Science & Society
The Fiber Gap and
the Disappearing
Gut Microbiome:
Implications for
Human Nutrition
Edward C. Deehan1 and
Jens Walter1,2,*
Increasing evidence indicates that
modern lifestyle, and specifically a
Western diet, has led to a substan-
tial depletion of the human gut
microbiome. This loss is implicated
in the rampant increase of chronic
diseases, providing an incentive to
fundamentally transform human
nutrition towards being more holis-
tic and microbiome-focused.
Lifestyle-Induced Microbiome
Depletion and its Implications for
Health
Humans have evolved with dense microbial
populations that colonize their gastrointes-
tinal tract and are integral to our biology, for
example, through the provision of signals
that aid the development of the immune
system. There is convincing evidence from
research in animal models that a disruption
of this host–microbiome symbiosis leads to
an increase in immune-mediated patholo-
gies related to chronic non-communicable
diseases (NCDs), such as obesity, cardio-
vascular disease, colon cancer, allergies,
other atopic diseases (including asthma),
autism, and autoimmune diseases [1]. The
role of the gut microbiome in NCDs is diffi-
cult to test in humans, but disease risk is
epidemiologically linked to practices that
disrupt the establishment of the gut micro-
biota early in life (such as cesarean sec-
tions, antibiotics, formula feeding), and
pathologies are often associated with an
aberrant microbiome. Importantly, most
NCDs have increased substantially within
the past decades, suggesting that modern
lifestyle might have led to a loss of bacterial
symbionts that are protective [2]. In fact,
comparisons of the gut microbiota in unin-
dustrialized rural human communities from
South America, Africa, and Papua New
Guinea (which generally have a low preva-
lence of NCDs) with that of communities in
the USA and Europe provide compelling
evidence for a substantial decline of gut
microbiome diversity through industrializa-
tion [3].
A Low-Fiber Diet is a Key Driver
of Microbiome Depletion
It is likely that a combination of factors
(antibiotics, modern clinical practices,
sanitation, dietary habits) have caused
the decline in gut microbiome diversity.
However, the only factor that has been
empirically shown to be important is a diet
low in microbiota-accessible carbohy-
drates (MACs), which are indigestible die-
tary carbohydrates that become available
to the microbes that colonize the intestine.
Research in mice showed that feeding a
diet low in MACs substantially depleted
gut microbiota diversity over the duration
of only a few generations [4]. Intake of
dietary fiber, which is the main source of
MACs in the diet of adult humans, is negli-
gibly low in the Western world when com-
pared with both the diet consumed in non-
industrialized societies and that of our
ancestors [5]. Such a low-fiber diet pro-
vides insufficient nutrients for the gut
microbes, leading not only to the loss of
species reliant on these substrates but
also to a reduction in the production of
fermentation end products with important
physiological and immunological functions
[6]. In other words, by shifting to a diet that
is fundamentally different to the diet under
which the human–microbiome interrela-
tionship evolved, we might have disrupted
this symbiosis, reducing or removing the
evolutionary routed benefits provided by
the microbes. The notion that this process
might have contributed to the rise of NCDs
and a substantial degree of morbidity and
mortality provides a strong incentive to
consider attempts to conserve and poten-
tially restore the gut microbiome.
Trends in Endocrinology & Metabolism, May 2016, Vol. 27, No. 5
Dietary Fiber Can Increase
Microbiome Diversity and Prevent
NCDs, but Consumption Is Not
Sufficient
Dietary fiber and whole grains have been
shown to increase diversity of the human
fecal microbiota [7,8]. Epidemiological
studies further consistently show significant
inverse associations between dietary fiber
intake and microbiome-associated NCDs,
and all-cause mortality, and research in
animal disease models supports a benefi-
cial role. Human intervention studies are
often inconclusive, but inconsistencies
may stem from a variety of reasons that
have not yet been sufficiently considered.
First, interindividual differences in composi-
tion of the gut microbiome, which is espe-
cially pronounced in industrialized societies
[9], results in an individualized response to
dietary fiber that may increase variation in
the findings from human trials [10]. Second,
most human intervention studies are per-
formed with daily amounts of daily fiber that
are much lower than those consumed by
our ancestors, and therefore might not lead
to detectable physiological changes.
Accordingly, moving African Americans to
a traditional South African diet with a daily
dose of 55 g of dietary fiber was efficient to
improve markers of colon cancer within 2
weeks [11].
The available data indicate a considerable
potential for dietary fiber to elevate micro-
biome diversity and prevent NCDs, but
consumption is on average only half of
what is recommended in dietary guide-
lines, which is referred to as the ‘fiber
gap’ [12]. Given that host–microbiome
symbiosis evolved with a diet that con-
tained substantially more fiber than what
is currently recommended, the real ‘fiber
gap’ for optimal health and conservation
of microbial diversity might be even larger
than currently appreciated [5]. These evo-
lutionary considerations, the appreciation
of the gut microbiome's role in human
health, and especially the recent findings
on the ‘disappearing microbiome’, now
provide a clear incentive for society-
wide efforts to fundamentally change the
239
Table 1. A Nonexhaustive List of Dietary Fibers Available on the Market, Product Names, and Food Products In Which These Fibers Could Be Used
Dietary Fibers Fiber Products Potential Food Products
®
Resistant starch ActiStar RM Flour-based foods, breads, pastries, pasta, snacks
Fibersym® RWa
Hi-MAIZE® 260a
PENFIBE® RS4

Arabinoxylan Biofiber Gum Flour-based foods, beverages, soups/sauces

NAXUS®

b-Glucan B-CANTM Flour-based foods, beverages, soups/sauces

PromOat®a
Wellmune®
Yestimun®

Cellulose GRINDSTED® MCC Flour-based foods, dairy products

MICROCEL
Solka-Floc®
Vitacel®

Inulin/oligofructose Actilight® a Beverages, confectionery, preserves, dairy products, flour-based foods, soups/sauces
Frutalose® L90a
NUTRAFLORA® a
Oliggo-Fiber® DS2a
Orafti® Synergy1a

Galactooligosaccharide, Bimuno® a Beverages, confectionery, preserves, dairy products, flour-based foods, soups/sauces
xylooligosaccharide BIOLIGO® GL
Vivinal® GOSa
Longlive XOSa
NovaGreen XOS

Human milk Mum's Sweet Secret Infant formula

oligosaccharides Glycom

Polydextrose STA-LITE® a Beverages, confectionery, preserves, dairy products, flour-based foods, soups/sauces
Litesse® IIa
NUTRIOSE® FBa

Soluble corn fiber PROMITOR® a

Beverages, confectionery, preserves, dairy products, flour-based foods, soups/sauces
TM a
Alginate Algogel Beverages, confectionery, preserves, dairy products
KIMICA ALGIN
Manugel DMBa

Pectin Citrus Pectin USP Confectionery, preserves, dairy products

GENU® Pectin C74a
Unipectine®

Gum arabic/acacia gum Agri-Spray Acacia® Beverages, confectionery, preserves, dairy products, soups/sauces
EmulGold® a
FibregumTM a
Gum Arabic SD

Guar gum GuarNT® Confectionery, preserves, dairy products, soups/sauces

Ricol Rg-250
ViscogumTM Guar Guma

Fiber-rich raw materials ‘Best’ Pea Fibera Beverages, confectionery, preserves, dairy products, flour-based foods, soups/sauces
Corn Z-Trim®
Cranberry Fiber
Fibrex® Sugar Beeta
FIBRIM® Soy
Unicell® WF

Dietary fibers with established microbiota-accessible carbohydrates.

a

240 Trends in Endocrinology & Metabolism, May 2016, Vol. 27, No. 5
Western diet and significantly increase the disease-oriented health claims for food pandemics, with clear implications for
consumption of dietary fiber. ingredients or products and to communi- public health [1], clinical practices [2],
cate those to the consumer, discouraging and human nutrition [6]. We argue here
What Can Be Done to Conserve research and product development in this that we already have avenues available to
and Restore the Human area. The preservation of the microbiome enrich the food supply with dietary fiber
Microbiome? will require regulatory policies specifically (Table 1) in an attempt to restore compo-
Virtually all nutritional organizations for foods and independent to those for sition and function of the gut microbiome.
encourage consumption of dietary fiber. drugs that, while aspiring for stringent However, their successful implementa-
Despite these efforts and a general under- scientific standards, permit innovative tion will require a society-wide effort
standing of the benefits, average dietary research and an effective communication and essentially a transformation of human
fiber intake remains low – thus changes in of validated health benefits to society. nutrition away from a discipline that
dietary recommendations alone are However, even if such attempts were suc- focuses merely on meeting the nutritional
unlikely to result in significant changes in cessful, the additional costs associated needs of the human host to one that is
consumer behavior. What is necessary is with high-fiber diets would still likely pre- concerned with also nourishing the sym-
an integrated effort that involves academ- vent them from being broadly embraced, biotic microbial communities that are so
ics, the food industry, economics, nutri- as indicated by the inverse relationship essential in health.
tional policy makers, and regulatory between socioeconomic status and die- 1
Department of Agricultural, Food, and Nutritional Science,
organizations with the goal to systemati- tary fiber intake [14]. One avenue could be University of Alberta, 4-126A Li Ka Shing Centre for
cally enhance the fiber content of the food to subsidize food products with estab- Health Research Innovation and 7-142 Katz Group Center,

supply. In the USA, white flour provides lished health benefits. If done right, the
the largest portion of dietary fiber, even costs associated with promoting a
though it is a vastly suboptimal source, healthy diet are likely low compared with
with around 80% being removed during the healthcare expenditures that could be
processing [13]. Fiber supplementation of saved [15].
white flour and white flour-rich food prod-
ucts, which are ‘overused’ and the domi- Although a strategy to boost the con-
nant component of the Western diet, sumption of MACs alone would likely be
therefore constitute an untapped oppor- beneficial and could be immediately imple-
tunity to considerably increase dietary mented, this might not restore micro-
Edmonton, Alberta, T6G 2E1, Canada
2
Department of Biological Sciences, University of Alberta,
4-126A Li Ka Shing Centre for Health Research Innovation
and 7-142 Katz Group Center, Edmonton, Alberta, T6G
2E1, Canada
*Correspondence: jwalter1@ualberta.ca (J. Walter).
http://dx.doi.org/10.1016/j.tem.2016.03.001
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fiber consumption. A variety of purified biome diversity completely without
dietary fibers and fiber-rich raw materials, parallel efforts to reintroduce microbes
as well as prebiotics with established that were lost through industrialization
MACs, is already commercially available [4]. The latter could be achieved through
to produce fiber-enriched food products probiotics (food) or live biotherapeutics
(Table 1). Several of these fibers (such as (drugs). The development of such strate-
acacia gum, polydextrose, resistant gies will be challenging from a safety per-
starches, and soluble corn fiber) have spective, and it will likely take decades
been shown in human trials to be well (and adjustments in the regulatory poli-
tolerated at daily doses of at least 50 g, cies) for the first products to be imple-
and could therefore be used to substan- mented. Even if such products would
tially enhance fiber consumption without become available, microbes can only be
adverse effects. ‘reintroduced’ if humans consume a diet
that supports their growth, providing
What is needed are clinical evaluations of another rational to envisage a fundamental
fiber types, mixtures thereof, and accept- change to human diet as described
able and palatable fiber-enriched food above.
products and diets through well-
designed and rigorous randomly con- Closing Thoughts
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regulatory policies, especially in the challenges to modern society as it is
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Trends in Endocrinology & Metabolism, May 2016, Vol. 27, No. 5 241
12. Jones, J.M. (2014) CODEX-aligned dietary fiber definitions
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15. Abdullah, M.M.H. et al. (2015) Cost-of-illness analysis
reveals potential healthcare savings with reductions in type associated with CRPC-NE and how they noma [5], was significantly (P<0.0004)
2 diabetes and cardiovascular disease following recom- evolve during ADT. Remarkable work done higher in CRPC-NE (53.3%) compared with
mended intakes of dietary fiber in Canada. Front. Pharma-
col. 6, 167 by Beltran et al., published in Nature Medi- CRPC-Adeno (13.7%) tissues. Further-
cine [2], has provided an in-depth look into more, careful examination of genomic
the genomic modifications associated with domains of AR in CRPC-Adeno tumors
CRPC-NE and castration-resistant adeno- identified numerous somatic mutations,
carcinoma prostate cancer (CRPC-Adeno), amplification, and elevated expression of
Spotlight which may lead to the development of reli- AR splice variants, such as AR-V7, which
Genomic Aberrations able biomarkers for CRPC-NE. In their is clinically associated with enzalutamide
report, the authors have employed hypoth- and abiraterone acetate resistance [6].
Drive Clonal esis-driven models with an eye towards These AR-associated genomic alterations,
answering the following fundamental ques- however, were almost absent in CRPC-NE
Evolution of tions: (i) What are the critical global genomic tumors, suggesting their reliance on AR-
Neuroendocrine aberrations that distinguish CRPC-NE from independent mechanisms for growth and
CRPC-Adeno tumors? (ii) How do CRPC- proliferation.
Tumors NE tumors evolve during the course of
ADT? (iii) Can genomic features serve as In addition to defining the distinctive geno-
Akash Kumar Kaushik1 and reliable biomarkers to determine patients at mic aberrations associated with CRPC-
Arun Sreekumar1,2,3,* high risk of developing CRPC-NE tumors? NE tumors, a primary goal of this study
was to provide molecular evidence
Molecular features of castration- Results of this landmark investigation pro- regarding the evolution of CRPC-NE. Bel-
resistant neuroendocrine prostate vide a nearly complete picture of the tran et al. provide compelling evidence
cancer (CRPC-NE) are not well molecular underpinnings of CRPC-NE. that supports the plausibility of divergent
characterized. A recent study that The authors’ findings suggest an adapta- clonal evolution of CRPC-NE tumors from
investigated genomic aberrations tion of AR-positive CRPC adenocarcinoma CRPC-Adeno under stress caused by
of CRPC-NE tumors suggests their to AR-independent CRPC neuroendocrine ADT (Figure 1). Correspondingly, consis-
tumors following therapies targeting AR tent and persistent genomic aberrations
clonal evolution from CRPC ade-
signaling. including deletion/mutation of tumor sup-
nocarcinoma. Furthermore, the
pressor genes (BRAC2 and TP53) were
existence of a distinct DNA meth-
To address these questions, tumor sam- detected in tumor samples collected from
ylation profile in CRPC-NE impli- ples were collected from a broad range of temporal cases of patients with CRPC-
cates a critical role for epigenetic metastatic sites from patients with primary NE. These patients were diagnosed with
modification in the development of adenocarcinoma, CRPC-Adeno, and either localized or metastatic adenocarci-
CRPC-NE. CRPC-NE. Histological examination of tis- noma, and after ADT, patients developed
sues confirmed lower AR protein levels either CRPC-Adeno or CRPC-NE. The
Resistance to androgen deprivation ther- with concomitant downregulation of the presence of such common genomic
apy (ADT), which aims to target androgen mRNA of AR-regulated genes in CRPC- changes across multiple tumor samples
receptor (AR) signaling in metastatic pros- NE compared with CRPC-Adeno. To from the same patient suggests divergent
tate adenocarcinoma, is the root cause of further elucidate the role of additional clonal evolution of CRPC-NE from
lethal prostate cancer. Recently, a grow- genomic modifications in CRPC-NE, AR-positive CRPC adenocarcinoma.
ing body of evidence has implied the whole-exome sequencing (WES) was per- Moreover, the model of divergent clonal
emergence of AR-independent CRPC- formed on paired 114 metastatic and nor- selection also supports the evident and
NE tumors as one of the leading causes mal tissues. Interestingly, investigation of continuous overlap of mutational and
of resistance to ADT [1]. Moreover, the WES data identified a significant overlap of genomic aberrations in adenocarcinoma,
scarcity of reliable biomarkers to identify genomic aberrations between CRPC-NE CRPC-Adeno, and CRPC-NE. Although
patients who may develop CRPC-NE has and CRPC-Adeno tumors and validated informative, these genomic aberrations

242 Trends in Endocrinology & Metabolism, May 2016, Vol. 27, No. 5