nutrients

Review
Fermented Foods: Definitions and Characteristics,
Impact on the Gut Microbiota and Effects on
Gastrointestinal Health and Disease
Eirini Dimidi † , Selina Rose Cox † , Megan Rossi and Kevin Whelan *
King’s College London, Department of Nutritional Sciences, London SE1 9NH, UK
* Correspondence: kevin.whelan@kcl.ac.uk
† The two authors contributed equally.




Received: 9 July 2019; Accepted: 2 August 2019; Published: 5 August 2019


Abstract: Fermented foods are defined as foods or beverages produced through controlled microbial
growth, and the conversion of food components through enzymatic action. In recent years, fermented
foods have undergone a surge in popularity, mainly due to their proposed health benefits. The aim
of this review is to define and characterise common fermented foods (kefir, kombucha, sauerkraut,
tempeh, natto, miso, kimchi, sourdough bread), their mechanisms of action (including impact on the
microbiota), and the evidence for effects on gastrointestinal health and disease in humans. Putative
mechanisms for the impact of fermented foods on health include the potential probiotic effect of their
constituent microorganisms, the fermentation-derived production of bioactive peptides, biogenic
amines, and conversion of phenolic compounds to biologically active compounds, as well as the
reduction of anti-nutrients. Fermented foods that have been tested in at least one randomised
controlled trial (RCT) for their gastrointestinal effects were kefir, sauerkraut, natto, and sourdough
bread. Despite extensive in vitro studies, there are no RCTs investigating the impact of kombucha,
miso, kimchi or tempeh in gastrointestinal health. The most widely investigated fermented food is
kefir, with evidence from at least one RCT suggesting beneficial effects in both lactose malabsorption
and Helicobacter pylori eradication. In summary, there is very limited clinical evidence for the
effectiveness of most fermented foods in gastrointestinal health and disease. Given the convincing
in vitro findings, clinical high-quality trials investigating the health benefits of fermented foods
are warranted.

Keywords: kefir; kombucha; sauerkraut; miso; natto; tempeh; soy; kimchi; sourdough; fermented food

1. Introduction
Fermented foods are defined as “foods or beverages produced through controlled microbial
growth, and the conversion of food components through enzymatic action” [1]. Many foods have
historically undergone fermentation, including meat and fish, dairy, vegetables, soybeans, other
legumes, cereals and fruits. There are several variables in the fermentation process including the
microorganisms, the nutritional ingredients and the environmental conditions, giving rise to thousands
of different variations of fermented foods. Historically, food fermentation was performed as a
method of preservation, as the generation of antimicrobial metabolites (e.g., organic acids, ethanol and
bacteriocins) reduces the risk of contamination with pathogenic microorganisms. Fermentation is also
used to enhance the organoleptic properties (e.g., taste and texture), with some foods, such as olives,
being inedible without fermentation that removes bitter phenolic compounds.
There are two main methods through which foods are fermented. Firstly, foods can be fermented
naturally, often referred to as “wild ferments” or “spontaneous ferments”, whereby the microorganisms

Nutrients 2019, 11, 1806; doi:10.3390/nu11081806 www.mdpi.com/journal/nutrients

Nutrients 2019, 11, 1806 2 of 26

are present naturally in the raw food or processing environment, for example sauerkraut, kimchi, and
certain fermented soy products. Secondly, foods can be fermented via the addition of starter cultures,
known as “culture-dependent ferments”, for example kefir, kombucha and natto [2]. One method of
performing a culture-dependent ferment is “backslopping”, in which a small amount of a previously
fermented batch is added to the raw food, for example sourdough bread [1]. Starters used to initiate
fermentation can be either natural (e.g., backslopping), or selected commercial starters to standardize
the organoleptic characteristics of the final product [3].
Fermented foods hold a firm place in cuisine from almost every culture in the world. In the West,
there has been a surge in popularity of fermented foods in recent years, major reasons including the
proposed health benefits of fermented foods and surging interest in gastrointestinal health. There are
several mechanisms through which fermented foods may exert beneficial effects in health and disease.
Firstly, they contain potentially probiotic microorganisms, such as lactic acid bacteria [1]. In general,
most fermented products have been found to contain at least 106 microbial cells per gram, with
concentrations varying depending on several variables such as the product’s region, age and time
at which the products are analysed/consumed [2]. The surrounding food matrix appears to play an
important role in the survival of probiotic strains via its buffering and protective effect against gut
conditions (e.g., low pH, bile acids) [4]. Indeed, a number of studies have shown that microorganisms
from fermented foods can reach the gastrointestinal tract, this is likely to differ across products, and
their presence in the gut appears to be transient [5]. Nonetheless, these microorganisms may still
have the potential to exert a physiological benefit in the gut, through competition with pathogenic
bacteria and the production of immune-regulatory and neurogenic fermentation by-products [6].
Secondly, fermentation-derived metabolites may exert health benefits. For example, lactic acid
bacteria (relevant to both dairy and non-dairy fermented foods) generate bioactive peptides and
polyamines with potential effects on cardiovascular, immune and metabolic health [7]. Thirdly,
fermentation may convert certain compounds to biologically active metabolites. For example, lactic
acid bacteria can convert phenolic compounds (such as flavonoids) to biologically active metabolites [8].
Fourthly, food components found in fermented foods, such as prebiotics and vitamins, may also
exert health benefits [1,9]. Lastly, fermentation can reduce toxins and anti-nutrients, for example,
fermentation of soybeans may reduce phytic acid concentrations [10], and sourdough fermentation can
reduce the content of fermentable carbohydrates (e.g., fermentable oligosaccharides, disaccharides,
monosaccharides and polyols, FODMAPs), which may increase the tolerance of these products in
patients with functional bowel disorders such as irritable bowel syndrome [11].
This review aims to define and characterise common fermented foods, their mechanisms of action
(including impact on the microbiota), and the evidence for effects on gastrointestinal health and disease
in humans. The evidence for the effects of yoghurt and cheese on human health has been extensively
reviewed elsewhere [12,13] and, therefore, this review will focus specifically on kefir and the major
non-dairy fermented foods: kombucha; sauerkraut; tempeh; natto; miso; kimchi; and sourdough bread
(Table 1).
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Table 1. Description and microbial content of common fermented foods.

Name Description Region of Origin Source of Microorganisms Microorganisms Identified in Final Product *
Lactobacillus kefiri, Lactobacillus paracasei, Lactobacillus parabuchneri, Lactobacillus
Kefir Fermented milk beverage Caucasus Starter culture casei, Lactobacillus lactis, Lactococcus lactis, Acetobacter lovaniensis, Kluyveromyces
Lactis, Saccharomyces cerevisiae
Komagataeibacter xylinus, Saccharomyces cerevisiae, Zygosaccharomyces bailii.
Brettanomyces bruxellensis, Acetobacter pasteurianus, Acetobacter aceti, Saccharomyces
Kombucha Fermented tea beverage China Starter culture
cerevisiae, Zygosaccharomyces bailii, Brettanomyces bruxellensis, Acetobacter xylinum,
Zygosaccharomyces spp., Acetobacter, Gluconacetobacter
Lactobacillus sakei, L. plantarum, Candidatus accumulibacter phosphatis, Thermatoga
spp., Pseudomonas rhizosphaerae, L. hokkaidonensis, L. rhamnosus, Leuconostoc
carnosum, Clostridium saccharobutyrilicum, Rahnella aquatillis, Citrobacter freundii,
Sauerkraut Fermented cabbage China Spontaneous Enterobacter cloacae, Bifidobacterium dentium, Enterococcus faecalis, Lactobacillus
casei, Lactobacillus delbrueckii, Staphylococcus epidermidis, Lactobacillus curvatus,
Lactobacillus brevis, Weissella confusa, Lactococcus lactis, Enterobacteriaceae,
Leuconostoc spp., Yarrowia brassicae
Enterococcus faecium, Rhizopus oryzae, Rhizopus oligoporus, Mucor indicus, Mucor
circinelloides, Geotrichum candidum, Aureobasidium pullulans, Alternaria alternata,
Cladosporium oxysporum, Trichosporon beigelii, Clavispora lusitaniae, Candida maltosa,
Fermented boiled and dehulled Starter culture
Tempeh Indonesia Candida intermedia, Yarrowia lipolytica, Lodderomyces elongisporus, Rhodotorula
soybeans (Rhizopus oligoporus)
mucilaginosa, Candida sake, Hansenula fabiani, Candida tropicalis, Candida
parapsilosis, Pichia membranefaciens, Rhodotorula rubra, Candida rugosa, Candida
curvata, Hansenula anomola
Starter culture
Natto Fermented soybean Japan Data not available
(Bacillus subtilis natto)
Starter culture Bacillus subtilis, Bacillus amyloliquefaciens, Staphylococcus gallinarum, Staphylococcus
Miso Fermented soybean paste Japan
(Aspergillus oryzae) kloosii, Lactococcus sp. GM005
Leuconostoc gasicomitatum, Leuconostoc gelidum, Leuconostoc mesenteroides, Weissella
Spontaneous, koreensis, Weissella confuse, Lactobacillus sakei, Lactobacillus plantarum, Lactobacillus
Kimchi Fermented vegetable dish Korea
Addedcommercially curvatus, Trichosporon domesticum, Trichosporon loubieri, Saccharomyces unisporus,
Pichia kluyveri
Bread made from longer
Sourdough bread Middle East and Europe Spontaneous or backslopping Data not available
ferment
* Data taken from [2,14–33].
Nutrients 2019, 11, 1806 4 of 26

2. Kefir
Traditional kefir, which originates from the Caucasus Mountains, is a fermented milk drink with a
creamy texture, sour taste and subtle effervescence. It is produced by adding a starter culture termed
“kefir grains” to milk. Kefir grains consist of symbiotic lactose-fermenting yeasts (e.g., Kluyveromyces
marxianus) and non-lactose fermenting yeasts (e.g., Saccharomyces cerevisiae, Saccharomyces unisporus), as
well as lactic and acetic acid producing bacteria, housed within a polysaccharide and protein matrix
called kefiran [34]. Lactic acids, flavour-generating components (e.g., acetaldehyde), ethanol and
carbon dioxide are all by-products of fermentation and contribute to the organoleptic properties of
kefir [35]. A dairy-free version of kefir also exists, called water kefir, which is a fermented beverage
made of water, sugar and water kefir grains, which contains bacteria and yeasts, albeit different to
the traditional kefir starter cultures. There is very limited evidence on water kefir and, therefore, this
section focuses on traditional kefir only.
A wide range of microbial species have been identified in kefir grains, commonly including
Lactobacillus brevis, L. paracasei, L. helveticus, L. kefiranofaciens, L. plantarum, L. kefiri, Lactococcus
lactis, Streprotcoccus thermophiles, Acetobacter lovaniensis, Acetobacter orientalis, Saccharomyces cerevisiae,
S. unisporus, Candida Kefyr, Kluyveromyces marxianus and Leuconostoc mesenteroides [14,36,37]. Following
fermentation, the microbial composition of kefir may change. For example, although not a predominant
Lactobacillus species in the kefir grain starter culture, L. kefiri can represent 80% of all Lactobacillus
species in the final fermented beverage [14,36]. The Food and Agriculture Organisation (FAO) and the
World Health Organisation (WHO) suggest that kefir grains should contain a minimum 107 colony
forming units (CFU)/g micoorganisms and the final product should contain at least 104 CFU/g of
yeast [38].
Several in vitro studies have investigated kefir’s antimicrobial activity, which is attributed to
competition with pathogens for available nutrients, as well as the production of organic acids,
bacteriocins, carbon dioxide, hydrogen peroxide, ethanol and diacetyl [39]. In vitro studies have shown
that kefir exhibits antimicrobial activity against Candida albicans, Salmonella typhi, Salmonella enterica,
Shigella sonnei, Escherichia coli, Bacillus subtilis, Enterococcus faecalis and Staphylococcus aureus [40,41].
Fermentation-derived bioactive peptides produced from casein have been shown to stimulate the
immune system in animal models [42], while kefiran reduced ovalbumin-induced cytokine production
in a murine asthma model [43]. In vitro and animal studies have also suggested potential anti-oxidative,
anti-hypertensive, anti-carcinogenic and cholesterol-and glucose-lowering effects of kefir [44–49].
The impact of kefir and its constituent microorganisms on the gut microbiota has been investigated
in several in vitro, animal and human studies. Although not yet confirmed in vivo, several strains
isolated from kefir have been shown to adhere to human enterocyte-like Caco-2 cells, indicating
a potential ability to colonise the human gut [50]. Kefir, or its constituent strains, have also been
shown to have a considerable impact on the gut microbiota population with increases in Lactobacillus,
Lactococcus and Bifidobacterium concentrations, and reductions in Proteobacteria and Enterobacteriaceae
concentrations, being demonstrated in numerous animal studies [51–53]. Furthermore, one study
found higher concentrations of Firmicutes, Bacteroidetes and Prevotella, as well as a higher stool weight
and stool water, in mice administered Lactobacillus kefiranofaciens (but not kefir per se), a common strain
found in kefir grains, compared to control [52]. In addition, a study showed that kefiran increased
stool weight and moisture in rats, in a dose-responsive manner, compared to control, suggesting a
potential beneficial effect in constipation [54]. The abundance of yeasts in the gastrointestinal tract
is also altered following kefir consumption; a study in a high-fat diet-induced obese mouse model
showed that those who ingested 0.2 mL kefir had significantly greater number of stool total yeasts and
Candida kefyr compared to control mice [55]. In humans, a study in 45 people with inflammatory bowel
disease showed that a kefir-specific strain, Lactobacillus kefiri, was identified in most participants’ faeces
4 weeks following 800 mL/day kefir consumption, and a significant increase in total stool Lactobacillus
abundance was found compared to control (no kefir) in patients with Crohn’s disease [56].
Nutrients 2019, 11, 1806 5 of 26

Kefir in Gastrointestinal Health and Disease

Several studies have been carried out in humans investigating the effect of kefir consumption on
gastrointestinal function and dysfunction. Kefir has been suggested to be well tolerated by people
with lactose malabsorption since it contains β-galactosidase expressing bacteria (e.g., Kluyveromyces
marxianus), which hydrolyses lactose, thus reducing lactose concentrations in the drink. Kefir contains
60% more β-galactosidase than plain yoghurt, while a 30% reduction in lactose content has been
shown in kefir compared with unfermented milk [57]. Despite reportedly greater β-galactosidase
concentrations in kefir than yoghurt, a small cross-over randomised controlled trial (RCT) in 15 people
with lactose malabsorption showed that although kefir produced a significantly lower breath hydrogen
concentration compared to milk, it was similar following kefir and plain yoghurt, suggesting that kefir
and plain yoghurt improved lactose digestion to a similar degree [57]. Kefir also led to a significantly
lower flatulence severity compared to milk, but no differences were seen for flatulence frequency,
abdominal pain and diarrhoea [57]. Overall, this study suggests kefir results in lower flatulence
severity than milk, and is as well tolerated as yoghurt, in people with lactose malabsorption.
Several non-randomised studies have also explored the impact of kefir in constipation [58–60]
(Table 2). A non-randomised cross-over study in 42 hospitalised patients with constipation and
mental and physical disabilities showed that 6 g of lyophilized kefir had no impact on laxative use,
stool consistency and stool volume compared to control powdered milk, however the number of
patients not requiring any laxatives was higher 12 weeks following the kefir intervention compared to
baseline (Table 2) [59]. Another small non-randomised, uncontrolled trial in 20 people with functional
constipation showed that 500 mLs of kefir for 4 weeks significantly increased stool frequency, improved
bowel satisfaction score and reduced gut transit time compared to baseline [60]. Considering the
small sample and limitations in study design (difference in kefir form, no randomisation, uncontrolled,
limited use of validated procedures), further high-quality trials are required to establish the impact of
kefir on constipation.
In a RCT, kefir led to a significantly greater increase in stool Lactobacillus concentration and in
blood haemoglobin concentration in patients with Crohn’s disease (n = 10) compared to control (n = 20)
(Table 2); no change was shown however in ulcerative colitis (n = 15) [56].
Another double-blind RCT investigated the impact of 500 mL/day kefir, compared to 250 mL/day
milk, on Helicobacter pylori eradication rates in patients with dyspepsia and diagnosed H. pylori infection
who were taking a triple antibiotic therapy for 2 weeks [61]. The study found that the rate of H. pylori
eradication was significantly higher in the kefir group (78%) compared to the control group (50%;
p = 0.026) [61]. The occurrence of diarrhoea, abdominal pain and nausea were also significantly lower
in the kefir group compared to control, suggesting kefir may be beneficial adjunct therapy during
treatment for H. pylori infections (Table 2).
Another double-blind RCT in 125 children prescribed antibiotics for upper respiratory infections
examined the effect of 150 mL/day kefir for 14 days, compared to 150 mL/day heat-treated kefir, in
preventing antibiotic-associated diarrhoea [62]. This study showed that kefir with live microorganisms
did not improved the rates of antibiotic-associated diarrhoea compared to control (relative risk 0.82,
95% confidence interval (CI) 0.54–1.43), and no differences were found for any of the symptoms
assessed, including abdominal pain, loose stools, constipation and vomiting (Table 2) [62].
There are currently no RCTs investigating the effects of kefir in functional bowel disorders.
To conclude, there is evidence from RCTs demonstrating kefir may be beneficial for lactose
malabsorption, and H. pylori eradication. However, an important limitation of kefir studies is that each
batch may consist of different microorganisms. This may explain some of the heterogeneous findings.
Further high-quality RCTs are needed to establish the impact of kefir on the gut microbiota and its
impact on other gastrointestinal disorders, such as constipation.
Nutrients 2019, 11, 1806 6 of 26

Table 2. Summary of interventions studies investigating the impact of kefir in gastrointestinal health and disease.

Study Study Design Study Population Intervention Control Duration Gut Microbiota Other Findings
6 g/day
Non-randomised,
lyophilized kefir. 6 g/day powdered Only three of the 11 participants experienced “more
cross-over Constipation,
Ino et al., 2015 [58] 3 g/day lactose in milk 3 months Not reported frequent BM without laxative use”. Summary descriptive
controlled n = 11
last 40 day of (baby-formula) statistics not shown.
intervention
treatment period
No difference in laxative use between kefir and control
Non-randomised, Constipation groups (7.5 times/3 months vs 8.1 times/3 months; p = 0.35).
Maki et al., 2018 6 g/day of 6 g/day powdered 12 weeks each
cross-over (hospitalised), Not reported No difference in number of people who did not require
[59] lyophilized kefir milk period
intervention study n = 42 laxatives.
No difference in stool consistency/volume.
Increased stool frequency at follow-up compared to
baseline (median 2 BM/week vs 5 BM/week; p < 0.001).
Fewer people with hard stools at follow-up compared to
Non-randomised, Functional baseline (12/20 vs 6/20; p = 0.014).
Turan et al., 2014
uncontrolled constipation, 500 mL/day kefir - 4 weeks Not reported Improvement in bowel satisfaction scores (p = 0.001).
[60]
intervention study n = 20 Reduction in gut transit time in participants with slow gut
transit time at baseline (p = 0.013).
No change in straining or laxative use.
No major adverse events.
Higher H. pylori eradication rate in kefir vs control (78% vs
Dyspepsia and H. 50%; p = 0.026).
Bekar et al., 2011
Double-blind RCT pylori infection, 500 mL/day kefir 250 mL/day milk 2 weeks Not reported Lower occurrence of diarrhoea (relative risk RR = 0.48;
[61]
n = 85 p = 0.001), headache (RR=0.17; p = 0.008), nausea (RR = 0.47;
p = 0.029), and abdominal pain (RR = 0.38; p < 0.001).
Higher breath H2 AUC in milk compared with plain kefir
1) 508 mL/day (p = 0.001), plain yogurt (p = 0.001), or flavoured yogurt
3) 407 mL/day low
plain kefir (p = 0.005).
fat cow’s milk Acute 5-day study,
Lactose 2) 519 g/day Higher breath hydrogen AUC in flavoured kefir compared
Hertzler et al., 4) 378 g/day plain each treatment
Cross-over RCT malabsorption, raspberry Not reported to plain yogurt (p = 0.043) or plain kefir (p = 0.008).
2003 [57] yoghurt followed by an 8 h
n = 15 flavoured kefir No difference in breath hydrogen AUC between flavoured
(equivalent to 20 g breath H2 test
(equivalent to 20 g kefir and milk (p = 0.425) or flavoured yogurt (p = 0.331).
lactose)
lactose) No difference in flatulence severity and frequency,
diarrhoea and abdominal pain.
Nutrients 2019, 11, 1806 7 of 26

Table 2. Cont.

Study Study Design Study Population Intervention Control Duration Gut Microbiota Other Findings
Antibiotic-associated
Merenstein et al., 75 mL/day to 150 No difference in rates of diarrhoea (relative risk 0.82, 95% CI
Double-blind RCT diarrhoea, Heat-treated kefir 2 weeks -
2009 [62] mL/day kefir 0.54–1.43).
n = 125
UC: No difference
in change of UC patients:
Lactobacillus No difference in change of blood haemoglobin
Inflammatory Crohn’s: Higher concentration
Yilmaz et al., 2018 bowel disease, change in Crohn’s disease:
RCT 400 mL/day kefir No kefir 4 weeks
[56] n = 45 (15 UC, 10 Lactobacillus in Higher change in blood haemoglobin in the kefir group
Crohn’s disease) kefir compared to compared to control (0.08% vs −0.01%; p = 0.029)
control (3.4% log10 No difference in change of blood CRP between the kefir and
vs –0.6% log10 ; control group
p = 0.024).
AUC area under the curve; BM bowel movements; RCT randomized controlled trial; UC ulcerative colitis.
Nutrients 2019, 11, 1806 8 of 26

3. Kombucha
Kombucha is a fermented tea beverage reported to have originated in Northeast China in
around 220 BC and consumed extensively during the Qin Dynasty. Similar fermented tea beverages
subsequently became popular in Russia and Eastern Europe [63]. In modern societies, a range of
kombucha beverages are available commercially, although the microbial and metabolite composition
of these products along with methods of production are rarely reported [15].
Traditional kombucha is produced through aerobic fermentation of black tea (green tea may also
be used) and white sugar by a combination of bacteria and yeast, known as the symbiotic culture of
bacteria and yeast (SCOBY). The yeast convert sucrose to ethanol (in addition to organic acids and
carbon dioxide) which acetic acid bacteria convert to acetaldehyde and acetic acid [64]. The microbial
and metabolite composition of kombucha varies according to the exact composition of the SCOBY,
the type and concentration of tea and sugar [65,66], oxygen concentrations, fermentation time [67,68],
temperature [67,69] and storage duration [65]. The low pH of kombucha, owing mainly to the
production of high concentration of acetic acid, has been shown to prevent the growth of pathogenic
bacteria such as Helicobacter pylori, Escherichia coli, Salmonella typhimurium and Campylobacter jejuni [70].
Even at neutral pH and after thermal denaturation, kombucha was able to inhibit the growth of
pathogens in vitro, suggesting that compounds other than acetic acid exert antimicrobial effects [70].
The bacterial and fungal species constituting the SCOBY typically include acetic acid
bacteria (Acetobacter, Gluconobacter), lactic acid bacteria (Lactobacillus, Lactococcus) and yeasts
(Saccharomyces, Zygosaccharomyces) [15,63,71]. Studies utilising high-throughput sequencing analysis
have demonstrated that following fermentation, Candida and Zygosaccharomyces genera are the
predominant yeasts in kombucha [15,16], while Komagataeibacter, Lyngbya, Gluconobacter, Lactobacilli
and Bifidobacteria are the most abundant bacterial genera.
Kombucha has been shown to exert effects in animal studies on blood glycaemia [72],
oxidative stress [73], diabetes-induced weight loss [74], chemically-induced nephrotoxicity [75],
hypercholesterolaemia [72,76] and indomethacin-induced gastric ulceration [77]. Compounds
hypothesised to play a role in these beneficial effects include d-saccharic acid-1,4-lactone (DSL).
This is produced by Gluconobacter during fermentation [78,79], and in rats, inhibits oxidative stress
and diabetes-induced renal damage [80] and acetaminophen-induced hepatic injury [81]. Nonetheless,
there is no human data on DSL to confirm this proposed mechanism of action. Polyphenol and
flavonoid content of tea increases with fermentation [15]. Furthermore, in vitro superoxide radical
scavenging ability, reducing ability and total phenolic compound concentration increases during
kombucha fermentation [82].
Although kombucha is a rich source of acetic acid and lactic acid bacteria and yeasts [15], there are
no published studies exploring the effect of kombucha consumption on the gastrointestinal microbiota
composition or function in either animals or humans. Interestingly, kombucha has been shown to have
antimicrobial effects in vitro [83,84]. It is currently unknown whether the proposed physiological effects
of kombucha are mediated by the gastrointestinal microbiota or other direct immunological pathways.
Despite evidence of physiological effects of kombucha consumption in animals, the effects in
humans remain largely unknown. A recent systematic review [85] did not identify any RCTs of
kombucha on gastrointestinal disorders, including any of the functional bowel disorders.
To conclude, there are no studies of the effects of kombucha on gastrointestinal health and
microbiota in humans.

4. Sauerkraut
Sauerkraut is one of the most common forms of preserved cabbage originating in the 4th century
BC. Sauerkraut is eaten frequently in Germany, but also in other European and Asian countries
and the United States [86]. Sauerkraut is produced from a combination of shredded cabbage and
2.3%−3.0% salt, which is left to undergo spontaneous fermentation, generally involving Leuconostoc
Nutrients 2019, 11, 1806 9 of 26

spp., Lactobacillus spp., and Pediococcus spp. The low pH of the final product results in a preserved
cabbage [87].
Sauerkraut (homemade and shop-bought) has been shown, through culture-dependent techniques,
to contain Bifidobacterium dentium, Enterococcus faecalis, Lactobacillus casei, Lactobacillus delbrueckii,
Staphylococcus epidermidis, Lactobacillus sakei, Lactobacillus curvatus, Lactobacillus plantarum, Lactobacillus
brevis, Weissella confusa, Lactococcus lactis and Enterobacteriaceae [17,18,88]. Adding a starter culture
of Lactobacillus casei 11MZ-5-1 produced a sauerkraut containing predominantly Lactobacillus and
Lactococcus, compared to spontaneous sauerkraut which, along with Lactococcus and Lactobacillus, also
contained significant Enterobacter and Pseudomonas and was more variable in microbial composition [89].
Sauerkraut has also been shown to predominantly contain Leuconostoc and Lactobacillus spp. [18,19,90,91].
Certain Lactobacillus species isolated from sauerkraut demonstrate probiotic potential, with tolerance to
low pH, adherence to Caco-2 cells and antimicrobial activity against pathogens in vitro [92]. Lactobacillus
paracasei HD1.7, commonly found in sauerkraut, has been shown to produce a broad-spectrum
bacteriocin that may play a role in sauerkraut preservation [93].
Oral administration of sauerkraut juices in Wistar rats led to increased activity of glutathione
S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), key liver and kidney detoxifying
enzymes [94]. Certain lactic acid bacteria contained in sauerkraut generate conjugated linoleic acid [95],
for which there is evidence of anti-carcinogenic and anti-atherosclerotic activity in animals [96,97].
Furthermore, Lactobacillus plantarum P2 isolated from sauerkraut significantly induced TNF-α and IL-12
expression and prevented adhesion and invasion of Caco-2 cells by Salmonella enteritidis [98]. Sauerkraut
contains glucosinolate breakdown products including kaempferol, (a flavonoid) isothiocyanates,
indole-3-carbinol, goitrin, allyl cyanide and nitriles [99]. The relevance of such phytochemicals to
human health is unclear, however kaempferol has been shown to have radical scavenging activity, to
protect from oxidative damage and to attenuate cytokine-induced reactive oxygen species in vitro [100].
Isothiocyanates have been shown to have antimicrobial properties, preventing the growth of a range of
species, including E. coli, C. difficile, C. jejuni and C. perfringens [101].
Sauerkraut is one of the few fermented foods for which there is a clinical trial in functional bowel
disorders. A randomised double-blind trial compared the effects of sauerkraut containing viable lactic
acid bacteria (LAB) on gastrointestinal symptoms and microbiota in 58 patients with irritable bowel
syndrome (IBS) of any subtype diagnosed using Rome III criteria [18]. Patients were randomised to
consume 75 g/day pasteurised (control) or unpasteurised (intervention) sauerkraut containing LAB for
6 weeks. There was a significant reduction in IBS Severity Scoring System (IBS-SSS) score between
baseline and end of trial in both study groups, however there was no difference in symptoms between
the diet groups; 16S rRNA sequencing revealed no difference in microbiota composition between
study groups or between baseline and end of trial in either group (Table 3). This may suggest that
the perceived health benefit of sauerkraut is independent of the live microbes. A limitation of this
study is the per protocol analysis in that only patients who completed the study (n = 34) were included
in the analysis of the primary outcome. Furthermore, because there was no raw cabbage arm, it is
not possible to determine whether improvement in gastrointestinal symptoms was related to the
fermentation-derived products or the cabbage itself.
Another study in Chinese participants suggested larger amount of sauerkraut may in fact be
associated with poor health outcomes in gastrointestinal cancers. This case-control study found that
the highest compared to the lowest quintile of sauerkraut intake was associated with a greater risk
of laryngeal cancer (odds ratio (OR) 7.27) [102]. One possible mechanism may relate to the high salt
content of sauerkraut, although another case-control study of dietary risk factors for laryngeal cancer
in China showed no associations with salt-preserved vegetables [103]. Similarly, the high potassium
content of sauerkraut is thought to counter the hypertensive effects of added salt.
Nutrients 2019, 11, 1806 10 of 26

Table 3. Summary of interventions studies investigating the impact of sauerkraut, soy products and kimchi in gastrointestinal health and disease.

Fermented Study
Study Study Design Intervention Control Duration Gut Microbiota Other Findings
Food Population
Following natto-containing
200 mL miso soup:
Uncontrolled
Fujisawa et al., Healthy, soup containing Higher Bifidobacteria and Bacilli,
Natto/miso open-label - 2 weeks -
2006 [104] n=8 50 g Natto per Lower Enterobacteriaceae,
study
day Higher acetic acid and
propionic acid (all p < 0.05)
H. pylori not eradicated in any
participants (p = 0.944).
H. pylori Increased Lactobacillus
Kil et al, 2004 Non-randomised Lower stool pH (p = 0.0001),
Kimchi infection, 300 g of kimchi 60 g of kimchi 4 weeks (p = 0.0003) and Leuconostoc
[105] trial β-glucuronidase (p = 0.0065)
n=6 (p = 0.0004)
and β-glucosidase (p = 0.0001)
activity
Following Natto compared to
Infrequent 50 g/day Natto Following Natto compared to control:
Mitsui et al., bowel (Bacillus subtilis 50 g/day boiled control: Higher number of bowel
Natto Controlled trial 2 weeks
2006 [106] movements, K-2, 3.8 × 109 soybeans Increased ratio of stool movements. Higher number of
n = unknown CFU) Bifidobacteria:total bacteria days with bowel movements
Higher stool quantity
Lower IBS-SSS score following
75 g/day No significant effects of either both unpasteurised (p = 0.003)
Randomised, Irritable bowel 75 g/day
Nielsen et al., unpasteurised unpasteurised or pasteurised and pasteurised (p = 0.04)
Sauerkraut double-blind syndrome, pasteurised 6 weeks
2018 [18] sauerkraut sauerkraut on microbiota sauerkraut
controlled trial n = 58 sauerkraut
containing LAB composition No difference in change in
IBS-SSS between groups
LAB, lactic acid bacteria; IBS-SSS Irritable Bowel Syndrome Severity Scoring System.
Nutrients 2019, 11, 1806 11 of 26

Taking the limited evidence for sauerkraut into account, one trial indicates that both pasteurised
and unpasteurised sauerkraut reduced IBS severity, this effect does not appear to be mediated by
gastrointestinal microbiota. Further studies are required to elucidate the mechanisms of this effect on
gastrointestinal symptoms. There is little evidence for effects of sauerkraut on other health conditions.

5. Fermented Soy Products (Tempeh, Natto, Miso)

The first known fermented soy products originated in China and Japan, including fermented black
soybean and red fermented tofu [107]. There are many fermented soybean products from different
parts of Asia, including tempeh, natto, miso, sufu, douche, soy sauce and doenjang. This review will
focus on tempeh, natto and miso.

5.1. Tempeh
Tempeh is a traditional Indonesian food produced by fermenting boiled and dehulled soybeans
with a starter culture of Rhizopus oligoporus fungal species at room temperature for 35–37 hours [107,108].
This produces a soft white cake with a chewy texture and mushroom-like flavour. The microbial
composition of tempeh varies according to variations in production [109]. Tempeh contains lactic
acid bacteria [2,110], Enterococcus faecium [110], and Rhizopus filamentous fungi. Fermentation of
soybeans has been shown to reduce concentrations of protease inhibitors, phytic acid and phenols [10],
antinutritional factors that are high in raw soybeans, which may relate to phytases expressed by
Rhizopus species in tempeh [111].
In Sprague–Dawley rats, stool Bacteroidetes, Firmicutes, Clostridium leptum and Bacteroides
fragilis abundance increased following tempeh supplementation compared to rats fed non-fermented
soybeans [112]. Application of soybean and bean tempeh to human microbiota in an in vitro gut
simulator model increases Bifidobacterium, Lactobacillus, Escherichia coli and Enterococcus abundance [113].
In an open-label uncontrolled study of 10 healthy human volunteers, tempeh consumption led to
greater stool Akkermansia muciniphila abundance and immunoglobulin A concentrations, suggesting
that tempeh may influence gut microbiota in humans [114]. However, a larger, controlled study is
needed to establish the effects of tempeh on gastrointestinal microbiota composition.
Fermented soy products have been proposed to have beneficial effects on health,
including purported “anti-carcinogenic”, “anti-diabetic”, “antioxidant”, “anti-inflammatory” and
“anti-hyperlipidaemic” effects, although much of the existing evidence is limited to in vitro and animal
studies [107]. Tempeh has been associated in vitro with greater free-radical and superoxide scavenging
ability than unfermented soybeans [115], which may relate to changes in polyphenol content and
digestibility in soybeans following fermentation [116,117].
To date, there are no RCTs of the effects of tempeh consumption in humans. Proposed health
effects listed above require investigation in human trials.

5.2. Natto
Natto is a traditional Japanese fermented soybean, of which Itohiki-Natto is the most commonly
consumed [108]. Natto is produced through fermentation of cooked yellow soybeans with Bacillus
subtilis var. natto. This produces a viscous food with a distinct flavour and strong odour [118]. Natto
characteristics vary according to soybean steaming time, relative humidity, fermentation time and
temperature [108]. The fermentation of Natto produces a number of bioactive factors, including
nattokinase, bacillopeptidase F, vitamin K2 and dipicolinic acid [108]. Furthermore, the quantity of
the isoflavone genistein, with purported associations with metabolic and inflammatory disorders and
carcinogenesis [119], is greater in Natto compared to unfermented soy products [120]. A peptide with
antibacterial activities against Streptococcus pneumoniae and Bacillus subtilis has been isolated from
Natto [121], with potential clinical importance in treating S. pneumoniae infections, although this has
not been investigated in humans.
Nutrients 2019, 11, 1806 12 of 26

Nattokinase is an enzyme of the subtilisin family produced by Bacillus subtilis var. natto [122],
and can be isolated from Natto [123]. Nattokinase has direct in vitro [123] and in vivo [124]
fibrinolytic activity, in addition to increasing tissue plasminogen activator [125] and reducing
platelet aggregation [126]. Anti-thrombotic and anti-hypertensive activities of nattokinase have
been demonstrated in small RCTs in humans [127,128].
There is limited evidence on the effect of Natto on the human GI microbiota. Consumption of
Natto-containing miso soup for two weeks led to increased stool Bacilli and Bifidobacteria and decreased
Clostridia and Enterobacteriaceae in 8 healthy volunteers [104]. Furthermore, stool short-chain fatty
acids increased, and ammonia and sulphide declined. However, it is impossible to separate the
effect of the miso soup (also a fermented soy product) from possible effects of Natto. In individuals
with 3–5 bowel movements per week, consumption of 50 g/day Bacillus subtilis K-2 containing Natto
for two weeks resulted in greater stool frequency and proportion of stool Bifidobacteria compared to
consumption of 50 g/day of boiled beans [106], although only the abstract is available and no sample
size is provided.
To date, there is limited evidence from RCTs suggesting Natto might positively influence stool
frequency in patients with infrequent bowel motions and influences gastrointestinal microbiota.
However, these require confirmation in high quality trials.

5.3. Miso
Miso is a traditional Japanese paste of fermented soybean used to make miso soup. Miso is
produced by fermenting soybeans with ‘Koji’, produced from a mould Aspergillus oryzae, although
Saccharomyces cerevisiae and lactic acid bacteria may additionally be used. As with other fermented soy
foods, miso production varies greatly in terms of ingredients, temperature and fermentation time, salt
concentration and the strain of A. oryzae used.
A microbial analysis of miso at different time points following the start of fermentation revealed
Bacillus subtilis, Bacillus amyloliquefaciens, Staphylococcus gallinarum and Staphylococcus kloosii to be
present during fermentation, with only the Bacillus species remaining in the final product [129]. A range
of miso samples have also been shown to contain Lactococcus sp. GM005, which produces a bacteriocin
with strong antibacterial activity that inhibits the growth of a range of bacteria, including Bacillus
subtilis, Pediococcus acidilactici and Lactobacillus plantarum [130,131].
There is little evidence on the effect of miso intake on gastrointestinal disorders. One cross-sectional
study reported an inverse relationship between miso soup intake and subjective gastro-oesophageal
reflux disease, functional dyspepsia and reflux scores when adjusted for other dietary factors [132].
This association was hypothesised to relate to histidine, glutamate and aspartate found in miso soup,
although no animal or human studies have investigated this mechanism to date.
The high soy intakes in China and Japan have historically been hypothesised to contribute to the
relatively low rates colon and prostate cancers in these countries [133]. One proposed mechanism
to support this hypothesis is the high concentrations of isoflavones genistein and daidzein found in
soybeans [134]. Genistein is structurally similar to oestrogen and may influence breast cancer risk
through oestrogen receptor binding, which has been demonstrated in vitro [135,136]. Further in vitro
studies have demonstrated that genistein may exert effects on cancer risk through promoting cell-cycle
arrest [137] inducing apoptosis [138] and reducing cancer cell migration [139]. Genistein and daidzein
may be higher in fermented soybean products (miso and natto) compared to unfermented products
such as soy milk and tofu [120,140,141], as previously discussed. Numerous Japanese cohort studies
have investigated associations between miso intake and cancer risk. These studies are limited in the
assessment of dietary intake (food frequency questionnaires, often with limited intake responses) and
the presence of a multitude of possible confounding factors. With these methodological limitations
in mind, cohort studies have observed inverse associations between frequent miso soup intake and
stomach cancer risk in Japanese men [142]. In contrast, cohort and case-control studies have shown
positive correlations between frequent miso soup intake and single and multiple stomach cancers in
Nutrients 2019, 11, 1806 13 of 26

Japanese adults [143]. Furthermore, some cohort studies have shown no association between miso
soup intake and risk of various types of cancer [144,145].
There are currently no RCTs investigating the effects of miso in functional bowel disorders. There
is therefore limited evidence for the effects of miso on gastrointestinal conditions and microbiota.
There are several observational studies demonstrating associations between miso intake and the risk of
stomach cancer, however the strength and direction of these associations remains unclear.

6. Kimchi
Kimchi, which originates from Korea, is a term used for a group of salted and fermented vegetables.
It consists of Chinese cabbage and/or radishes, and various flavouring ingredients (e.g., chili, pepper,
garlic, onion, ginger), seasonings (e.g., salt, soybean sauce, sesame seed), and other additional foods
(e.g., carrot, apple, pear, shrimps) [20]. To produce kimchi, the cabbage is brined and drained, then
the rest of the seasonings, spices and food products are added and mixed with the cabbage, and
finally, fermentation takes place (134). The fermentation occurs spontaneously by the microorganisms
naturally found on the cabbage and foods included in the mixture, although starter cultures may be
used for commercial production of kimchi [20].
Prior to fermentation, the kimchi mix contains a variety of different bacterial species within the
Leuconostoc, Lactobacillus, Pseudomonas, Pantoea and Weissella genera [21] (Table 1). However,
once fermentation has started, the bacterial diversity decreases and the bacterial community is rapidly
dominated by the genus Leuconostoc within only three days of fermentation [21]. Within this
genus, Leuconostoc citreum is the most abundant species prior to fermentation, but it is present
in only a minor proportion after three days of fermentation, at which time point Leuconostoc
gasicomitatum and Leuconostoc gelidum become dominant [21]. As kimchi can comprise a variety of
ingredients, the microbial composition varies depending on the type and amount of the foods included.
For example, a higher Lactobacillus concertation has been found when kimchi contains a higher
garlic quantity [146], while the addition of red pepper powder leads to higher Weissella and lower
Leuconostoc and Lactobacillus proportions [147]. Several archaea (e.g., Halococcus, Natronococcus) and
yeast (e.g., Saccharomyces, Candida, Trichosporon) genera have also been identified in commercially
available kimchi [22] (Table 3). An animal study showed that kimchi consumption, which contained
Leuconostoc mesenteroides DRC 0211, may exhibit potential weight control properties in mice via
reducing hepatic mRNA expression of adipogenesis-related genes and inflammation-related monocyte
chemotactic protein-1 and interleukin-6 in epididymal fat tissue [148]. Reductions in serum total
cholesterol, triglycerides, low-density lipoprotein cholesterol levels and atherogenic index have
also being demonstrated in rats following consumption of kimchi fermented by Leuconostoc kimchi
GJ2 [149]. A human study demonstrated that consumption of kimchi fermented for 8 weeks led
to changes in expression of genes related to metabolic pathways and immunity [150]. In a mouse
colitis model, Lactobacillus paracasei LS2, a strain isolated from kimchi, decreased cytokine production,
myeloperoxidase activity, and the number of macrophages and neutrophils in the lamina propria
lymphocytes, suggesting a potential anti-inflammatory effect [151]. Anti-carcinogenic properties have
also been attributed to kimchi with an in vitro study demonstrating inhibition of gastric cancer cell
growth [152]. Notably, as kimchi comprises a variety of ingredients, its impact on the gut microbiota
and health is thought to result from a synergic effect of the microorganisms it contains, as well as
the nutrient content (e.g., phytochemicals, fibre, vitamins) of the foods used in the preparation. For
example, antimicrobial and antioxidant effects have also been attributed to food constituent of kimchi,
such as red pepper seeds and garlic [153,154].
Several studies have investigated the impact of kimchi on the gut microbiota. A study on
diet-induced obesity murine models showed that Lactobacillus plantarum HAC01, isolated from kimchi,
resulted in a higher Adlercreutzia and lower Bacteroides, Mucispirillum and Ruminococcus proportions
compared to control mice [155]. In humans, a non-randomised study of 6 people in South Korea
showed that consumption of 300 g/day kimchi for 4 weeks increased stool concentrations of Lactobacillus
Nutrients 2019, 11, 1806 14 of 26

and Leuconostoc, and decreased stool pH, compared to 60 g/day of kimchi [105]. Similar findings have
also been identified in several other non-randomised human studies [156,157]. In a RCT of fermented
compared to fresh (unfermented) kimchi in 24 women with obesity, women who were randomised
to receive 180 g/day fermented kimchi for 8 weeks showed a decrease in Blautia abundance and
increases in Prevotella and Bacteroides abundance compared to baseline, but both groups (fermented
and unfermented kimchi) experienced increases in Proteobacteria and Actinobacteria abundance [150].
Another RCT compared two different kimchi preparations made of different ingredients and quantities;
kimchi I contained baechu cabbage, radish, red pepper powder, green onion, garlic, ginger, anchovy
juice, and sugar, while kimchi II contained organic baechu cabbage, radish, red pepper powder, green
onion, garlic, ginger, sugar, mustard leaf, Chinese pepper, pear, Lentinus edodes juice and sea tangle juice,
mistletoe extract powder, and 106 CFU/g of Lactobacillus plantarum PNU [158]. Both kimchi groups
resulted in an increased abundance of short-chain fatty acid producing Faecalibacterium, Roseburia, and
Phascolactobacterium, and reduced Clostridium and Escherichia coli compared to baseline. Although no
direct comparisons between the two kimchi groups were made, kimchi I was shown to increase the
relative abundance of Actinobacteria and decrease that of Proteobacteria compared to baseline, whereas
kimchi II had the opposite effect suggesting that different types and quantities of ingredients in kimchi
may impact the microbiota differently [158].
With regards to the effects of kimchi on gastrointestinal health and disease, a very small study
attempted to investigate its impact on H. pylori eradication. Six people with H. pylori infection consumed
300 g (high dose) or 60 g (low dose) of kimchi for 4 weeks in a non-randomised trial [105]. H. pylori
infection, assessed via 13 C urea breath test, was not eradicated in any of the six participants at the end
of the intervention [105] (Table 2). Kimchi has also been investigated with regards to its association
with gastric cancer in epidemiological studies. A number of epidemiological studies have shown an
increased risk of gastric cancer in the Korean population with higher kimchi intake (OR 2.2, 95% CI
1.3–3.8), which has been suggested to be due to its nitrite, nitrate and salt content [159,160]. However, a
case control study of 136 patients diagnosed with gastric cancer and 136 healthy controls showed that
different types and preparations of kimchi were associated with different levels of gastric cancer risk;
for example, moderate baiechu kimchi (prepared with salted Chinese cabbage) intakes were associated
with a lower gastric cancer risk (OR 0.5, 95% CI 0.3–0.9), while moderate intakes of kkakduki (prepared
with salted radish) were associated with a higher gastric cancer risk (OR 2.0, 95% CI 1.03–3.8) [161].
These differences could potentially be attributed to the different food and nutrient composition and
preparation methods of the different types of kimchi.
There are currently no RCTs investigating the effects of kimchi in functional bowel disorders.
To conclude, there is preliminary evidence that kimchi may have an impact on the gut microbiota
composition. No evidence exists to date on the impact of kimchi on gastrointestinal health and disease,
while the association between kimchi consumption and gastric cancer risk warrants further research.

7. Sourdough Bread
The sourdough starter culture is produced through the fermentation of flour by lactic acid bacteria
and yeasts, that originate from the flour and surrounding environment. Making the sourdough starter
takes on average seven days and involves replenishing the microbes with fresh flour and water daily.
Once the starter is ready, a small portion is added to the sourdough base ingredients to initiate the
sourdough fermentation process—this method is commonly referred to as “backslopping” [24,160].
Unlike standard bread, which is produced through a rapid yeast-only fermentation process, the
symbiotic sourdough fermentation of both bacteria and yeast is thought to improve bread quality,
including texture, flavour, nutritional content and shelf-life, and replace additives [24]. During
fermentation, microbial and enzymatic-led conversions of cereal carbohydrates, proteins, lipids and
phenolic compounds occur [24,162]. The microorganisms’ and enzymes’ activity are interlinked; for
example, lactic acid bacteria result in a pH reduction, modulating the activity of cereal enzymes and
Nutrients 2019, 11, 1806 15 of 26

solubility of substrates (e.g., gluten), and in turn the enzymes can provide substrates to allow the
growth of microorganisms [24].
The microbial content of the sourdough starter depends on the traditional practices used and,
therefore, not only the taste and texture, but the nutritional profile of the final product can vary
considerably [25]. In general, several species within the Lactobacillus, Leuconostoc, Weissella, Pediococcus
and Streptococcus genera have been identified in sourdough starters [162]. Lactobacillus species are the
most prevalent, and Lactobacillus sanfransiscensis is a key bacterium isolated from most starters [25].
Saccharomyces cerevisiae is the most abundant yeast species, followed by Candida milleri, C. humilis,
Saccharomyces exiguous and Issatchenkia orientalis. Only limited data exist on the microbial composition
of sourdough bread, likely due to the impact of heat during baking, with only one study showing a
gene copy number of 7 to 10 log gene copies/gram of sourdough bread [163].
The mechanisms through which sourdough bread may confer health benefits is primarily
through the impact that the sourdough process has on the nutritional content of bread. For example,
the sourdough process can lower the bread’s content of non-digestible oligosaccharides fructans
and raffinose (types of FODMAPs), resulting in the bread being better tolerated by patients with
IBS [11,164]. This change in the carbohydrate content occurs due to the degradation of oligosaccharides
by the sourdough microorganisms, especially the yeasts Saccharomyces cerevisiae and Kluyveromyces
marxianus [165]. Sourdough and its constituent microorganisms have also been suggested to exhibit
anti-microbial, anti-hypertensive, and cholesterol lowering properties, however these are based on
in vitro studies examining the impact of sourdough-extracted bacteria, rather than of baked sourdough
bread [166–168].
The effect of sourdough bread on the gut microbiota has been assessed in vitro and in vivo.
The impact of sourdough wheat breads fermented for different lengths of time on the human gut
microbiota was assessed using in vitro batch cultures with stool samples from 3 patients with IBS and
3 healthy donors [169]. A significant increase in bifidobacteria was shown in the healthy control samples
after addition of sourdough bread fermented for 8 h compared to a non-fermented bread. Significant
decreases in δ-Proteobacteria and Gemmatimonadetes was shown after inoculation of sourdough
bread fermented for 8 hours in both patients with IBS and healthy donors, compared to baseline (prior
inoculation) [169]. In addition, sourdough bread that was fermented for 8 h resulted in significantly
lower gas production after 15 h of inoculation of IBS samples, compared to a non-fermented bread and
bread fermented with yeast for 16 h. The authors suggested this may indicate that this sourdough bread
was fermented more slowly by the gut microbiota [169]. In vivo, however, a randomised cross-over
study in 20 healthy adults showed no significant differences in stool microbiota composition when
consuming 145 g wholegrain wheat sourdough bread per day for 1 week, compared to 110 g white
wheat bread, with the microbiota remaining resilient throughout both bread interventions [170].

Sourdough Bread in Gastrointestinal Health and Disease

Several studies have examined the impact of sourdough bread in gastrointestinal function and
disorders. In a double-blind, cross-over RCT, 17 healthy adults were randomised to consume a
single meal of 2 sourdough croissants or 2 brewer’s yeast croissants, followed by magnetic resonance
imaging analysis of gastric emptying [171]. The total gastric volume was significantly reduced by
11% and hydrogen production by 30% following sourdough croissants compared to brewer’s yeast
croissants [171]. Abdominal discomfort, bloating and nausea were significantly milder, suggesting
sourdough croissants are better tolerated than brewer’s yeast croissants [171]. In addition, a very small
randomised cross-over trial of 7 participants reporting minor gastrointestinal symptoms showed a
significantly different exhaled breath volatile organic compound profile following sourdough rye bread
compared to wheat bread enriched with bioprocessed rye bran, however the impact on gastrointestinal
symptoms was not measured. This suggests that the potential health effects of sourdough rye bread
may indeed be mediated by the gut microbiota [172] (Table 4).
Nutrients 2019, 11, 1806 16 of 26

Table 4. Summary of interventions studies investigating the impact of sourdough bread in gastrointestinal health and disease.

Study Study Design Study Population Intervention Control Duration Other Findings
Significant interpersonal variability in glycaemic
145 g sourdough
Korem et al., 2017 Randomised Healthy, 110 g white wheat responses
wholegrain wheat 1 week
[170] crossover trial n = 20 bread Baseline microbiome could predict type of bread that
bread
results in lower glycaemic response in each participant
11% decrease in gastric volume AUC 3 h
post-consumption (p = 0.02)
Polese et al., 2018 Double-blind, Healthy, 2 sourdough 2 brewer’s yeast 30% lower hydrogen production during the 4 h
Single study day
[171] cross-over RCT n = 17 croissants croissants post-consumption (p = 0.03)
Milder abdominal discomfort (p = 0.002), bloating
(p = 0.001) and nausea (p = 0.004)
6–10 slices/day of Significant difference in exhaled breath volatile organic
Minor gastrointestinal 6–10 slices/day of
Raninen et al., 2017 Randomised wheat bread enriched compound profile between groups in fasting state
symptoms, sourdough 4 weeks
[172] cross-over trial with bioprocessed (p = 0.026). No difference was shown at 30, 60 and 120
n=8 wholegrain rye bread
(fermented) rye bran min after a standardised meal
Lower breath H2 in low FODMAP rye bread group
compared to traditional rye bread (median AUC 53
ppm vs 73; p = 0.01)
Milder flatulence (p = 0.04), abdominal cramps
Randomised, Irritable bowel 7–8 slices/day low 7–8 slices/day
Laatikainen et al., (p = 0.01), rumbling (p = 0.001) and total symptoms
double-blinded, syndrome, FODMAP sourdough traditional sourdough 4 weeks
2016 [11] (p = 0.02)
cross-over trial n = 87 rye bread rye bread
No difference in IBS-SSS (p = 0.40).
Lower weight in low FODMAP rye bread compared to
traditional rye bread (mean difference −0.5 kg, 95% CI
–0.9 –0.0; p = 0.03)
Irritable bowel 6 slices/day
6 slices/day No difference in gastrointestinal symptoms or markers
syndrome with yeast-fermented
Laatikainen et al., sourdough wheat of low-grade inflammation.
Double-blinded RCT subjective wheat wheat bread 7 days
2017 [164] bread (fermentation Worse symptoms of tiredness (p = 0.01), joint symptoms
intolerance, (fermentation time
time > 12 h) (p = 0.03) and “decreased alertness” (p = 0.003)
n = 26 approx. 2 h)
200 g/day baked
products with All patients had normal IgG and IgA-AGA and
Di Cagno et al., 2010 Non-randomised, Coeliac disease,
sourdough wheat None 60 days IgA-tTG antibodies values at the end of the
[173] uncontrolled study n=8
flour (10 g hydrolysed intervention period
gluten)
Sourdough wheat
No increase in INF-γ secretion
Mandile et al., 2017 Coeliac disease, bread (fermented Traditional wheat
RCT 3 days Mobilisation of INF-γ secreting cells in the blood
[174] n = 20 with lactobacilli and bread
following traditional wheat bread
yeast)
IBS-SSS Irritable Bowel Syndrome Severity Scoring System; RCT, randomized controlled trial.
Nutrients 2019, 11, 1806 17 of 26

The utility of adjusting the sourdough process to modify the nutritional content of bread was
shown in a double-blinded, cross-over RCT in 87 patients with IBS that examined the impact of a
sourdough rye bread prepared using a specific sourdough system that lowers the FODMAP content of
the bread versus a traditionally-made sourdough bread in gastrointestinal symptoms [11]. This study
showed a significantly lower breath hydrogen level, and significantly milder flatulence, abdominal
cramps, rumbling and total gastrointestinal symptoms following a 4-week consumption of a low
FODMAP sourdough rye bread, compared to a traditional sourdough rye bread [11]. In contrast, a pilot
study of 26 people with IBS who were randomised to a 7-day consumption of sourdough wheat bread
(low in FODMAPs) or yeast-fermented wheat bread showed that not only were there no differences for
any gastrointestinal symptom or inflammation markers, but, unexpectedly, symptoms of tiredness,
decreased alertness and joint symptoms were significantly worse in the sourdough wheat bread group,
compared to the yeast-fermented wheat bread. It is important to note however that this was a pilot
study with a small sample size that used non-validated questionnaires to assess symptoms [164].
Sourdough microorganisms also contain enzymes (e.g., proteases) that hydrolyse proteins, such
as gluten. As a result, studies have attempted to study the impact of sourdough bread, fermented by
specific combinations of bacteria and yeasts that hydrolyse gluten into amino acids [175], in patients
with coeliac disease. Eight paediatric patients with coeliac disease with normal values for total serum
IgA were asked to consume 200 g/day of sweet baked products made from fermented wheat flour
(containing < 10 ppm residual gluten), while continuing their usual gluten-free diet, for 60 days; six out
of eight patients completed the trial, all of whom had normal IgG and IgA-AGA and IgA-tTG antibodies
values at the end of the intervention [173]. Similarly, a study in 20 patients with coeliac disease who
were randomised to consume sourdough wheat bread (fermented with sourdough lactobacilli and
yeast proteases to hydrolyse gluten) or traditional wheat bread for 3 days, found no significant changes
in INF-γ secretion in patients consuming the fermented wheat bread, whereas the consumption of
traditional wheat bread mobilised INF-γ-secreting cells in blood [174]. However, the duration of the
intervention was only 3 days, which is not long enough to assess its impact on inflammatory markers
related to coeliac disease. An important consideration should be whether sourdough bread is indeed
gluten-free. An in vitro study showed that the level of gluten degradation depends on the strain of the
sourdough microorganisms used, and that fermentation of wheat flour does not sufficiently decrease
transglutaminase 2 binding sites on gliadin [176]. Therefore, not all gluten is hydrolysed during
fermentation and, therefore, sourdough bread made from gluten-containing flour is not considered
safe for consumption in coeliac disease.
To conclude, a small study showed no impact of sourdough bread on the stool microbiota
composition, while preliminary evidence of the impact of sourdough bread in managing gastrointestinal
symptoms stems from low-quality studies, with study sample sizes ranging from 7 to 26 participants.
Further high-quality adequately powered studies are needed in order to establish the impact of
sourdough bread on gastrointestinal health.

8. Conclusions
In summary, there is only very limited evidence on the effectiveness of most fermented foods in
gastrointestinal health, with the majority of studies being of low quality. Kefir is the fermented food
most commonly investigated in terms of its impact in gastrointestinal health, with evidence suggesting
it may be beneficial for lactose malabsorption and H. pylori eradication. No human studies have been
conducted on the impact of kombucha, tempeh and kimchi in gastrointestinal health. It is worth noting
the difficulty in undertaking and replicating fermented food studies given the significant variability of
cultures and ingredients present even within food categories, which may partly explain heterogeneous
findings. To conclude, there is insufficient evidence to determine the impact of fermented foods in
gastrointestinal health and disease.
Nutrients 2019, 11, 1806 18 of 26

Author Contributions: All authors planned the structure and content of the manuscript and reviewed the
literature. E.D. and S.R.C. wrote the initial manuscript. M.R. and K.W. critically revised the manuscript. All
authors reviewed and approved the final manuscript.
Funding: Publication of this manuscript was made possible through an unrestricted educational grant from
Danone, Paris, France to the European Society of Neurogastroenterology and Motility (ESNM), Vienna, Austria.
Conflicts of Interest: E.D. has received an education grant from Alpro, received speaker fees from Yakult and
research funding from Nestec Ltd, the Almond Board of California and the International Nut and Dried Fruit
Council. M.R. has received speaker fees from Ryvita, Biokult, Symprove and Alpro and research funding from the
Almond Board of California and the International Nut and Dried Fruit Council. K.W. has served as a consultant
for Danone, has received speaker fees from Alpro and Yakult and research funding from Clasado Biosciences,
Nestec Ltd, Almond Board of California and the International Nut and Dried Fruit Council, and is the coinventor
of a mobile app to support patients following the low FODMAP diet. SC reports no conflicts of interest.

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