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Hugenholtz 2013

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Bioactive Carbohydrates and Dietary Fibre 2 (2013) 133–142

Available online at www.sciencedirect.com

www.elsevier.com/locate/bcdf

Modulation of the microbial fermentation in the gut


by fermentable carbohydrates

Floor Hugenholtza,b,c, Jane Adair Mullaneyd,e,f, Michiel Kleerebezemb,c,g,


Hauke Smidta,b,c, Douglas Ian Rosendaled,n
a
Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
b
Netherlands Consortium for Systems Biology, University of Amsterdam, Amsterdam, The Netherlands
c
TI Food and Nutrition, Wageningen, The Netherlands
d
Food and Nutrition Group, Food Innovation, The New Zealand Institute for Plant & Food Research Limited, Palmerston
North, New Zealand
e
AgResearch, Animal Nutrition & Health, Grasslands Research Centre, Palmerston North, New Zealand
f
Riddet Institute, Massey University, Private Bag 11222, Palmerston North, New Zealand
g
Host Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands

art i cle i nfo ab st rac t

This review considers fermentable carbohydrates and their role in maintaining health
Keywords: through their availability as fuel for the gut microbiota. The microbiota possesses
Microbiota remarkably diverse function, and is likely modifiable by diet. Therefore a diet rich in
Fermentable carbohydrates varied fermentable carbohydrates such as dietary fibre, glycosylated polyphenolics,
Short chain fatty acids glucosinolates and other plant glycans, applied in a sustained fashion may promote
Health microbial diversity leading to improved health. This may be achieved by increasing the
flexibility of the microbiota's capability to interact with diverse dietary environments, or
via increasing production of short chain fatty acids (SCFAs) from the fermentation of
carbohydrates. A higher functional modular complexity is indicative of gut health, whilst
SCFAs may reduce the risk of developing gastrointestinal disorders, cancer, and cardio-
vascular disease.
& 2013 Elsevier Ltd. All rights reserved.

Contents

1. General introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134


2. The microbiota and health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
3. Fermentable carbohydrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
3.1. Dietary fibre . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
3.2. Host-derived fermentable carbohydrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
3.3. Glycosylated bioactives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
4. Short chain fatty acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
4.1. Changes in SCFA production in response to fermentable carbohydrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
4.2. Cross feeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

n
Corresponding author. Tel.: þ31 64 6 355 6158; fax: þ31 64 6 351 7050.
E-mail address: douglas.rosendale@plantandfood.co.nz (D.I. Rosendale).

2212-6198/$ - see front matter & 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bcdf.2013.09.008
134 Bioactive Carbohydrates and Dietary Fibre 2 (2013) 133 –142

5. Manipulating the system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138


Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140

1. General introduction microbiota renders it unlikely that any single nutrient is


limiting the growth of all the resident microorganisms.
The physicochemical effects of dietary fibre consumption are Nevertheless, despite the availability of diverse and complex
well recognised by the scientific community, regulatory substrates, it is dietary carbohydrate sources which we may
authorities, food manufacturers and consumers. Generally deliberately vary by exercising dietary choice, and thus use to
these “feel the benefit” attributes comprise improvements in manipulate the microbiota.
laxation: frequency, bulk and transit time. However, there are
a host of more subtle health benefits conferred by the gut
microbiota which are becoming increasingly recognised. Here 2. The microbiota and health
we focus on these microbial benefits as conferred by the
usage of fermentable carbohydrates. In this review, we con- The diverse, abundant and competitive microbiota largely
sider fermentable carbohydrates to be any carbohydrate occupy the distal regions of the intestinal tract. These
source which, for whatever reason, escapes digestion by the microorganisms become established in succession from birth
host, and passes into the large bowel intact, where it may act onwards (Maynard, Elson, Hatton, & Weaver, 2012), concur-
as a substrate for the growth and metabolic output of the rently driving the maturation of the intestinal tract as a
resident bacteria. These fermentable carbohydrates may not functioning digestive, neuroendocrine and immune organ.
necessarily fall within the current definition of dietary fibre, The makeup of this microbial consortium is driven by
or prebiotic compounds, but some may loosely fall into that external factors such as food, antibiotic therapy and maternal
category. Thus we consider not only material which meets microbiota (Thompson-Chagoyán, Maldonado, & Gil, 2007),
Codex definition of dietary fibre, but also other glycosylated and intrinsic factors such as host species (Martin et al., 2008;
compounds which consist of one or more sugar residues Rawls, Mahowald, Ley, & Gordon, 2006) and genotype
attached via glycosidic linkage to non-carbohydrate com- (Hoskins & Boulding, 1976; Makivuokko et al., 2012). Since
pounds which collectively do not meet conventional defini- the intestinal tract is the main point of contact of the host
tions of “carbohydrates” in the strictest sense, but immune system and microorganisms (Round & Mazmanian,
nevertheless are available as microbial fuel to result in the 2009), the microbiota in both local and systemic immune
microbial generation of outcomes of interest. function (and dysfunction) play an important role in immu-
This gut microbiota is diverse, highly abundant, competi- nity and health. Immune dysfunction links with metabolic
tive, metabolically active, and largely saccharolytic (Finegold, and autoimmune disorders and so deliberately modulating
Sutter, & Mathisen, 1983; Flint, Scott, Louis, & Duncan, 2012; the microbiota with fermentable carbohydrate-based food
Moore & Holdeman, 1974; Qin et al., 2010; Tasse et al., 2010). might permit modulation of systemic immunity and obesity.
Most members of the microbiota are not reliant on the Ultimately, there may be in excess of 1000 different
availability of simple sugars, but are able to derive carbon species found amongst individual adult humans, with any
and energy from the breakdown of sometimes very complex given individual possessing 4100 of these (Qin et al., 2010).
carbohydrates, alone or as a concerted effort. Substrates This complex ecosystem increases in numbers throughout
influencing and fuelling this microbiota include both food the intestinal tract, from 10 to 1000 cells per mL in the
which escapes host digestion in the upper intestinal tract, but stomach until a density of 1011 cells per gram of intestinal
also endogenous host secretions. For example, it is unlikely to contents in the large intestine (Booijink, Zoetendal,
be a coincidence that the sites of highest microbial abun- Kleerebezem, & de Vos, 2007; Walter & Ley, 2011). These form
dance are the sites of highest mucus abundance – where the a complex mixture of resident species, where a variable
main structural component of the mucus is the heavily number and proportion of transients are unable to compete
glycosylated glycoprotein mucin, acting as a barrier to protect with or displace resident (commensal) organisms in the
the underlying epithelia from damaging agents (including the synergistic associations and food chains which contribute to
microbiota) and as a substrate to allow the continued persis- determining the composition and stability of the microbiota.
tence of the microbiota in the absence of any other food So far only 20–46% of the bacteria in the gut have been
source. Also present are other oligosaccharides, peptides, cultivated. Nonetheless a range of omics-approaches – meta-
glycosaminoglycans, aliphatic lipids and steroids (Hoskins genomics, metatranscriptomics, metaproteomics, metabolo-
et al., 1985). Products of fermentation of these substrates by mics and fluxomics – of the last few decades have given the
the microbiota include short chain fatty acids (SCFA), opportunity to understand this complex ecosystem through
branched chain fatty acids (BCFA), and a range of other the GI tract much better. For example metagenomic
metabolites, such as vitamins, nitrogenous compounds, approaches have been used to assess the population and
deconjugated exogenous (phytochemicals) or endogenous functional diversity of the microbiota, while metabolomic
(bile) compounds, and others. Many of these metabolic by- approaches have been used to assess the impact of introdu-
products are in turn used by other species (the secondary cing poorly adapted microbiota across species, which have
feeders) such that food webs and food chains develop. increased our understanding of the systemic role of this
Indeed, the stable persistence of a diverse and cooperative ecosystem (Martin et al., 2007, 2009, 2008; Rajilic-Stojanovic,
Bioactive Carbohydrates and Dietary Fibre 2 (2013) 133 –142 135

Smidt, & de Vos, 2007; van den Bogert, de Vos, Zoetendal, & environments (Parter, Kashtan, & Alon, 2007). This ecological
Kleerebezem, 2011). diversity is relevant here for the gut microbiota because those
Most of the members of the resident gut microbiota can be substrate- and product-interacting genes on the periphery of
classified in four phyla: Bacteroidetes, Firmicutes, Actinobac- the networks are likely to involve carbohydrates degradation
teria and Proteobacteria, although the increasing importance and some SCFA production.
of less abundant phyla such as Verrucomicrobia, or kingdoms
such as Archaea, is becoming increasingly recognised
(Everard et al., 2013). Similarly, yeast, fungi, protozoa and 3. Fermentable carbohydrates
viruses are also present (colonisation or replication without
causing disease may define them as commensal) and exert Fermentable carbohydrates are capable of causing favourable
influence. Indeed, the role of bacteriophage in genetically changes to the microbiota (Haenen et al., 2013; van Zanten
conferring or stabilising functions within microbiome is also et al., 2012). A commonly accepted term to describe this
becoming recognised (Reyes et al., 2010). Yet it is the key process is “prebiosis”, which is the fermentation of prebiotics.
bacterial phyla, particularly the Bacteroidetes and Firmicutes, The definition of prebiotics is “non-digestible food ingredi-
which are numerically and arguably functionally dominant: ents that beneficially affect the host by selectively stimulat-
associations have been made between phyla ratios and ing the growth and/or activity of one of a limited number of
functional or differences in the microbiota, or between bacteria in the colon” (Gibson & Roberfroid, 1995). The term
relative phyla abundance and host physiology. Interestingly, prebiotics and dietary fibre (see below) are sometimes used
the carbohydrate degradation machinery of members of interchangeably; however they are not the same. Prebiotics
these two phyla appears to be polar opposites: the extra- stimulate specific bacteria in the colon, while dietary fibres
cell-associated machinery of the Bacteroidetes phyla vs. the can be fermented by a range of bacteria or not fermented at
extracellular machinery possessed by members of the Firmi- all (Ouwehand, Derrien, de Vos, Tiihonen, & Rautonen, 2005).
cutes phyla (Muñoz-Tamayo et al., 2011). The latter machin- Conversely, a diet low in fermentable carbohydrate (e.g.
ery has been proposed as key to degrading recalcitrant resistant starch), common amongst westerners, is associated
carbohydrates (celluloses and hemi-celluloses). Similarly, with colonic disorders (Scheppach, 1994).
the SCFA profiles produced by members of these two domi-
nant phyla differ, with a tendency for butyrate production by 3.1. Dietary fibre
members of the Firmicutes phyla, whilst propionate produc-
tion tends to be dominated by Bacteroidetes. The roles of Dietary fibre is, by definition, dietary polysaccharides and
these and other SCFA in gut and systemic health will be oligosaccharides that resist digestion by the human digestive
explored in more detail later. enzymes. It includes the non-starch polysaccharides portion
Overall, the microbiota possesses remarkably consistent of foods derived from plant cell walls (pectin, hemicelluloses,
function across individuals (Qin et al., 2010), albeit dependent cellulose), oligosaccharides such as fructooligosaccharides
on gross dietary differences across species (Muegge et al., derived from inulin, digestion-resistant starches, and a range
2011). Recent work employing ecological mathematical prin- of other non-digestible polysaccharides and oligosaccharides
ciples has shown that the microbiota across populations can added to food formulations to increase their fibre content.
be divided on bases of metagenomic complement into differ- Dietary fibre has been classified into soluble and insoluble
ent functional modules (how the genes within networks are fibre. Most, but not all soluble fibres from viscous solution are
grouped according to function) of varying complexity fermented in the colon. Insoluble fibres are also fermented,
(Greenblum, Turnbaugh, & Borenstein, 2012). Here it appears but include some, such as cellulose, that are fermented
that the microbiota of lean healthy individuals has a higher slowly enough to largely survive colonic transit and have a
functional modular complexity than that of obese or IBD bulking action in the colon. In some cases this is preferred as
individuals. Essentially this is simplistically represented as rapidly fermented fibre can results in uncomfortable physio-
the genetic pathways on the periphery of metabolic net- logical effects. Within the human gut microbial metagenome
works, notably those featuring the first substrates seen by the data a wide variety of carbohydrate-degrading enzyme
microbiota, and the last products produced, are mathemati- families can be found (Tasse et al., 2010). These enzymes
cally networked differently. Those of lean healthy individuals are enriched in adults compared to infants, emphasizing the
have higher numbers of functional modules (increased com- shift to richer mixture of carbohydrates in the gut. This
plexity) each containing less genes/networks, whilst obese or variety of enzymes is necessary to degrade the complex
IBD individuals possessed lower numbers of functional mod- structures present in dietary fibre. The different linkages,
ules (decreased complexity) each containing higher numbers with the combination of different mono-sugars, in the fibres
of genes/networks. Core metabolic function, shared amongst require an arsenal of different carbohydrate degrading
all members of the microbiota in all individuals (e.g. nucleo- enzymes (reviewed in Flint, Scott, Duncan, Louis, and
tide synthesis, cell division etc.), appears not to vary in Forano (2012)). Some bacteria, like the Bacteroides spp., are
modularity (Greenblum et al., 2012). This variation in com- well equipped with a range of glycoside hydrolases and are
plexity of these “peripheral” genes in the network relates to capable of switching between different substrates (Hooper,
the functional diversity of these microbiota, and the situation Midtvedt, & Gordon, 2002). However, these species are more
is analogous to other systems for which these principles have equipped to degrade soluble carbohydrates (Flint & Bayer,
been applied, e.g. obligate symbiotes have very low functional 2008). In contrast, within the family of Bifidobacteriacaea there
complexity coinciding with adaptation to low diversity are some species which are specialised to utilise only certain
136 Bioactive Carbohydrates and Dietary Fibre 2 (2013) 133 –142

groups of oligosaccharides (Scharlau et al., 2009). In practice, Glucosinolates are-D-thioglucoside-(Z)-N-hydroxyimino-


bacterial usage of substrates is also influenced by their ability sulfate compounds that contain an amino acid-derived side
to adhere to the food matrix within the gut. For example a chain (Fig. 2). Glucosinolates such as glucoraphanin from
lawn of Bacteroidetes spp. attached to a food particle and cruciferous vegetables are hydrophilic secondary plant meta-
interspersed with islands of Bifidobacteria spp. have been bolites believed to confer the plant with defence against
observed (Macfarlane & Macfarlane, 2006). predation. Glucosinolates themselves appear not to be bioac-
tive, however, upon removal of the glycoside moiety, the
resulting aglycones are bitter tasting, lipophilic, Host phase II
3.2. Host-derived fermentable carbohydrates
drug metabolism and antioxidant pathways inducing com-
pounds, such as sulforaphane (Brooks, Paton, & Vidanes,
Host carbohydrates (predominantly from the heavily glyco-
2001).
sylated mucin glycoproteins that are the main structural
Polyphenols encompass a broad class of compounds
component of the mucus layer lining the gastrointestinal
(Manach, Scalbert, Morand, Rémésy, & Jiménez, 2004) under-
tract) were thought sufficient to maintain the large bowel
going extensive modification during digestion where, like
microbiota in its original abundance and diversity in the
glucosinolates, are rendered bioactive. In contrast to glucosi-
absence of dietary carbohydrate (Attebery, Sutter, & Finegold,
nolates which become aglycones, polyphenols are generally
1972; Bounous & Devroede, 1974; Hudson, Borriello, & Hill,
found as conjugates of glucuronate or sulphate, with or
1981; Macfarlane, Hay, & Gibson, 1989; Winitz et al., 1970),
without methylation of the catechol functional group and
Now, contemporary sequencing methods may reveal com-
consequently have different biological effects from polyphe-
munity differences previously unobservable through histor-
nol aglycones such as those found in green tea catechins
ical microbiological techniques (Gerald Tannock, University
(Kroon et al., 2004).
of Otago, NZ, pers. comm.). Microbial ecological impact
Here we are specifically interested in the apparently non-
notwithstanding, mucin oligosaccharide forms a major alter-
bioactive, glycosylated, hydrophilic form, as they are poten-
nate fermentative substrate to the microbiota during a dearth
tial targets for bacterial glycosidases, and perhaps substrates
of dietary carbohydrate. A consequence of mucin oligosac-
for gut microbial growth.
charide utilisation within the mucin layer is that the highly
de-glycosylated mucin is rendered less resistant to degrada-
tion (Variyam & Hoskins, 1983), thus allowing breakdown of
4. Short chain fatty acids
the protein scaffold and access to the underlying epithelia.
Both dietary and host carbohydrate sources are ultimately
The products produced by a microbiota include bacterial fatty
catabolised to result in increased microbial biomass and
acids, de-conjugated bile acids, protein putrefaction products
production of the microbial metabolic by-products dominated
and even B vitamins (Stevens & Hume, 1998). In the simplest
by SCFAs and, with fermentable protein, BCFAs (Louis, Scott,
of terms, (SCFAs) are produced by the gut microbiota through
Duncan, & Flint, 2007).
their fermentation of carbohydrates. These are metabolised
Furthermore, the introduction of fermentable dietary car-
by the microbiota mainly via the glycolytic pathway for
bohydrate to this system results in the redistribution of some
hexoses and via the pentose phosphate pathway for pentoses
of the collective microbial degradative capability away from
resulting in pyruvate, the main precursor for SCFA
host carbohydrates towards this additional nutrient resource
(Cummings, 1981; Macfarlane & Macfarlane, 2003) (Fig. 1).
(Sonnenburg et al., 2005), while a fibre-induced decreased
Anaerobic fermentation in the gut is determined by redox
transit time combined with increased secretion of mucin
differences between substrates and products (Macfarlane &
ultimately results in faster clearance of the existing micro-
Macfarlane, 2003). This state determines which products can
biota (Tirosh & Rubinstein, 1998), and the replenishment of
be formed and thus the amount of energy that can be formed.
highly sulphated and sialylated mucin sugars (Larsen,
Some of the products, like lactate and butyrate, are also used
Moughan, & Wilson, 1993). Bacteroides thetaiotaomicron has
to get rid of the excess of electrons (Miller & Wolin, 1979).
been characterised in terms of its food and host interactions
Short chain fatty acids (SCFA) are considered to be beneficial
in vivo (Martens, Roth, Heuser, & Gordon, 2009). In particular,
fermentation products in the gut, playing an essential role in
the implications of this organism's complete switch from
the maintenance of colonic integrity and metabolism (Cook &
host-derived to food-derived carbohydrate degradation upon
Sellin, 1998). SCFAs also exert many other beneficial effects
supply of food carbohydrate, illustrates how exposing the
on the host including resistance to disease (Topping &
collective gut microbiota to carbohydrates could be applied to
Clifton, 2001), have a role in blood pressure regulation
modify gut health.
(Pluznick et al., 2013), and may be protective against cancers
by increasing cell proliferation and apoptosis (Scharlau et al.,
3.3. Glycosylated bioactives 2009). SCFAs act as energy sources (brain, heart, muscle);
increase bile salt solubility, mineral absorption, leptin pro-
Many plant compounds are glycosylated. They tend to attract duction, leptin regulation which helps to protect against
scientific attention upon loss of the sugar group resulting in obesity and metabolic disorders (Lin et al., 2012); decrease
their aglycone moieties, many of which possess bioactivity gut pH, ammonia absorption, and inhibit pathogen growth.
due in part to bioavailability: their intrinsic lipophilic proper- Specific SCFAs may reduce the risk of developing gastro-
ties allowing uptake by cells. Examples are glucosinolates and intestinal disorders, cancer, and cardiovascular disease. The
polyphenols. major three SCFAs are butyrate, acetate and propionate.
Bioactive Carbohydrates and Dietary Fibre 2 (2013) 133 –142 137

Fig. 1 – Anaerobic sugar fermentation to short chain fatty acids. Metabolites with rounded boxes are intracellular; metabolites
with rectangular boxes may be excreted outside of the cell. Black arrows show intracellular pathways; grey arrows indicate
where a bacterium may capture and process an excreted metabolite (cross-feeding).

2006). Acetate, the most highly concentrated SCFA in the


colon, has been shown (after absorption) to increase choles-
terol synthesis, while propionate has been shown to inhibit
cholesterol synthesis. Butyrate irrigation (enema) was sug-
gested in the treatment of colitis (Scheppach et al., 1992), but
determined to be ineffective later by the same group
(Scheppach et al., 1997). Other organic acids (not short chain
fatty acids, strictly speaking) include succinate and lactate.
The collective functions of the major SCFA and organic acids
are summarised in Table 1.

4.1. Changes in SCFA production in response to


fermentable carbohydrate

The amount and ratio of SCFA can be altered by specific types


of fibre (Flint & Bayer, 2008; Van den Abbeele et al., 2011).
Effects of fibres do vary between species (Ferguson, Tasman-
Fig. 2 – General structure for all glucosinolates, the dashed
Jones, Englyst, & Harris, 2000; McOrist et al., 2011). In human
line showing the site where the glucose molecule is cleaved
faecal samples RS has been seen to specifically increase
during hydrolysis (adapted from Mullaney, Ansell, Kelly, &
butyrate (McOrist et al., 2011), whereas in a rodent model,
Heyes, 2013).
different patterns for caecal SCFA level were observed,
dependent on the RS type used, while this was independent
for colonic concentrations (Ferguson et al., 2000). In a simu-
Butyrate is the main energy source for colonocytes, propio- lated human intestinal microbiota population model arabi-
nate is taken up and metabolized by the liver, and acetate is noxylan has been seen to increase in particular propionate
taken up via peripheral circulation for metabolism by per- (Grootaert et al., 2009). Further changes have been observed
ipheral tissues (Wong, de Souza, Kendall, Emam, & Jenkins, with a number of other fibre types (Table 2).
138 Bioactive Carbohydrates and Dietary Fibre 2 (2013) 133 –142

Table 1 – Summary of biological changes associated with the increased SCFA or other organic acids (Fava, Lovegrove,
Tuohy, & Gibson, 2008; Rosendale, Cookson, Roy, & Vetharaniam, 2011).

Lactate Acetate Propionate Butyrate Succinate Biological change

↑ ↑ Energy source (brain, heart, muscle)


↑ Main energy source (colonocytes)
Decreased gut pH (increased bile salt solubility, increased mineral
↑ ↑ ↑ ↑ ↑
absorption, decreased ammonia absorption, decreased pathogen growth)
↑ Anti-cancer (inhibit proliferation, induce apoptosis)
↑ Lipid metabolism (de novo lipogenesis substrate)
↑ Lipid metabolism (inhibit HMG-CoA synthase and reductase)
↑ Increased leptin production
Decreased acetate absorption and FAS synthesis resulting in decreased

hepatic lipogenesis
↑ Decreased inflammation
↑ ↑ Increase associated with obesity in mice

In addition, glucosinolates and glycosylated polyphenolics intestine Streptococcus spp. convert simple sugars into lactate
have wrought changes in SCFA profiles. For example, fer- (Booijink et al., 2007; Zoetendal et al., 2012). The lactate can be
mentation by-product profiles in the caecum of rats where used by Veillonella spp. as a carbon source and converted into
the microbiota was primed with supplements of food grade propionate and acetate. However in Clostridium perfringens
bacteria capable of deglycosylating glucosinolates and further and possibly Bifidobacterium breve the amount of lactate
acclimatised to a glucosinolate-supplemented diet had quite produced can be dependent on the availability of glucose
different profiles from rats fed basal, unsupplemented diets (Macfarlane & Macfarlane, 2003). When there is a surplus of
(Mullaney, 2013). Similarly, the SCFA profile and microbial glucose C. perfringens produces mainly lactate, since the
abundance of in vitro fermentations in the presence of lactate then functions as an electron donor. If there is a
glycosylated phenolic compounds differed from unsupple- shortage of glucose, C. perfringens switches to a high acetate
mented cultures. production, where more ATP is formed per glucose molecule.
In addition to different carbon sources leading to different In in vitro studies some of these species can grow on
SCFA profiles we know that there is significant SCFA profile glucose, and only show lactate utilisation after glucose
difference between strains of the same species. depletion (Duncan et al., 2004). In the in vivo situation this
However in the context of whole microbiota studies where might indicate that these lactate-utilising species could
the microbial information only differentiate at the genus or switch depending on the dietary availability. However, the
family level (or above), we frequently cannot consider SCFA amount of monosaccharides in the large intestine is probably
production at the strain level. Nevertheless we can attempt to not sufficient for lactate-utilisers to switch to monosacchar-
capitalize on known and commonly occurring trends during ide fermentation instead of the acetate-lactate fermentation
fermentation by a complex culture. (Cummings & Macfarlane, 1991; Duncan et al., 2004). More-
over the lactate and acetate utilisation is an important factor
4.2. Cross feeding for the gut pH homoeostasis (Duncan et al., 2004; Flint, Scott,
Louis, & Duncan, 2012). So far, the identities of the main
Indirectly fibre fermentation alters bacteria that do not players in lactate utilisation and what the main SCFA pro-
ferment dietary fibres, but are using the acetate and lactate ducts are, is still being investigated. The main lactate-
produced by others in the gut. These so called ‘Cross feeders' utilising bacteria might differ when the carbohydrate-
are organisms that cannot break down large polymers by metabolising bacteria are different species, or produce differ-
themselves but take advantage of the products of other ent metabolites, depending on the availability and type of the
organisms: these products may be polysaccharide fragments, carbon source.
or SCFA resulting from fermentation by the other organisms.
This is illustrated by an in vitro study where incorporation of a
heavy [13C] isotope label from starch into microbial RNA was 5. Manipulating the system
measured revealed that Ruminococcus spp. were the primary
starch degraders as indicated by their predominant label Overall, the microbiota possesses remarkably diverse func-
incorporation, whilst Prevotella, Eubacterium and Bifidobacter- tion, and is likely modifiable by diet. In terms of ecological
ium spp. incorporated lesser amounts of 13C, consistent with a principles, a collective microbiota's higher functional mod-
secondary feeding position or crossfeeding upon fermenta- ular complexity, consistent with high diversity environments,
tion by-products of the Ruminococcus primary primary feeders appears to correlate with healthy individuals, whilst lower
(Kovatcheva-Datchary et al., 2009). functional complexity consistent with low diversity environ-
Similarly, other studies show different phylogenetic ments, correlates with dysfunction. If this is indeed the case,
groups are capable of converting lactate or acetate and lactate then increasing the sugar residue and glycosidic linkage
to butyrate or propionate (Duncan, Louis, & Flint, 2004; variability and frequency in a sustained manner may be
Zoetendal et al., 2012) (Fig. 1). For instance, in the small sufficient to promote environmental diversity and ultimately
Bioactive Carbohydrates and Dietary Fibre 2 (2013) 133 –142 139

Table 2 – A selection of dietary fibre intervention studies and the microbial responses.

Dietary fibre Duration Mammal SCFA Molecular Bacterial changes Reference


(weeks) profiling detected
methods
Overall Specific (16S rRNA) Up Down
change acids

Resistant starch 4 Human Up Acetate DGGE; qPCR Ruminococcus bromii Abell,


(Hi Maize) and Cooke,
butyrate Bennett,
Conlon,
and
McOrist
(2008)
Resistant starch 2 Human Up Unchanged FISH Eubacterium hadrum Schwiertz,
(type 3) and Eubacterium Lehmann,
ramulus Jacobasch,
and Blaut
(2002)
Inulin and 2.3 Human Unchanged Unchanged qPCR Faecalibacterium Ramirez-
oligofructose prausnitzii and Farias et al.
Bifidobacterium spp. (2009)
Inulin (long 3 Human Unchanged Unchanged FISH Bifidobacterium spp., Bacteroides Costabile
chain) Lactobacilli spp. and spp. and/or et al. (2010)
Atopobium spp. Prevotella
spp.
Inulin 2 Human Unchanged Unchanged FISH Bifidobacterium spp. Bacteroides Kleessen
and/or et al. (2007)
Prevotella
and
Clostridium
histolyticum
Inulin 6 Humanized Up Propionate HITChip Roseburia intestinalis, Akkermansia Van den
rats (most) and Eubacterium rectale, muciniphilaa Abbeele
butyrate Anaerostipes caccae et al. (2011)
and Bifidobacteria
longum
Raffinose 3 Human Unchanged Unchanged Sequencing; F. prausnitzii, Fernando
qPCR Bifidobacterium spp. et al. (2010)
Arabinoxylan 6 Humanized Up Propionate HITChip Roseburia intestinalis, Akkermansia Van den
(long chain) rats butyrate Eubacterium rectale, muciniphilaa Abbeele
(most) Anaerostipes caccae et al. (2011)
and Bifidobacteria
longum
Arabinoxylan 3 Human Unchanged Butyrate FISH Lactobacilli, Walton,
Bacteroides, Lu, Trogh,
Eubacterium rectale Arnaut,
group, and Gibson
Faecalibacterium (2012)
prausnitzii
Arabinoxylan- 3 Human Unchanged Butyrate FISH Lactobacilli and Walton
oligosaccharides Bacteroides et al. (2012)

a
Down in caecum, where fermentation occurred, up in faeces.

increase functional modular complexity which in turn corre- nuts and seeds, essentially randomised over time, so that no
lates with gut health. As a consequence of this dietary successive meals are the same. To a large extent, this
change, there will be an increase in SCFAs and other related simulates a normal varied healthy diet.
organic acids, which may also confer health benefits. Increasing SCFA and other beneficial microbial metabo-
Finally, substrates targeting (increasing the abundance or lites in a non-specific fashion appears to be simply an out-
activity of) distinct members of the microbiota known to come of increasing non-specific fermentable carbohydrate
produce specific SCFA species of interest may be a means of consumption. Choices of fermentable carbohydrate then
addressing particular health concerns. impart a degree of selection over the acids produced. Given
Increasing environmental diversity could be brought about sufficient additional information, such as the microbial
by a diet rich in varied fermentable carbohydrates such as makeup of the individual's microbiota, we may be able to
dietary fibre, glycosylated polyphenolics, glucosinolates and make informed choices as to which members need to be
other plant glycans, applied in a sustained fashion. We increased in activity and/or abundance to yield specific
envisage a dietary regime consisting of polymolecular dietary results. For example, if increased propionate was the desired
fibre complexes such as cell walls in fruit, vegetables, cereals, response, and a sufficient Veillonella population exists, then
140 Bioactive Carbohydrates and Dietary Fibre 2 (2013) 133 –142

we could consider increasing lactate production with RS or Everard, A., Belzer, C., Geurts, L., Ouwerkerk, J. P., Druart, C.,
long-chain inulin in a carbon-rich environment, and rely on Bindels, L. B., et al. (2013). Cross-talk between Akkermansia
the Veillonella conversion of lactate to propionate by the muciniphila and intestinal epithelium controls diet-induced
obesity. Proceedings of the National Academy of Sciences USA, 110
acrylyl CoA pathway (Fig. 1), whilst in the absence of
(22), 9066–9071.
Veillonella, consider arabinoxylans in a low carbon environ-
Fava, F., Lovegrove, J. A., Tuohy, K. M., & Gibson, G. R. (2008). The
ment being directly fermented to propionate by Bacteroides via potential role of the intestinal gut microbiota in obesity and
succinate (Fig. 1). the metabolic syndrome. Food Science and Technology Bulletin:
The challenge will be to use all the information we have Functional Foods, 5(7), 71–92.
on microbial modulation with dietary fibre: to increase func- Ferguson, L. R., Tasman-Jones, C., Englyst, H., & Harris, P. J. (2000).
tional modular complexity by using diet to drive increased Comparative effects of three resistant starch preparations on
ecological diversity; or change the SCFA profile to a healthier transit time and short-chain fatty acid production in rats.
Nutrition and Cancer, 36(2), 230–237.
profile; either increased total SCFA concentrations or enhan-
Fernando, W. M., Hill, J. E., Zello, G. A., Tyler, R. T., Dahl, W. J., &
cing specific acid species concentration. Van Kessel, A. G. (2010). Diets supplemented with chickpea or
its main oligosaccharide component raffinose modify faecal
microbial composition in healthy adults. Beneficial Microbes, 1
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FH is funded by the REINFORCE project (PIRSES-GA-2009- Intestinal Flora in Health and Disease London: Academic Press,
269328) and Netherlands Consortium for Systems Biology 3–31.
(NCSB) which is part of the Netherlands Genomics Initiative Flint, H. J., & Bayer, E. A. (2008). Plant cell wall breakdown by
and the NWO. Financial support for the preparation and anaerobic microorganisms from the mammalian digestive
writing of this research article was provided to JAM by a tract. Annals of the New York Academy of Sciences, 1125, 280–288.
Flint, H. J., Scott, K. P., Duncan, S. H., Louis, P., & Forano, E. (2012).
Nga Pae O Te Maramatanga doctoral bridging grant.
Microbial degradation of complex carbohydrates in the gut.
We would like to thank John Monro for proof reading the
Gut Microbes, 3(4), 289–306.
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