorogenic acids are formed
through the esterification of caffeic acid and quinic acid, with over 300 different types found in
coffee [7,18]. Green coffee beans rank second in chlorogenic acid content, after yerba mate
(Ilex paraguariensis). However, coffee is the main contributor to chlorogenic acid intake in
the diet, with around 200 mg contained in 200 mL, equivalent to the content of an average
cup of coffee, and being more abundant in C. canephora, reaching values of up to 8 g per
100 g of dry matter. The antimicrobial activities are attributed to chlorogenic acids [18,19].
In general, the total content of chlorogenic acids present in coffee is determined by the
degree of ripeness of the green beans, the variety of coffee, and the geographic location of
the cultivation origin [17]. Another important hydroxycinnamic acid due to its biological
activity present in coffee is caffeic acid (Figure S2b). It is typically found as a simple ester
with quinic acid or a saccharide. Like chlorogenic acids, caffeic acid has also been shown to
have antimicrobial activity [20].
Within the group of polyphenols, coffee contains molecules such as flavonoids, specifi-
cally compounds like catechin, epicatechin, and quercetin (Figure S3) [21]. The antioxidant
activity of coffee, characterized by its ability to neutralize free radicals in the body, is
primarily attributed to these compounds. To a lesser extent, they also contribute to the
antimicrobial activity of coffee and its derivatives [22,23]. Notably, catechin obtained from
green tea has demonstrated a growth-inhibiting effect against pathogens such as Streptococ-
cus mutans [24]. The antibacterial activity of quercetin obtained from various plant products
against both Gram-negative and Gram-positive bacteria has also been reported, including
an inhibitory effect on biofilm formation in pathogenic microorganisms [25].

2.2. Alkaloids
Another group of bioactive compounds represented in coffee are alkaloids, which are
nitrogenous organic compounds with a heterocyclic structure [26]. The most well-known
alkaloid in coffee is caffeine (Figure S4a), which is popular for being a central nervous
system stimulant, making it one of its main attractions for the average consumer [1].
Caffeine is a purine-type alkaloid and is one of the compounds that gives bitterness to
coffee. Like with chlorogenic acids, caffeine content in C. canephora beans is higher than in
C. arabica, with approximately twice the concentration. However, the amount of caffeine
present in coffee brews depends on factors such as the cultivation origin, the type of bean,
and the method of beverage preparation [17]. Trigonelline (Figure S4b) is the second
most abundant alkaloid in green coffee beans. It is a derivative of pyridine and is formed
Microorganisms 2025, 13, 215 4 of 20

through enzymatic methylation of nicotinic acid. Like caffeine, it contributes to the flavor
and aroma of coffee. Trigonelline has been found in greater quantities in Arabica coffee than
in Robusta coffee; however, its concentration depends on factors such as coffee variety and
environmental conditions in the cultivation region [1,17]. Various studies have attributed
part of the antimicrobial activity found in coffee to these compounds. In the case of caffeine,
it has been observed that when acting alongside a clinically used antibiotic, it can enhance
its bactericidal activity against certain microorganisms [7,27,28].
During the roasting process of green coffee beans, many of the natural components of
the plant are transformed, giving rise to new ones. Melanoidins are one of the compounds
formed during this process, which are nitrogenous molecules of high molecular weight
with a brown color, formed by a particular mechanism known as the Maillard reaction [29].
This reaction occurs during the processing of certain products at high temperatures and
involves the reaction between a free amino group and the carbonyl group of a reducing
carbohydrate [30]. Melanoidins are primarily composed of carbohydrates such as ara-
binogalactans and galactomannans, phenolic compounds, and proteins [29,31]. It has
been demonstrated that coffee melanoidins exert significant antimicrobial effects against
clinically and nutritionally relevant pathogens [32].

2.3. Terpens
In coffee, other bioactive compounds such as terpenes can also be found. Terpenes
are characterized as monomers derived from another compound known as isoprene and
are natural secondary metabolites of a wide variety of plants. They can be found in
microorganisms, such as bacteria, fungi, and algae. These molecules are classified according
to the number of isoprene rings present in their structure, resulting in compounds such as
monoterpenes, diterpenes, and triterpenes [33].
Among the terpenes that can be found in coffee, diterpenes stand out. They are defined
as pentacyclic alcohols formed by the union of four isoprene units on a 20-carbon skeleton.
The most abundant diterpenes in coffee are kahweol and cafestol (Figure S5), with C. arabica
presenting the highest content of both compounds [17]. An unfiltered cup of coffee usually
contains 3 to 6 mg of these compounds [34]. Diterpenes are particularly attributed with
antioxidant activity, as they exert a protective effect against damage caused by oxidative
stress promoted by factors such as DNA itself and hydrogen peroxide. It has also been
found that these molecules have an anti-inflammatory effect [17]. In plants, diterpenes
have shown antifungal effects against phytopathogens such as Colletotrichum gloeosporioides
and Fusarium oxysporum, with cafestol being particularly effective. This is one of their
main activities as natural secondary metabolites, playing a protective role against fungal
pests [35].

3. Chemical Composition of Coffee Extracts and By-Products

The bioactive compounds present in coffee have garnered the interest of many re-
searchers primarily due to their potential biological activity and possible application in
sectors such as the pharmaceutical, food, and agricultural industries, etc. To study these
compounds, coffee or products derived from its production need to undergo an extraction
process that allows for the recovery of the highest concentration of these substances [4,7].
The amount of bioactive compounds obtained from extraction processes depends on a
wide variety of factors, ranging from the intrinsic characteristics of the plant of origin, such
as species, variety, genetic composition, geographical location, and environmental and
climatic conditions; cultivation methods; processing methods of the coffee beans, whether
dry, wet, or semi-wet, to the type of product being worked with, whether it is a sample
taken directly from the plant, such as leaves, or working with green or roasted coffee
 that were not naturally present in the plant but are the result of the interaction of its
tabolites, which are physically and chemically modified, giving rise to others, such as
anoidins.
Microorganisms 2025, 13, 215 However, some natural bioactive molecules, such as certain 5phenolic of 20
c
pounds, may also be lost or modified [38,39]. Additionally, the way coffee beverage
prepared beans,
oftenormodifies the content of bioactive compounds present in them [17]. M
with by-products of their processing, such as pulp, mucilage, and bagasse, among
over, experimental work factors also interfere, such as the solvent used for extraction
others [17,36,37].
water, ethanol, Formethanol,
example, the etc., and
roasting the extraction
of coffee beans leads tomethod, whether
the generation of newby agitation, hea
compounds
that were not naturally present in the plant but are the result of the interaction of its
ultrasound, or others. All these factors determine the total content of the compound
metabolites, which are physically and chemically modified, giving rise to others, such
well as their concentration,
as melanoidins. thatsome
However, can natural
be obtained
bioactivefrom coffeesuch
molecules, andasits derivatives
certain phenolic [4].
The enormous
compounds, may amount
also beof waste
lost produced
or modified [38,39].by the coffee
Additionally, theindustry
way coffee has led researc
beverages
are prepared often modifies the content of bioactive compounds present in them [17].
to study it not only for its well-known biological activity but also to explore possible
Moreover, experimental work factors also interfere, such as the solvent used for extraction,
for the by-products generated
like water, ethanol, methanol,during itsextraction
etc., and the processing.
method,These
whetherby-products (Figure 1)
by agitation, heating,
dently retain a considerable
ultrasound, number
or others. All of bioactive
these factors determine thecompounds
total content that
of thecan be utilized,
compounds, as the
well as their concentration, that can be obtained from coffee and
also aiming to mitigate the negative environmental impact caused by their accumula its derivatives [4].
The enormous amount of waste produced by the coffee industry has led researchers to
and improper handling [4].
study it not only for its well-known biological activity but also to explore possible uses for
the by-products generated during its processing. These by-products (Figure 1) evidently
retain a considerable number of bioactive compounds that can be utilized, thereby also
aiming to mitigate the negative environmental impact caused by their accumulation and
improper handling [4].

Figure 1. Internal composition of coffee cherry and by-products.

Figure 1. Internal composition of coffee cherry and by-products.
Coffee By-Products
One of the first waste products that arises after processing green coffee beans is the pulp
Coffee By-Products
(Figure 1). This constitutes approximately 40 to 50% of the fruit’s mass, and its management
after being removed from the cherry usually involves natural decomposition or use as
One fertilizer
of the first
in the waste products
same coffee that arises
fields. However, after processing
this management green
often produces largecoffee
amountsbeans is
pulp (Figure 1). This and
of wastewater constitutes approximately
extremely unpleasant 40constituting
odors, thus to 50% ofathe fruit’s
negative mass,
impact and its m
on the
surrounding
agement after beingenvironment
removed[40,41].
from This
the residue
cherryis composed
usually of carbohydrates,
involves soluble
natural fibers,
decompositio
proteins, and minerals [4]. Coffee pulp has been shown to have a high content of bioactive
use as fertilizer in the same coffee fields. However, this management often produces l
compounds, mainly the following: chlorogenic acid, caffeine, epicatechin, and catechin [42].
amounts of Of wastewater
the aforementionedandcompounds,
extremely unpleasant
chlorogenic acids odors,
constitutethus constituting
approximately 42% ofathe
negative
phenolic acids present in coffee pulp [7]. Other polyphenols, such
pact on the surrounding environment [40,41]. This residue is composed of carbohydras flavonols, flavan-3-ols,
and pigments such as anthocyanidins, have also been reported (Table 1) [43]. The aqueous
soluble fibers, proteins, and minerals [4]. Coffee pulp has been shown to have a high
extract of coffee pulp has been reported to be effective against Gram-positive bacteria such
tent of bioactive compounds,
as Staphylococcus mainly the following: chlorogenic acid, caffeine, epicatec
aureus [40].
and catechin [42]. Of the aforementioned compounds, chlorogenic acids constitute
proximately 42% of the phenolic acids present in coffee pulp [7]. Other polyphenols,
as flavonols, flavan-3-ols, and pigments such as anthocyanidins, have also been repo
(Table 1) [43]. The aqueous extract of coffee pulp has been reported to be effective aga
Gram-positive bacteria such as Staphylococcus aureus [40].
 Microorganisms
Microorganisms2025,
2025,13,
13,xxFOR
FORPEER REVIEW
PEERucts.
REVIEW 66 of
of 21
21

Percentage of
Table 1. Chemical composition,
Chemical bioactive compounds, and percentage of coffee cherry by by-prod-
Microorganisms 2025, 13, 215 By-Products Bioactive Compounds the Coffee Image
Table 1. Chemical
ucts.
Table composition, bioactivecompounds,
Composition compounds, andpercentage
percentageof of coffeecherry
cherry byby-prod-
6by-prod-
of 20
Table1.1.Chemical
Chemicalcomposition,
composition,bioactive
bioactive compounds,and and percentage
Cherry ofcoffee
coffee cherryby
by by-prod-
ucts.
ucts.
ucts. Percentage of
Chemical
By-Products Carbohydrates Bioactive Compounds Percentage
the Coffee of Image
Table 1. Chemical composition,
Composition
Chemical bioactiveChlorogenic
compounds,acid Percentage
and percentage
Percentage of
of coffee
of cherry by by-products.
By-Products Chemical
Chemical Bioactive Compounds the Coffee
Cherry Image
By-Products
By-Products Soluble
Composition fibers Bioactive Caffeine
Bioactive Compounds
Compounds the the Coffee
Coffee Image
Image
Pulp Composition
Chemical
Composition 40–50%
Cherry
Percentage of the
By-Products Proteins
Composition BioactiveEpicatechin
Compounds Cherry
Cherry
Coffee Cherry
Image
Minerals
Carbohydrates Catechinacid
Chlorogenic
Soluble
Carbohydrates
Carbohydrates fibers Caffeine acid
Chlorogenic
Chlorogenic
Pulp Carbohydrates Chlorogenicacid acid 40–50%
Proteins
Carbohydrates
Soluble fibers Chlorogenic acid
Epicatechin
Caffeine
Pulp Soluble
Soluble fibers
fibers Caffeine
Caffeine 40–50%
Pulp Soluble fibers Caffeine 40–50%
Pulp
Pulp Minerals
Proteins
Proteins
Proteins
Catechin
Epicatechin
Epicatechin
Epicatechin 40–50%
40–50%
Proteins
Water Epicatechin
Minerals
Minerals
Minerals Catechin
Catechin
Catechin
Minerals
Carbohydrates Catechinacid
Chlorogenic
Mucilage 14%
Proteins Caffeine
Pectin’s
Water
Water
Carbohydrates
Water Chlorogenic acid
Mucilage Water
Water 14%
Carbohydrates
Proteins
Carbohydrates Chlorogenic
Caffeine
Chlorogenic acid
Mucilage Carbohydrates
Carbohydrates Chlorogenic
Chlorogenic acidacid
acid 14%
Mucilage
Mucilage
Mucilage Proteins
Pectin’s
Proteins Caffeine
Gallic
Caffeine acid
14%
14%
14%
(α)Proteins
Proteins
cellulose Caffeine
Caffeine
Pectin’s
Pectin’s
Pectin’s Chlorogenic acid
Pectin’s
Hemicellulose
Parchment P-cumaric acid 6.1%
Lignin
Sinapic
Gallic acid
acid
Ash
(α) cellulose Caffeine
Chlorogenic
Gallic acid
acid
Hemicellulose
(α)cellulose
cellulose Gallic
Gallic
Gallic acid
acidacid
Parchment (α)
(α)
(α) cellulose
cellulose Chlorogenic
P-cumaric acid
acid 6.1%
Lignin
Hemicellulose
Hemicellulose
Chlorogenic
Chlorogenic
Chlorogenic acidacid
acid
Parchment
Parchment Hemicellulose
Hemicellulose P-cumaric
Sinapic
P-cumaric acid
acid
acid 6.1%
6.1%
Parchment
Parchment Lignin
Ash
Lignin P-cumaric
P-cumaric acid
acid 6.1%
6.1%
Lignin
Lignin
Ash
Gallic
Sinapic
Sinapic acid
acid
Caffeine acid
Ash
Carbohydrates Sinapic
Caffeine
Tannic acid
Sinapicacid
acid
Ash
Ash Caffeine
Husk Fibers Caffeine
Caffeineacid
Chlorogenic 50%
Proteins Epicatechin
Gallic acid
Carbohydrates Caffeine
Tannic
Gallic acid
acid
Gallic
Gallic
Gallic acid
acidacid
Husk Fibers
Carbohydrates
Carbohydrates
Carbohydrates Chlorogenic
Tannic
Tannic
Tannicacid acid
acid
acid 50%
Husk
Carbohydrates Tannic
Caffeine
Chlorogenic acid
acid 50%
Husk Fibers
Proteins
Fibers Epicatechin
Chlorogenic acid 50%
Husk
Husk Fibers
Fibers
Proteins Chlorogenic
Chlorogenic
Epicatechin acid
acid 50%
50%
Proteins Trigonelline
Caffeine
Epicatechin
Proteins
Dietary
Proteins fiber Epicatechin
Caffeine
Epicatechinacid
3-feruloylquinic
Caffeine
Polysaccharides Caffeine
Caffeine acid
5-caffeoylquinic
Caffeine
Silver skin Proteins 4.2%
3-caffeoylquinic
Caffeine acid
Trigonelline
Caffeine
Fats
Dietary fiber Caffeine
Caffeineacid
Trigonelline
Dietary fiber Chlorogenic
3-feruloylquinic
Trigonelline acid
Ash
Dietary
Polysaccharides Trigonelline
fiber 3-feruloylquinic
Trigonellineacid
Dietary
Polysaccharides fiber P-cumaric acid
5-caffeoylquinic
Dietary fiber 5-caffeoylquinic
3-feruloylquinic acidacid
acid
Silver
Silver skin Polysaccharides
skin Polysaccharides
Proteins
Proteins 3-feruloylquinic
3-feruloylquinic acid
acid 4.2%
4.2%
Polysaccharides
Fats Melanoidins
3-caffeoylquinic
3-caffeoylquinic
5-caffeoylquinic acidacid
acid
Silver skin Proteins
Fats 5-caffeoylquinic
5-caffeoylquinic
Chlorogenic acid acidacid 4.2%
Silver
Silverskin
skin Proteins
Ash
Proteins Chlorogenic
3-caffeoylquinic acidacid 4.2%
4.2%
Fats
Ash 3-caffeoylquinic
P-cumaric acid
3-caffeoylquinic acidacid
Fats
Fats Caffeic acid
P-cumaric
Chlorogenic
Melanoidins acid
acid
Ash Chlorogenic
Chlorogenicacid acid
Ash
Ash Gallic acid
Melanoidins
P-cumaric acid
Chlorogenic
P-cumaric acid
acid
P-cumaric acid
Ferulic
Caffeic acidacid
Melanoidins
Chlorogenic
Melanoidins acid
Melanoidins
Gallic acid
Polysaccharides Ellagic
Caffeic
Chlorogenic acidacid
Ferulic acid acid
Chlorogenic
Chlorogenic acid
Proteins
Polysaccharides P-coumaric
Ellagic acid
Caffeic
Gallic acid
acid
acid
Proteins Caffeic
P-coumaric acid
Caffeicacid
acid
Minerals
Minerals Protocatechuic
Gallicacid
Ferulic acid 90% of the
Spent
Spent coffee
coffee Gallic
Protocatechuic
Gallic acid 90% of the initial
Fats
Fats
Polysaccharides Tannic
Ferulic
Tannic acidacid
acid
Ellagic acid initial
coffee coffee
beans
grounds
grounds Dietary fiber Ferulic
Ferulic
Catechin acid
Dietary
Proteins
Vitamin fiber
Polysaccharides
E Catechin
Ellagic
P-coumaric
Epicatechin acid
acid beans
Polysaccharides
Polysaccharides Ellagic acid
Ellagic acid
Vitamin
Lignin
Proteins
Minerals E Epicatechin
P-coumaric
Quercetin
Protocatechuic acid 90% of the
Spent coffee Proteins
Proteins P-coumaric
P-coumaric
Rutin acid
acid
Lignin
Minerals
Fats Quercetin
Protocatechuic
Tannic acid
Trigonelline 90% coffee
initial of the
grounds
Spent coffee Minerals
Minerals Protocatechuic
Protocatechuic 90%
90%of ofthe
the
Spent coffee
Spent coffee Dietary Fats fiber Rutin
Tannic
Caffeine
Catechin acid initial
beans coffee
grounds Fats
Fats Tannic
Tannic
Melanoidins acid
acid initial
initial coffee
coffee
grounds
grounds Dietary
Vitaminfiber E Trigonelline
Catechin
Epicatechin beans
Dietary
Dietaryfiber fiber Catechin
Catechin beans
beans
Vitamin
Lignin E Caffeine
Epicatechin
Quercetin
Vitamin
VitaminEE Epicatechin
Epicatechin
Mucilage (FigureLignin 1) is another ofMelanoidins
Lignin Quercetin
the Rutin
initial residues obtained when coffee beans are
Quercetin
Lignin Quercetin
removed from the cherry, constituting around Trigonelline
Rutin
Rutin14% of the fruit’s dry weight. It is removed
Rutin
Caffeine
Trigonelline
from the beans through a fermentation Trigonelline process that usually lasts from 24 to 72 h. It is mainly
Trigonelline
Melanoidins
Caffeine
Caffeine
composed of water, proteins, carbohydrates, and pectins and has a considerable content of
Caffeine
Melanoidins
Melanoidins
phenolic compounds (Table 1) [44]. Mucilage Melanoidins
is a waste generated in large quantities from
coffee processing, with an estimated 56 kg of mucilage produced for every 60 kg bag of
green coffee beans [45]. Among the bioactive compounds found in this product, chlorogenic
acid and caffeine are noteworthy, particularly in ethanol extract. This same extract has been
shown to be effective against Gram-positive bacteria such as Bacillus cereus [7].
Microorganisms 2025, 13, 215 7 of 20

The parchment (Figure 1) consists of the fibrous endocarp that covers the coffee beans
and keeps them separated. It represents approximately 6.1% of the fruit, being found in
lesser quantities than the pulp and mucilage [46]. This by-product is mainly composed of
(α) cellulose, hemicellulose, lignin, and ash; however, it also has a significant content of
bioactive compounds that remain even after being separated from the coffee cherry [47].
For every 100 kg of green coffee beans produced, approximately 18 kg of this residue is
obtained [4]. Usually, this product is treated by producing pressed pellets used for energy
generation, which are obtained or released by burning them. However, the improper
management of this residue still represents a significant environmental threat, as it is
necessary to find other ways to utilize or eliminate it more effectively and in line with the
amount produced. This applies to any waste obtained from the coffee industry [46]. For
parchment, phenolic compounds such as gallic acid, chlorogenic acid, p-coumaric acid, and
sinapic acid, as well as alkaloids like caffeine, have been reported in an optimized (70%)
ethanol extract (Table 1). These compounds have already been shown to contribute to the
antimicrobial activity of coffee [47].
The combination of the three previously described residues, pulp, mucilage, and
parchment, along with the skin, is known as coffee husk. This is the main waste obtained
from the dry processing of green beans, representing approximately 50% of the fruit’s dry
weight [4]. The coffee husk is mainly composed of carbohydrates, around 85%, and fibers
and proteins. However, it has also been shown to have a significant number of bioactive
compounds such as gallic acid, tannic acid, chlorogenic acid, epicatechin, and caffeine
(Table 1) [48–50]. Usually, coffee husk residues are burned or used as compost; however,
most of these are simply discarded without any specific or adequate treatment, which
eventually becomes a source of environmental pollution [48,51].
On the other hand, silverskin (Figure 1) is a residue obtained during the roasting
process of green coffee beans. It is a thin layer that directly covers the seeds [52]. This
component of coffee is mainly composed of dietary fiber, polysaccharides, proteins, fats,
and ash. However, it also has a significant number of bioactive compounds, mainly
of an antioxidant nature, and represents approximately 4.2% of the coffee cherry [4,53].
In silverskin, bioactive compounds such as caffeine, trigonelline, 3-feruloylquinic acid,
5-caffeoylquinic acid, and 3-caffeoylquinic acid, which are isomers of chlorogenic acid, and
p-coumaric acid have been observed in aqueous extracts obtained through a hydrodistil-
lation process. Melanoidins can also be found since these are formed during the coffee
roasting process, which is when this coating is removed, thus retaining some of these
molecules (Table 1) [54,55].
Studies on coffee and its biological potential are not solely focused on extracts from
derived products; they also analyze the properties and content of secondary metabolites
present in both green and roasted coffee beans. The coffee roasting process alters the content
and quantity of the compounds present. Therefore, understanding these differences helps
to better understand which specific molecules can be obtained from both resources and
what their most suitable application is. Additionally, the degree of roasting of the beans
produces variations in the content of bioactive compounds [39]. Among many factors, the
phytochemical composition of green coffee beans depends on their genetic load and degree
of ripeness. It has been observed that the content of caffeine, trigonelline, and chlorogenic
acids tends to be higher in green coffee [37]. In the case of chlorogenic acid, its concentration
decreases during the roasting process due to exposure to high temperatures, resulting in
the breakdown of the molecule into its components, caffeic acid and quinic acid. However,
the degree of roasting also influences the content of chlorogenic acid. Light roasting retains
a large amount of this compound, while darker roasting results in a lower concentration of
chlorogenic acid [5]. Nevertheless, its presence after roasting remains significant, as it has
 its concentration decreases during the roasting process due to exposure to high tempera-
tures, resulting in the breakdown of the molecule into its components, caffeic acid and
quinic acid. However, the degree of roasting also influences the content of chlorogenic
Microorganisms 2025, 13, 215 acid. Light roasting retains a large amount of this compound, while darker roasting results 8 of 20
in a lower concentration of chlorogenic acid [5]. Nevertheless, its presence after roasting
remains significant, as it has been estimated that coffee provides the majority of chloro-
been
genic estimated
acids in the that
diet coffee
in many provides
regions, the majority
which of chlorogenic
is linked to the high acids in the dietof
consumption in this
many
product [18]. Chlorogenic acids are estimated to represent 6 to 12% of the dry weight ofare
regions, which is linked to the high consumption of this product [18]. Chlorogenic acids
estimated
green coffee to represent
seeds, making 6 tothem
12% the
of the drysource
main weightofofchlorogenic
green coffeeacids seeds,
in making them the
nature [18,56].
main source of chlorogenic acids in nature [18,56]. Alamri et al. (2022)
Alamri et al. (2022) found no significant differences in caffeine levels depending on the found no significant
differences
degree in caffeine
of roasting (light,levels
medium,depending on the
and dark), degree
with of roasting
values being quite(light, medium,
similar amongand dark),
sam-
with values being quite similar among samples of Arabica coffee beans.
ples of Arabica coffee beans. Roasting beans leads to the formation of other bioactive com- Roasting beans
leads to
pounds, theas
such formation
melanoidins,of other
whichbioactive compounds,
have been shown to suchhave as melanoidins,
a wide which have
range of biological
been shown to have a wide range of biological properties [39]. Freitas
properties [39]. Freitas et al. (2024) found a higher content of melanoidins in robusta coffeeet al. (2024) found a
higher content
compared of melanoidins
to C. arabica. in robusta
Activity against coffee compared
Gram-positive to C. arabica. Activity
and Gram-negative bacteriaagainst
has
Gram-positive and Gram-negative bacteria
been reported for both green and roasted coffee beans [38]. has been reported for both green and roasted
coffee beanscan
Extracts [38].
also be obtained directly from the plant (Figure 2), such as from leaves.
Extracts
Yosboonruang et canal.also be obtained
(2022) determined directly
the from the plant
presence (Figure 2),
of bioactive such as from
compounds suchleaves.
as
chlorogenic acid and caffeine in a leaf extract of C. canephora, and they also analyzed its as
Yosboonruang et al. (2022) determined the presence of bioactive compounds such
chlorogenic acid and caffeine in a leaf extract of C. canephora, and they also analyzed its
antibacterial properties against Gram-positive and Gram-negative bacteria. They were
antibacterial properties against Gram-positive and Gram-negative bacteria. They were
found to be particularly effective against Bacillus subtilis and Staphylococcus aureus, known
found to be particularly effective against Bacillus subtilis and Staphylococcus aureus, known
pathogens transmitted through food [8].
pathogens transmitted through food [8].

Figure
Figure 2. Coffee
2. Coffee plant
plant with
with mature
mature cherries.
cherries.

Finally, the last residue produced in the coffee industry is the spent coffee grounds,
Finally, the last residue produced in the coffee industry is the spent coffee grounds,
as they are obtained directly from the preparation of coffee beverages. It is estimated that
as they are obtained directly from the preparation of coffee beverages. It is estimated that
around 6 million tons of spent grounds are produced annually, with 50% coming from the
around 6 million tons of spent grounds are produced annually, with 50% coming from the
commercial preparation of coffee in cafeterias and the remaining 50% from the industrial
commercial preparation of coffee in cafeterias and the remaining 50% from the industrial
production of soluble coffee. This residue constitutes 90% of the initial coffee beans [2,52,57].
production of soluble coffee. This residue constitutes 90% of the initial coffee beans
Spent grounds are mainly composed of polysaccharides, proteins, minerals, fats, dietary
[2,52,57]. Spent grounds are mainly composed of polysaccharides, proteins, minerals, fats,
fiber, vitamin E, and lignin [16]. It has been reported that spent ground coffee extracts
dietary fiber, vitamin E, and lignin [16]. It has been reported that spent ground coffee
contain phenolic compounds such as chlorogenic, caffeic, gallic, ferulic, ellagic, p-coumaric,
protocatechuic, and tannic acids, as well as catechin, epicatechin, quercetin, and rutin, and
alkaloids such as trigonelline and caffeine when polar or moderately polar solvents, such
as ethanol and methanol, are used in combination with deionized water (Table 1). It is
also rich in melanoidins and diterpenes such as cafestol and kahweol [16,54,58–60]. Like
many of the aforementioned residues, spent coffee grounds also retain significant amounts
of environmentally harmful compounds, which can cause significant damage to soil and
water near the deposition site, as organic compounds require large amounts of oxygen for
decomposition. Badr et al. (2022) found that isopropanolic extract from spent grounds
Microorganisms 2025, 13, 215 9 of 20

could inhibit the development of pathogenic bacteria such as Escherichia coli and fungi such
as Aspergillus. Therefore, finding ways to reuse this product is a paramount task [2,61,62].

4. Antimicrobial Activities of Coffee and Its By-Products

Antimicrobials are compounds that have the ability to kill or inhibit the growth of
microorganisms, such as fungi and bacteria [4]. As mentioned throughout this work, coffee
has demonstrated a significant antimicrobial effect, and it is considered that this property is
conferred by the bioactive compounds that compose it, mainly by the phenolic compounds
and alkaloids described earlier. The following will present the antimicrobial mechanisms
found in these compounds and will also mention the most recent research on the antimicrobial
effect of coffee, as well as its derivatives, against bacteria, fungi, and viruses.

4.1. Antibacterial Activity of Coffee and Its By-Products

Canci et al. (2022) analyzed the antibacterial potential of an aqueous extract of roasted
and green coffee (C. arabica and C. canephora) against pathogenic bacteria, calculating the
minimum inhibitory concentration (MIC) of their extract and conducting a time kinetics test
for microorganisms susceptible to the first test. In this case, they found that the bacteria
sensitive to their extracts were Salmonella typhimurium and E. coli, both Gram-negative bacteria.
However, no effect was observed on the bacteria Lactobacillus plantarum and Lactobacillus
rhamnosus, which are known to be probiotic microorganisms. This may be due to the selective
effect of the bioactive compounds, which can promote the growth of certain bacteria and
inhibit the growth of others. This effect has been reported for chlorogenic acid and caffeic
acid, both of which have been shown to have antibacterial and probiotic effects. In the case of
the latter, it has been observed that the unabsorbed portion of these compounds serves as a
substrate for beneficial bacteria inhabiting the gastrointestinal tract [63].
Yosboonruang et al. (2022) analyzed the antibacterial effect present in an aqueous
extract of C. canephora leaf by calculating the MIC and conducting the agar well diffusion test.
In this case, they found that their extract was particularly effective against S. aureus with
an MIC of 6.25 mg/mL and for Bacillus subtilis, E. coli, and S. typhimurium with an MIC of
12.5 mg/mL for each of these strains. Other bacteria, such as Bacillus cereus and Pseudomonas
aeruginosa, also proved susceptible, but at much higher concentrations, 50 and 25 mg/mL,
respectively. These bacteria are known to be foodborne pathogens, so the effectiveness of
coffee compounds as antibacterials may be useful in food preservative production. They
also conducted a test to evaluate the integrity of the bacterial cell membrane, where they
reported observing leakage of intracellular material, namely nucleic acids and proteins.
The loss of these molecules inhibits protein production and DNA synthesis, eventually
leading to the death of the microorganism [8].
Chaves-Ulate et al. (2023) tested the antimicrobial potential of an ethanolic extract
of coffee mucilage on bacteria associated with the deterioration of certain foods and with
human intestinal microbiota. In this case, the authors reported that their extract successfully
inhibited the growth of Gram-positive bacteria such as B. cereus, Listeria monocytogenes,
Micrococcus luteus, and S. aureus. However, the same result was not observed in Gram-
negative bacteria such as E. coli, Salmonella sp., Alcaligenes sp., and Pseudomonas sp. The
technique used to evaluate the antibacterial activity of the extract was agar microdilution,
and the bacterium most susceptible to this extract was B. cereus. The authors discuss that
the difference in the inhibition effect of the extract regarding bacterial groups may be
due to the structural differences between the two types, as Gram-negative bacteria have
an outer membrane with lipopolysaccharides, which provides greater protection against
antibacterial compounds. It has been observed that some low molecular weight phenolic
compounds have the ability to penetrate the cell membrane, causing the acidification
Microorganisms 2025, 13, 215 10 of 20

of the cytoplasm, which consequently leads to bacterial death, making Gram-negative

microorganisms more resistant to this mechanism. It is also considered that the inhibitory
effect is closely related to the concentration of the extract, so at higher concentrations, not
considered in this study, a different result could be observed [7].
Zubair (2024) analyzed the antibacterial activity of various aqueous extracts of coffee
from C. arabica against biofilm-forming bacteria associated with diabetic foot ulcers. MIC
tests showed that the most effective extract against strains of P. aeruginosa, E. coli, and S.
aureus was powdered green coffee extract, with MIC values of up to 300 µL/mL. Tests were
also conducted to observe the inhibitory effect on biofilm formation by coffee extracts using
MIC sublevels (1/2xMIC and 1/16xMIC) in monocultures. Biofilm formation inhibition
was evaluated using the quantitative method on flat-bottomed 96-well plates (microtiter
plates). The powdered green coffee extract showed a biofilm inhibition level of 76% for
P. aeruginosa, 62% for E. coli, and 53% for S. aureus on average. Meanwhile, roasted coffee
bean extracts and spent coffee powder extracts yielded inhibition percentages of 66%, 53%,
and 51%, respectively, for the same bacteria. For mixed cultures, the most effective sample
was found to be the green coffee extract, with inhibition percentages of 66% (1/2xMIC),
56% (1/4xMIC), and 17% (1/8xMIC). Based on the previous results, it was determined
that the ground green coffee extract was the most promising in terms of antibacterial
activity, and therefore, it was selected for further tests. One of these tests consisted of
evaluating membrane integrity; for this, an N-Phenyl-1-naphthylamine (NPN) uptake
assay was conducted to evaluate the disruption of the bacteria’s outer membrane. Under
normal conditions, the NPN compound cannot enter the cell due to the outer membrane;
however, when this is disrupted, NPN can infiltrate the lipid bilayer, being detected through
fluorescence emission, which increases when it is inserted into the membrane. In this case,
the study reports an increase in NPN uptake of 51% in P. aeruginosa, 41% in E. coli, and
48% in S. aureus. In mixed strains, an average increase of 45% was observed. Disrupting
the continuity of the outer membrane provides coffee with a highly important tool for
inhibiting biofilm formation, as altering the integrity of the bacterial outer membrane may
reduce its adhesion power and ability to bind to certain surfaces [64].
Jamalifar et al. (2019) studied the regulatory effects of green coffee extract on genes
associated with the virulence of P. aeruginosa. This bacterium is notable for having strains
resistant to various antibiotics, which they achieve through the action of two genes, las I and
las R, which provide the microorganism with increased pathogenicity and more aggressive
mechanisms against the affected person. This bacterium usually infects individuals with
weakened immune systems, such as those suffering from conditions like cancer or AIDS. To
collectively regulate the expression of these genes, these bacteria use the quorum sensing
(QS) mechanism, which can lead to biofilm formation, toxin production, and other drug or
antibacterial resistance systems. Therefore, one way to combat its development is to alter or
stop this mechanism. In this study, the aim was to determine whether green coffee extract
served as a good preventive measure for the expression of these genes, thus reducing
the development and spread of antibiotic-resistant microorganisms. To determine this,
a real-time PCR procedure was carried out, resulting in a 0.49 to 0.75 times reduction
in the expression of these genes in the presence of green coffee extract, compared to the
control samples, which did not receive the extract. This confirms the suspicion that the
compounds present in coffee, particularly green coffee in this specific case, are capable
of inhibiting biofilm development and other resistance mechanisms by decreasing the
expression of the aforementioned genes. The authors attribute this antibacterial effect to
phenolic compounds, particularly chlorogenic acid [65].
In a field similar to the previously analyzed study, Rawangkan et al. (2023) tested
various aqueous extracts of coffee (C. arabica) to assess their antibacterial effect against
Microorganisms 2025, 13, 215 11 of 20

multidrug-resistant strains of E. coli and also evaluated their potential as an adjuvant to

the antibiotic ampicillin for treating diseases caused by this microorganism. Currently,
ampicillin is not recommended for infections caused by E. coli, as most strains of this agent
show resistance; therefore, this work focuses on finding a natural alternative that works
on its own or can at least enhance the effect of the antibiotic. In this case, three different
extracts were tested: dried green coffee beans, coffee pulp, and crude extracts from C. arabica
leaves. These were subjected to MIC and minimum bactericidal concentration (MBC) tests
individually on 28 multidrug-resistant E. coli strains. It was found that the most effective
extract against these microorganisms was coffee pulp, with MICs ranging from 12.5 mg/mL
to 50 mg/mL. Subsequently, a test was conducted to evaluate the combined effect of each
coffee extract with ampicillin. In these analyses, it was found that only the combination of
coffee pulp extract and ampicillin was effective at the antibacterial level, yielding an MIC of
0.02 mg/mL, while the MIC of the drug alone was 50 mg/mL, demonstrating that an agro-
industrial byproduct of coffee production, such as pulp, in combination with an antibiotic,
is a promising alternative to combat diseases caused by multidrug-resistant bacteria. To
reinforce the previous findings, a bactericidal kinetics test was conducted, comparing the
pulp extract and the antibiotic separately, as well as in combination. It was found that coffee
pulp extract exerts bactericidal activity at concentrations of 50 mg/mL and 100 mg/mL in
20 and 7 h, respectively. Ampicillin, on the other hand, had a bactericidal effect after 4 h at
a concentration of 50 mg/mL. However, the combination of the extract with ampicillin at
a concentration of 0.2 mg/mL of extract and 0.01 mg/mL of antibiotic had a bactericidal
effect in 3 h, improving the drug’s action time and at much lower concentrations. Some
standards of the bioactive compounds reported in coffee and its derivatives were also
tested, including caffeine, chlorogenic acid, and caffeic acid, of which caffeine exhibited the
greatest bacteriostatic effect individually [66].

4.2. Antifungal Activity of Coffee and Its By-Products

In 2022, Badr et al. analyzed the antifungal effect of an isopropanolic extract from
spent coffee grounds on fungi that produce mycotoxins, such as those from the genera
Aspergillus, Fusarium, and Penicillium. For this, they used the disk diffusion and well
diffusion techniques, both of which are fairly standard procedures when investigating
compounds with antimicrobial potential. In this case, they found that all the analyzed
strains were susceptible to the effects of the bagasse extract, with relatively similar values
across the different species treated, as they all exhibited approximately 50% of the effect
observed in the antifungal amphotericin B used as a control. Additionally, an experiment
was conducted to assess the reduction in mycelial growth of two toxin-producing strains
from the Aspergillus genus. For this, liquid culture media were used to simulate the effect
of fungal contamination in food as it naturally occurs in the environment. The results
showed a concentration-dependent decrease in mycelial growth, meaning that at higher
concentrations, up to 4 mg/mL, the inhibitory effect was also greater. Furthermore, the
extract’s ability to reduce mycotoxin production, particularly aflatoxins and ochratoxins in
liquid media, was evaluated. It was found that the anti-toxin effect was also concentration-
dependent: the higher the concentration, the lower the toxin production. The results from
this research indicate the potential of spent coffee grounds as a food preservative, helping
to maintain product safety by keeping them free from mycotoxins. Additionally, it offers
the possibility of reusing an agro-industrial byproduct that is usually considered a source
of environmental pollution [67].
Barbero López et al. (2020) conducted a study to evaluate the valorization of coffee
silverskin as a material with antifungal properties, focusing on its application in wood
preservation, as wood is commonly infected by fungi and traditional preservatives are
Microorganisms 2025, 13, 215 12 of 20

often harmful to the environment. In this study, they used an aqueous extract of coffee
silverskin and tested its antimicrobial activity on three fungal strains that cause wood
rot: Rhodonia placenta, Gloeophyllum trabeum, and Trametes versicolor. In the antifungal
activity tests, the authors found that the 3% silverskin extract was able to inhibit the
growth of all three fungi by more than 60%. Toxicity tests were also carried out to assess
whether the silverskin extract is truly viable for use as an adjunct to wood preservatives
without causing negative environmental effects. The acute ecotoxicity test of the extract was
performed on photoluminescent bacteria of the species Aliivibrio fischeri, aiming to observe
a reduction in bioluminescence after a 30 min period. This analysis found that the extract
had relatively low ecotoxic effects, with an EC50 (50% effective concentration) of 2661 mg/L
and an EC20 (20% effective concentration) of 1172 mg/L, whereas a common copper-based
wood preservative showed higher ecotoxicity, with an EC50 of 19 mg/L and an EC20 of
12 mg/L. In this case, EC50 and EC20 are measures used to evaluate the toxicity of a
chemical compound, where lower values indicate higher levels of toxicity. The authors
suggest that silverskin extract could function as an additive or a complement to traditional
wood preservatives [68].
Calheiros et al. (2023) conducted a study to evaluate the antifungal activity of extracts
from coffee bagasse, both caffeinated and decaffeinated, focusing primarily on pathogenic
fungi that infect human skin. To determine fungal susceptibility to the extract, they per-
formed the commonly used MIC test (minimum inhibitory concentration) using the broth
microdilution technique. This study focused on yeasts and filamentous fungi. They also
calculated the minimum fungicidal concentration (MFC), which estimates the lowest con-
centration of the tested compound that can produce 99% fungal cell death. The strains most
susceptible to the analyzed extracts were Candida krusei, Candida parapsilosis, Trichophyton
mentagrophytes, and Trichophyton rubrum, with the extract from caffeinated coffee bagasse
proving to be particularly more effective than that from decaffeinated coffee, which resulted
in higher MIC values. Both extracts exhibited fungicidal effects on T. mentagrophytes and T.
rubrum. To attempt to elucidate the mechanism of action of the coffee bagasse extracts on
the fungal cell membrane, they evaluated ergosterol and chitin content after applying the
extracts and compared it to untreated fungal cells. These compounds are basic structural
components of fungal cell membranes, and their reduction or loss indicates the level of
damage caused by the extracts. In this test, significant differences (p < 0.01) were found
in ergosterol and chitin percentages only for C. parapsilosis when applying the caffeinated
coffee bagasse extract. Notably, the ethanolic coffee bagasse extract produced the best
results compared to aqueous extracts [69].
Sangta et al. (2021) sought to find ways to valorize coffee pulp, as this agro-industrial
waste is produced in large quantities and its disposal poses a challenge. For this study,
the authors used a methanolic extract of coffee pulp. Various concentrations of the extract
were selected to evaluate its antifungal activity against agriculturally important fungi,
particularly horticultural pathogens. These concentrations were 0.01, 0.03, 0.05, 0.1, and
0.5 g/mL. The antifungal effect observed in this study was concentration-dependent, mean-
ing that higher concentrations resulted in greater inhibition of fungal growth in vitro on
Petri dish culture media. The 0.5 g/mL concentration was the most effective against Al-
ternaria brassicicola, Pestalotiopsis sp., and Paramyrothecium breviseta, with the latter showing
the greatest susceptibility to the coffee pulp extract, exhibiting a 78% reduction in growth.
This study proposes and opens the possibility of reusing agro-industrial waste from coffee
production for the control of agricultural diseases caused by phytopathogenic fungi [70].
Microorganisms 2025, 13, 215 13 of 20

4.3. Antiviral Activity of Coffee and Its By-Products

Coffee, caffeine, and naturally caffeinated beverages are well known for their biological
capacity and ability to confer various health benefits, including disease prevention. The
alkaloid caffeine present in coffee extracts has demonstrated antiviral activity against herpes
simplex virus type 1 [71]. In a study by Batista et al. (2015), it was found that caffeine
inhibited hepatitis C virus (HCV) replication in a dose-dependent manner at non-cytotoxic
concentrations, with an IC50 value of 0.7263 mM after 48 h of incubation [72]. Additionally,
caffeine consumption from coffee has been associated with a reduction in viral load in
hepatitis C patients and an increased tolerance to peginterferon and ribavirin treatment [73].
In addition to caffeine, the coffee extracts of coffee beans contain significant amounts of
chlorogenic acid, which are the major soluble phenolic compounds (Figure S2b). A single
cup of coffee may contain 70–350 mg of chlorogenic acid [74]. Consequently, chlorogenic
acids and their hydrolysates, which are the main components of the phenolic fraction of
coffee beans, have been extensively studied for their antiviral properties [74].
Naturally caffeinated beverages have also been recognized for their broad health
benefits. Caffeic acid has been found to have an antiviral effect against the DNA virus
(herpes virus HSV) and the non-enveloped RNA virus (polio virus), suppressing virus-
infected cell degeneration [75]. Furthermore, regular coffee consumption (more than three
cups per day) has been associated with antiviral activity in the human immunodeficiency
virus (HIV) and the hepatitis C virus (HCV) [76,77]. According to Shen et al. (2018), caffeic
acid can inhibit HCV replications through the induction of heme oxygenase-1, which
triggers the antiviral response involving interferon-alpha (IFNα). This antiviral effect is
attenuated when HO-1 activity is inhibited by SnPP (an HO-1 inhibitor) [78]. Additionally,
Tanida et al. (2015) found that caffeic acid inhibited the initial stage of HCV infection
(i.e., between virion entry and translation of the RNA) [79].
In vitro and in vivo studies using crude coffee beans extracts rich in chlorogenic acid,
quinic acid, and caffeic acid, have demonstrated substantial inhibitory activity against
hepatitis B virus DNA (HBV-DNA) replication in HepG2.2.15 cells [80]. Other studies
using aqueous extracts of coffee have shown a notable suppressive effect on hepatitis B
virus surface antigens. This biological activity was closely related to the presence of caffeic
acid derivatives, especially chlorogenic acid. The suppression of HBV-DNA replication
caused by chlorogenic and quinic acids may involve mechanisms such as the inhibition of
pgRNA transcription, the capsid encapsulation process, and the disruption of polymerase
transcription activity. Additionally, caffeic acid may interfere with the viral maturation
pathway [74,81].
The antiviral activity of coffee extract derivates has also been studied in respiratory
viruses. Moderate coffee consumption, including decaffeinated coffee, could offer a new
guideline for the prevention of SARS-CoV-2 infection. Coffee compounds have been shown
to inhibit the binding of the SARS-CoV-2 spike protein to the host ACE2 receptor and reduce
the activity of TMPRSS2. Based on the results, researchers suggest that incorporating coffee
into the diet may serve as a preventive strategy in the post-COVID-19 era [10].
The Center for Disease Control and Prevention (CDC) recommends caution when
consuming caffeine, particularly in energy drinks, due to potential adverse effects at high
doses (CDC, 2024). While moderate caffeine intake from coffee may offer health benefits,
excessive consumption can lead to overstimulation and cardiovascular issues, potentially
outweighing any antiviral effects [82].
Coffee by-products, such as coffee leaves, coffee pulp, coffee husks, silver skin, spent
coffee grounds, and other manufacturing industry products, reveal an excellent profile
of biological compounds. Behne et al. (2023) identified 5-caffeoylquinic acid (5-CQA)
and 3,5-dicaffeoylquinic acid (3,5-DCQA) as the predominant chlorogenic acids in coffee
Microorganisms 2025, 13, 215 14 of 20

by-products [83]. On the other hand, Wu et al. (2022), found that concentrated coffee
leaf extract applied to the skin surface could block SARS-CoV-2 from entering cells more
effectively than 75% ethanol, a standard disinfectant recommended by the World Health
Organization (WHO) for inactivating SARS-CoV-2 [84].
Most antiviral research has focused on coffee extracts, specifically on their phenolic
and alkaloid compounds. Fewer studies have explored the antiviral properties of coffee
by-products. Given the growing threat of viral infections, particularly respiratory viruses such
as COVID-19, there is an urgent need for alternative strategies to mitigate the transmission of
viral variants (i.e., SARS-CoV-2 variants). In this context, exploring the antiviral potential of
coffee by-products could provide a viable and sustainable approach to combat viral diseases.

5. Regarding the Future of Coffee Residues as a Sustainable Alternative

for Antimicrobials Used in Agronomic Practices
As discussed throughout this work, the coffee industry generates a large amount of
waste products that contribute to environmental pollution. However, all these residues
retain many of the phytochemical properties of the original coffee plant and can therefore
be revalued and utilized in various sectors. This review has analyzed articles focused on
the reuse of these wastes as a source of bioactive compounds, which exhibit antimicrobial
properties. Nevertheless, these studies have been primarily directed toward the healthcare
and food sectors, overlooking other areas or sectors that could also benefit from these
properties. One such area is the agricultural sector, which is commonly affected by bacterial,
fungal, and viral phytopathogens that threaten crop integrity. The usual treatments for
these pathogens are often ineffective or harmful to the environment or public health.
Bacterial phytopathogens, in particular, cause losses of up to a billion dollars annu-
ally, primarily affecting fruit crops such as pear and apple orchards or even vineyards.
Antibiotics are commonly used as treatment or prevention for diseases caused by these
microorganisms, with the most used in this sector being streptomycin, gentamicin, oxyte-
tracycline, kasugamycin, and oxolinic acid. Of these, kasugamycin is the only antibiotic
not used in the healthcare or veterinary sectors [85]. This presents a significant issue, as
bacteria can acquire resistance genes and mechanisms and transfer them to other bacteria
that lack them. This is relevant because the use of healthcare antibiotics in agriculture
may promote the development of antibiotic resistance in phytopathogenic bacteria, which,
when interacting with human or animal pathogens in the environment, could transfer this
resistance, thus affecting the efficacy of these medications in clinical and health-related
conditions. This underscores the need to seek new substances with bacteriostatic or bac-
tericidal effects, as it is expected that most of the antibiotics currently in use will become
obsolete in treating many diseases in the future. Antibiotics are typically applied to crops
as ingredients in pesticides, administered preventively or after disease detection. However,
there is little control over the actual amount of antibiotics being applied, as it is a poorly
regulated process. Despite the belief that their use in agriculture is minimal, this lack
of control suggests a wider spread of these drugs than anticipated. Bacterial resistance
to streptomycin in phytopathogenic strains has been reported since the 1940s, shortly
after its approval for use in crops in 1943. America and Asia are the only continents with
authorization for the use of antibiotics in controlling bacterial diseases in crops [6,85,86].
The use of antibiotics in crops is so poorly controlled that many farmers apply them
to nematode or mite infestations, which are not affected by these substances designed
specifically for bacterial control. As a result, these antibiotics are being unnecessarily
exposed to the environment, potentially affecting the persistence and development of soil
microflora, which promote plant growth and facilitate nutrient absorption. Another method
to mitigate the impact of bacterial diseases is the use of copper salts. However, this also
Microorganisms 2025, 13, 215 15 of 20

poses a problem, as it promotes the development of bacteria resistant to this metal. It has
been observed that metal-resistant bacteria are more likely to acquire antibiotic resistance
genes, meaning this cannot be considered an optimal alternative either [6,86].
On the other hand, fungicides are a class of pesticides used in the agricultural sector
to prevent or stop diseases caused by fungi in cultivated plants. The most used compounds
as fungicides in agriculture are copper, dithiocarbamates, and triazoles/diazoles. Of these,
only triazoles/diazoles are used to treat fungal infections in the healthcare and veterinary
sectors, in addition to being widely used in Europe to control fungal diseases in crops.
Globally, fungicides are the second most widely used class of pesticides in agricultural
disease control, accounting for around 23% of pesticide sales [6,87]. Like antibiotics and
other antimicrobial compounds, fungicides also promote the evolution of microorganisms
and the development of resistance to these compounds, which, in the case of medications
also used in human and animal medicine for the same purpose, represents a problem nearly
as serious as bacterial resistance [6]. This highlights the importance of seeking alternative
compounds to mitigate the impact of fungal infections in crops.
In the case of viral phytopathogens, no effective treatment has been found to mitigate
the impact of the diseases they cause in crops. In other words, there is no specific substance
with a virucidal effect. Instead, strategies have been employed to help manage the associ-
ated plant pathologies. Viruses are intracellular pathogens that typically reach plants with
the help of vectors, mostly insects like flies or aphids. These vectors acquire the viruses
when they come into contact with an infected plant and spread the pathogen when they
“deposit” the virus in a healthy plant [88]. The most commonly used strategy for controlling
viral infections in crops is pest control, which involves using products to prevent potential
virus-carrying vectors from approaching the plants, such as insecticides. However, this
technique proves to be ineffective and continues to result in millions of dollars in losses in
the agricultural sector. The most effective technique for controlling viral diseases in crops
is the use of seeds or plants with the genetic tools necessary to combat the pathology. This
means cultivating plants that are genetically resistant to these viruses, ensuring that the
disease does not affect them or spread to neighboring plants [89]. Another commonly used
strategy is crop rotation, which involves not planting the same crops consecutively, aiming
to prevent vectors that may have approached crop one from containing a virus that could
infect crop two [89]. Despite the implementation of these strategies, the lack of a specific
and precise treatment for the various viral phytopathogens that plague many of the crops
that society relies on for food remains a significant problem. None of these strategies are
effective enough to fully control the spread of a viral disease.
In this sense, it becomes clear how agriculture could greatly benefit from the bioactive
compounds present in coffee products and by-products, which, in various instances, have
already demonstrated inhibitory effects on the growth of these three classes of pathogens.
The application of bioactive compounds derived from the coffee plant could offer a more
effective treatment for controlling viral diseases, as well as an attractive alternative for
controlling bacterial and fungal phytopathogens. While there are specific and well-defined
treatments for bacterial and fungal infections, they address one issue but jeopardize the
effectiveness and efficiency of medications used in the healthcare and veterinary sectors.

6. Conclusions
This review highlights the significant antimicrobial potential of coffee and its by-
products, attributed primarily to bioactive compounds such as chlorogenic and caffeic
acids. These compounds have been shown to be effective against a range of bacterial, fungal,
and viral pathogens, offering promising solutions for combating antimicrobial resistance
in healthcare and agriculture. In agriculture, coffee-derived compounds could serve as
Microorganisms 2025, 13, 215 16 of 20

eco-friendly alternatives for controlling crop diseases, addressing the rising resistance to
antibiotics and fungicides. The growing challenge of microbial resistance underlines the
urgency of exploring natural sources such as coffee for the development of new antimicro-
bial agents. The reuse of coffee residues aligns with global efforts to enhance sustainability
and reduce waste, supporting a circular economy. The valorization of residues generated
during coffee processing, such as pulp, mucilage, husk, and spent grounds, presents a
sustainable alternative for mitigating environmental pollution while harnessing their bi-
ological activity for practical applications. Future research should focus on optimizing
extraction techniques and expanding the applications of these compounds across diverse
sectors, particularly in agriculture, where the use of eco-friendly alternatives is increasingly
critical. We believe that coffee and its by-products represent an invaluable resource for
advancing antimicrobial strategies, fostering sustainability, and promoting environmental
stewardship. Their integration into healthcare and agricultural practices holds innovative
potential, meriting continued investigation and development.

Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/microorganisms13020215/s1, Figure S1: Molecular structure of
hydroxybenzoic acids on coffee: (a) gallic acid, (b) syringic acid; Figure S2: Molecular structure of
hydroxycinnamic acids on coffee: (a) chlorogenic acid, (b) caffeic acid; Figure S3: Molecular structure
of flavonoids on coffee: (a) catechin, (b) que rcetin; Figure S4: Molecular structure of alkaloids on
coffee: (a) caffeine, (b) trigonelline; Figure S5: Molecular structure of diterpenes in coffee: (a) kahweol,
(b) cafestol.

Author Contributions: The author’s contributions were as follows: Conceived the idea, K.C. and
N.G.-M.; conducted the literature search and screening, R.C.-D., N.G.-M., and K.C.; drafted the
manuscript, R.C.-D., N.P.S.-B., N.G.-M., and K.C. All authors have read and agreed to the published
version of the manuscript.

Funding: The authors are grateful to the Departamento de Investigaciones Científicas y Tec-
nológicas de la Universidad de Sonora (DICTUS) for providing financial support for this research
(USO313008746 and USO313009127). Rosa Castro-Díaz thanks the Consejo Nacional de Ciencia y
Tecnología (CONAHCyT) for the scholarship received (CVU1301181).

Institutional Review Board Statement: Not applicable.

Informed Consent Statement: Not applicable.

Data Availability Statement: The original contributions presented in the study are included in the
article/Supplementary Materials, further inquiries can be directed to the corresponding authors.

Conflicts of Interest: The authors declare no conflicts of interest.

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