TRPLSC 1905 No.

of Pages 3

Trends in Plant Science

Forum
Promoting Model
Systems of Microbiota–
Medicinal Plant
Interactions
1,2,
Valentina Maggini, *
2 2 of its host [2]. Results allow the establish-
Alessio Mengoni, Patrizia Bogani,
Fabio Firenzuoli,1 and
Renato Fani2,*
The role of the interaction(s) be- fied model systems could enable these
tween medicinal plants (MPs) goals.
and their endophytes (bacterial
microbiome) in the production of
bioactive compounds (BCs) with
therapeutic properties is emerg-
ing. Here, we propose Echinacea
purpurea (L.) Moench as a new
model to reveal the intimate
crosstalk between MPs and bac-
terial endophytes, aiming to dis-
cover (new) BCs.
Echinacea purpurea: A Model for
from Thymus vulgaris); and/or the produc- However, there is a general lack of data
tion of anthraquinone rather than polysac- addressing the importance of endophytes
charides in Aloe vera; toxic substances on the growth, health, and therapeutic
could also be reduced or removed. In properties of MPs. Recently, Salvia
fact, some crops have been studied in de- miltiorrhiza was recommended as a possi-
tail as model systems to define their micro- ble prime model system to study how
biota and its role(s) in enhancing the growth its microbiota could affect the host metab-
olome [1]; in addition, the secondary
ment and characterization of microbial cul- metabolism of its seed microbiota has
ture collections to elucidate plant–microbe been functionally related to gene activities
interactions for a modern and sustainable in the plant genome [4]. Nevertheless, to
agriculture [3]. All these strategies could the best of our knowledge, in vitro models
also increase MP productivity, and simpli- of S. miltiorrhiza, grown and manipulated
under laboratory conditions with its micro-
biota, are still lacking. Such in vitro models
Box 1. Echinacea purpurea as an Available and Valuable Model System
Here, we advocate Echinacea purpurea as an available and valuable model system and highlight comparative
features of E. purpurea and Salvia miltiorrhiza useful for establishing model systems (Table I). Cultivable bacterial
strains have been isolated and characterized from E. purpurea stems, leaves, and roots, demonstrating that
these different plant compartments harbor different bacterial communities ([6] and references therein). The
presence of distinct bacterial microbiota in plant compartments could account for the different phytochemical
compositions characterizing these plant organs. To test this hypothesis, the role of the interaction(s) between
E. purpurea and its microbiota were investigated in the production of alkamides, phenylpropanoid, and volatile
organic compounds (VOCs). An infection model was established of axenic in vitro E. purpurea plants inoculated
with a pool of bacterial strains isolated from E. purpurea stems and leaves [5,10,11] and roots [10]. The results
revealed that secondary metabolite levels between control (not infected) and infected plants were different, sug-
gesting that the bacterial infection was able to modulate their biosynthesis. Moreover, the expression levels of a
gene involved in the metabolic pathway of the alkamide [valine decarboxylase (VDC)] was higher in the infected
E. purpurea tissues than in the control tissues [5].

Medicinal Plant–Microbiota Table I. Comparison of Echinacea purpurea and Salvia miltiorrhiza as Proposed MP Models
Interactions Feature Echinacea purpurea Refs Salvia miltiorrhiza Refs
Phytotherapy exploits the biological proper- In vitro plant–microbiota model Yes [5] No –
ties of phytocomplexes, extracted from Plant-cultivable microbiota Yes [6] No –
MPs following evidence produced by clini- Plant microbiome No – No –
cal research. The use of these preparations
Medicinal compound quantitative assay Yes [13] Yes [1]
has two main problems: the low concentra-
Genome sequence No – Yes [1]
tion of active substances both in the plants
and in the obtained preparations, and the Transcriptome Yes [14] Yes [1]

presence of unwanted substances. Im- Metabolome Yes [14] Yes [1]

provements in secondary metabolite pro- High market value Yes [8] No [8]
files could be obtained by investigating the Number of clinical trialsa 11/26b – 1/40c –
interaction(s) of the MP with its microbiota EMA clinical statement Yes – No –
[1]. The implications of such studies could Number of PubMed articles d
16/460 – 20/2800 –
be important for clinical phytotherapy. For
a
example, plant biosynthetic paths could be Searched on ClinicalTrial.gov on 26 November, 2019.
b
Eleven studies are based on E. purpurea preparations; one study is on a product containing E. purpurea plus
manipulated towards the overproduction E. angustifolia and two studies are on Echinacea products (with no species specified); the remaining trails are
of one or a few metabolites that the plant based on herbal products containing E. purpurea and other plants.
c
usually synthesizes in small quantities Almost all clinical trials are based on Chinese herbal formulations also containing S. miltiorrhiza; only one
study is on S. miltiorrhiza extract alone.
(e.g., curcuminoids in Curcuma longa); d
Number of PubMed articles on plant (E. purpurea or S. miltiorrhiza)–microbiota interactions out of the total
the synthesis of different essential oil article number for each plant (search strategy on PubMed: ‘plant name’ AND (microbiota OR microbiome OR
chemotypes (e.g., linalool and thymol endophyte*).

Trends in Plant Science, Month 2019, Vol. xx, No. xx 1

Trends in Plant Science

are essential if we are to elucidate the role the microbiome structure of E. purpurea is of E. purpurea alone (see Table I in Box 1).
of endophytes in the modulation of plant lacking, efforts are underway to sequence Finally, Echinacea spp. are an important
biosynthetic pathways. its genome fully, and the results are ex- economic commodity, with their global mar-
pected shortlyi. Moreover, the short-term ket value estimated to be US$50.7 million
Here, we advocate Echinacea purpurea use of E. purpurea-based medicines as a [8], which will be relevant to enable its suc-
as an alternative, available, and valuable traditional common cold treatment [7] has cessful translation from the laboratory to
[5] model system (Box 1) and present been approved by the European Medicines the clinic.
a comparative study of its advantages Agency (EMA)ii, particularly in terms of its
and disadvantages compared with suitable efficacy and safety profiles. Con- Concluding Remarks
S. miltiorrhiza (see Table I in Box 1). versely, S. miltiorrhiza is used in many clinical E. purpurea is a highly relevant medicinal
E. purpurea represents a suitable model studies as a traditional Chinese medicine, plant with a previously characterized chem-
system because of the thorough charac- which often comprise numerous herbs. In ical profile that contains well-established
terization of its microbiota ([6] and refer- fact, only one clinical trial (among 40 clinical therapeutic constituents and promising
ences therein) and the presence of a well- trials that involved multiple species in addi- new molecules for future study [9]. It
established in vitro model of the role of tion to S. miltiorrhiza on ClinicalTrial.gov) is also has a major role in studies investigat-
plant–microbiota interactions in the modu- investigating an extract containing exclu- ing the role of the plant microbiota in
lation of its secondary metabolite profile sively S. miltiorrhiza, while there are several the synthesis of BCs to determine the
[5], both of which are currently lacking for studies (11 out of 26 trials involving E. therapeutic properties of this plant. The
S. miltiorrhiza. Although characterization of purpurea) evaluating the efficacy and safety finding that different E. purpurea compart-
ments (roots, stems, and leaves) harbor
different bacterial communities paved the
way to establishing an in vitro model
(Box 1). Experiments performed with this
model demonstrated for the first time
that the plant–microbiota interaction could
influence the secondary metabolism of the
plant, affecting the (therapeutic) properties
of the plant [5,10,11]. Therefore, our
existing model based on E. purpurea can
be considered an excellent emerging
model system for medicinal plant–bacterial
interaction studies on the production of
BCs (Figure 1).

We are aware that a model system

needs to satisfy several criteria, such as
high economic value, ease of culture,
short seed germination and seedling
development time, and standardized
laboratory methods [12]. E. purpurea is
a commonly sold medicinal plant with a
high commercial value and it can be
grown in vitro relatively quickly (i.e.,
Trends in Plant Science seed germination of 6–7 days and seed-
Figure 1. Echinacea Model to Connect Fundamental and Applied Research on Medicinal Plants ling development of 5–6 weeks) with
(MPs). Both plant genotype and environmental factors (biotic and abiotic) can drive the development of the standard methods [5].
plant phenotype. Plant–microbiota interactions (at the genetic and biochemical levels) modulate the production
of secondary metabolites and the formation of new bioactive molecules, thus influencing the therapeutic
properties of the plant. Hence, fundamental research will pave the way to applied research that will enable the Thus, as recently highlighted elsewhere
use of this plant model as a producer (factory) of new ‘green’ (from plant) drugs. Figure created using [3], E. purpurea could be the ‘Arabidopsis’
BioRender (https://biorender.com/). for the future study of key MP species.

2 Trends in Plant Science, Month 2019, Vol. xx, No. xx

Trends in Plant Science
Acknowledgments
This work was supported by the Tuscany Region (Italy;
Resolution no. 1224/2016 ‘Medicine Complementari’)
and by Fondazione Cassa di Risparmio di Firenze
(project #2016.0936). The funding sources had no
involvement in any part of the study.
Resources
i
www.ncbi.nlm.nih.gov/bioproject/565869
ii
www.ema.europa.eu/en/medicines/herbal/
echinaceae-purpureae-herba
1
Research and Innovation Center in Phytotherapy and
Integrated Medicine, Careggi, University Hospital, Florence, Italy
2
Department of Biology, University of Florence, Florence, Italy
*Correspondence:
valentina.maggini@unifi.it (V. Maggini) and
renato.fani@unifi.it (R. Fani).
https://doi.org/10.1016/j.tplants.2019.12.013
© 2019 Elsevier Ltd. All rights reserved.
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