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Original article
Metabolic and microbial modulation of phenolic compounds from
raspberry leaf extract under in vitro digestion and fermentation
Jing Yang,
1,2
*
†
Yuxin Hao,
1†
Nana Li,
1
Chunyu Wang
1
& Yongping Liu
1
1 School of Chemical Engineering and Technology, North University of China, Taiyuan Shanxi, 030051, China
2 Dezhou Graduate School, North University of China, Dezhou Shandong, 253034, China
(Received 4 January 2021; Accepted in revised form 27 April 2021)
Summary Raspberry leaves, by-products in raspberry production, are also a rich source of bioactive phytochemicals.
In this study, the changes of phenolic compounds in raspberries leaf extract (RLE) under in vitro diges-
tion and colonic fermentation were further studied by HPLC-MS analysis and 16S rRNA. The results
showed that the phenolic compounds in RLE were relatively stable during in vitro gastric digestion; how-
ever, in the subsequent intestinal digestion and colonic fermentation, their content decreased sharply. A
large amount of hydroxyphenylpropionic acid, hydroxyphenylacetic acid and urolithins were produced
under the action of gut microbiota. Moreover, compared with corresponding control, RLE significantly
reduced the ratio of Firmicutes/Bacteroidetes in all volunteers, increased the relative abundances of some
beneficial bacteria, Enterococcus,Prevotella, and decreased the relative abundances of potential pathogens,
Clostridium and Faecalibacterium. These findings suggest that RLE during in vitro digestion and fermenta-
tion has positive effects on gut microbiota and potential value of maintaining intestinal health.
Keywords Colonic fermentation, gut microbiota, Rubus idaeus, urolithins.
Introduction
Raspberry is a Rubus plant in Rosaceae, also known
as Fu Pen Zi in China. Compared with raspberry fruit
with high nutritional value, raspberry leaf is also a rich
source of bioactive phenolic compounds which have
multi-functions, including inhibition of oxidation,
inflammation and cancer (Anastasia-Varvara & Fotini,
2016; Yu et al., 2019). A large number of raspberry
leaves are by-products of raspberry production. In our
previous study, the total phenolic contents (TPCs) by
colorimetry in raspberry leave extract (RLE) was 50%,
and the main polyphenols of RLE are free ellagic acid,
ellagitannin and quercetin-3-glucuronide (Q3G) (Yang
et al., 2019). Moreover, the TPCs of raspberry leaves
and fruits ranked 9
th
and 26
th
, respectively, in 54 plant
materials (Chen et al., 2020). Furthermore, another
study on mice fed RLE (100 mg day
1
kg
1
) for two
weeks suggested that RLE not only inhibited the
weight gain of mice, but also prolonged swimming
exhaustion time (Yang et al., 2020b). In Australia,
leaves are used to treat diarrhoea, while fruits are used
for prevention of constipation. However, despite the
long-term and in-depth research of pharmacologists in
the world, the efficacy of raspberry fruits, leaves and
roots is always between medicinal and/or edible. It
may be used as a ‘prodrug’ for target tissues or to pro-
mote health by improving intestinal flora, indicating
long-term and low toxicity (Yu et al., 2019; Sheng
et al., 2020).
It has been estimated that the whole colonising micro-
biota is made up of approximately 10
14
cells, and the
collective bacterial genome is 100 times larger than the
entire human genome (Sender et al., 2016). The gut
microbiota, a complex microbial community, changes
the physiological function of the host through the pro-
duction of signal molecules and neurotransmitters,
which helps to regulate the host energy metabolism, sys-
tematic immune response and maintain the stability of
the homeostasis (Nicholson et al., 2012). Part of the
dietary polyphenols (e.g. ellagitannin) that are not
digested and absorbed in small intestine will be metabo-
lised by gut microbiota in colon into a series of bioavail-
able metabolites, such as urolithins (Kang et al., 2016).
Urolithin A has reduced fat synthesis and triglyceride
accumulation in adipocytes and hepatocytes and
increased fat oxidation dependent on AMPK metabolic
pathway; however, iso-urolithin A and urolithin B have
no such activities (Kang et al., 2016a; Kang et al.,
*Correspondent: E-mail: yangjing5152@163.com
†
These authors are co-first authors.
International Journal of Food Science and Technology 2021, 56, 5168–5177
doi:10.1111/ijfs.15083
©2021 Institute of Food Science and Technology
5168