The GI Microbiome in Domestic Animals – Contributions to Health and Disease
Jan S. Suchodolski, MedVet, DrMedVet, PhD, Diplomate ACVM (Immunology)
Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of
Veterinary Medicine and Biomedical Sciences, College Station, TX
(jsuchodolski@cvm.tamu.edu)
Introduction
The intestinal microbiota is defined as the consortium of all living microorganisms (bacteria,
fungi, protozoa, and viruses) within the GI tract. Until recently, traditional bacterial culture was
the routine method for identification of bacteria in the GI tract of mammals, and this method still
is useful when employed for detection of specific enteropathogens (e.g., Salmonella,
Campylobacter jejuni). However, it is now well established that the vast majority of intestinal
microbes present in the GI tract remain undetected using culture based methods.1 Novel
molecular tools (i.e., PCR and high-throughput sequencing) allow for better identification of
microbes in complex ecosystems such as the GI tract. Recent studies have revealed that the GI
tract of domestic animals (e.g., horses, dogs, and cats) is home to several hundred different
bacterial genera and probably more than a thousand bacterial phylotypes.2 The mammalian
intestine harbors estimated 1010-1014 microbial cells, approximately 10 times more than the
number of host cells. It is, therefore, obvious that this highly complex microbial ecosystem plays
a crucial role in host health and disease, as demonstrated in various studies in humans and animal
models. We are just at the beginning in being able to comprehensively describe the microbial
populations in the GI tract of domestic animals, and how they are influenced by environmental
factors.
Microbiota in health
The exact number of bacterial species in the GI tract remains unclear, partly due the difficulties
to comprehensively capture this diverse ecosystem. Recent studies have revealed approximately
200 bacterial phylotypes in the canine jejunum and it is estimated that the canine colon harbors a
few hundred to thousand bacterial phylotypes. The phyla Firmicutes, Bacteroidetes,
Proteobacteria, Actinobacteria, Spirochaetes, and Fusobacteria constitute almost 99% of all gut
microbiota in dogs and cats.2,3 Less abundant phyla are Tenericutes, Verrucomicrobia,
Cyanobacteria, and Chloroflexi. The phylum Firmicutes comprises many phylogenetically
distinct bacterial groups: Clusters XIVa and IV encompass many important short-chain fatty acid
producing bacteria (i.e., Ruminococcus spp., Faecalibacterium spp., Dorea spp.) and are the
major groups in the ileum and colon of cats and dogs.
In addition to bacteria, the GI tract harbors various fungi, archaea, protozoa, and viruses. Recent
molecular studies have provided more in depth analysis about the diversity of these
microorganisms in healthy animals, but their interactions, their influences on the host, and their
role in disease remain unclear.4
Gut microbes benefit the host through many mechanisms. They may form a defending barrier
against transient pathogens, they aid in nutrient breakdown and energy harvest from the diet,
they provide nutritional metabolites for enterocytes, and play a crucial role in the regulation of
the host immune system (Table 1). The microbial metabolites produced by the resident
microbiome are thought to be one of the most important driving forces behind the coevolution of
gastrointestinal microbiota with their host. More recent studies are attempting to study the
functional properties of the intestinal microbiota using metagenomic (i.e., shot-gun DNA
sequencing) and metabolomics approaches to better study the role of the intestinal microbiota in
GI health. Metagenomic analysis of the canine fecal microbiome revealed the most represented
functional categories of the microbiome as carbohydrate metabolism; protein metabolism; cell
wall and capsule; cofactors, vitamins, prosthetic groups and pigments; DNA metabolism; RNA
metabolism; amino acids and derivatives; and virulence.3
Microbiota in dogs and cats with gastrointestinal disease
Microbial causes of gastrointestinal disease include colonization with invading pathogens, an
imbalance (dysbiosis) caused by opportunistic bacterial residents, or an altered cross-talk
between the intestinal innate immune system and the commensal microbiota. Recent studies have
demonstrated a dysbiosis (defined as changes in the proportions of resident microbial groups
within the GI tract) is associated with acute and chronic GI diseases (e.g., idiopathic IBD in dogs
and colitis in horses).5-7 A common finding in dogs and cats with GI disease is a decrease in
bacterial groups within the Firmicutes and Bacteroidetes, and an increase in Proteobacteria (Fig.
1). In a recent study we evaluated the fecal microbiome of healthy dogs (n=180), dogs with
chronic enteropathies (CE; n=87), and dogs with acute hemorrhagic diarrhea (AHD; n=48).
Significant differences in the abundance of the evaluated bacterial groups were observed for the
disease groups when compared to the healthy dogs. Faecalibacterium spp., Turicibacter spp.,
and Ruminococcaceae were significantly decreased in CE and AHD (p<0.001 for all).
Bacteroidetes were significantly decreased in CE (p<0.001), but not different in AHD (p>0.05).
E. coli and C. perfringens were significantly increased in CE (p<0.05 and p<0.001, respectively)
and AHD (p<0.001 and p<0.01, respectively). Bifidobacterium spp. and γ-Proteobacteria were
significantly increased in CE (p<0.05 for both), but not different in dogs with AHD (p>0.05 for
both). Lactobacillus spp. and Streptococcus spp. were significantly increased in dogs with CE
(p<0.01 for both) and decreased in dogs with AHD (p<0.05 and p<0.01, respectively).
These microbiome changes may lead to altered intestinal barrier function, damage to the
intestinal brush border and enterocytes, an increased competition for nutrients and vitamins, and
to an increased deconjugation of bile acids. Of interest is that commonly depleted groups in GI
disease are Lachnospiraceae, Ruminococcaceae, and Faecalibacterium. These bacterial groups,
important producers of short-chain fatty acids, may play an important role in maintenance of
gastrointestinal health, as this leads to decreased production of SCFA (e.g., butyrate, acetate),
which may impair the capability of the host to down-regulate aberrant intestinal immune
response. The importance of some of these bacterial groups that are depleted in IBD have
recently been demonstrated in humans. For example, Faecalibacterium prausnitzii is consistently
reduced in human IBD and this bacterium has been shown to secrete metabolites with antiinflammatory properties, thereby down-regulating IL-12 and IFNγ and increasing IL-10
secretions.8
To understand the impact of bacterial dysbiosis on host immune and metabolic function, we have
recently evaluated the serum metabolic profile of dogs with idiopathic IBD. There were
significant differences in the amino acid metabolism between healthy dogs and IBD dogs,
showing the microbiome response to the oxidative stress caused by inflammation. The
metabolites cysteine, 2- hydroxybutanoic acid, and hexuronic acid increased in host response to
oxidative stress. Tryptophan metabolism decreased in IBD, potentially related to an
inflammatory cytokine driven increase in the trypthophan cleaving enzyme Indoleamine 2,3-
dioxygenase-1. Further studies are warranted to evaluate treatment modalities that may improve
the imbalances in host-bacterial metabolite profiles.
Conclusions
Recent advances in molecular diagnostics have allowed us to gain a better overview about the
microbes present in the GI tract. However, our understanding of the complex interactions
between microorganism and the host are still very rudimentary. Future studies will need to
encompass metagenomics, transcriptomics, and metabolomics to understand the crosstalk
between microbes and the host. These may allow us to develop better treatment modalities
targeted at modulating the intestinal microbiota.
Table 1. Bacterial metabolic pathways important for gastrointestinal health
Metabolic endproducts
Metabolic activities of
intestinal microbiota
Effect on host health
propionate, acetate, butyrate
carbohydrate fermentation
anti-inflammatory, energy source of enterocytes, regulation of
intestinal motility, amelioration of leaky gut barrier
retinoic acid (Vitamin A
derivate)
vitamin synthesis
important for generation of peripheral regulatory T-cells
Vitamin K2, B12, biotin, folate
vitamin synthesis
important co-factors for various metabolic pathways
ceramide
induces degradation of
sphingomyelin via alkaline
sphingomyelinase
significant role in apoptosis and in the prevention of intestinal
epithelial dysplasia and tumourigenesis
indole
degradation of the amino acid
tryptophan
increases epithelial-cell tight-junction resistance and
attenuates indicators of inflammation
secondary bile acids (cholate / deconjugation / dehydroxylation
deoxycholate)
of bile acids
taurine
bacterial deconjugation of bile
acids
decrease in intestinal absorption degradation of oxalate through
of oxalate
oxalyl CoA decarboxylase
intestinal fat absorption
facilitates fat absorption from the GI tract, important for liver
metabolism
decreases in oxalate degarding enzyme associated with
increased risk for calcium oxalate urolithiasis
ammonia
decarboxylation, deamination of
amino acids
increases associated with encephalopathy
D-lactate
carbohydrate fermentation
increases associated with encephalopathy
Figure 1. Predominant bacterial families observed in fecal samples of healthy cats (n=20) and diseased cats (n=50)
based on 454-pyrosequencing of the 16S rRNA gene. Cats with diarrhea had significant decreases in
Bacteroidaceae, Ruminococcaceae, and Veillonellaceae. Enterobacteriaceae were significantly increased. (Data
expressed as % of total 16S rRNA sequences)
Other
100%
90%
Enterobacteriaceae
80%
Helicobacteraceae
70%
Erysipelotrichaceae
Fusobacteriaceae
60%
Clostridiaceae
50%
Veillonellaceae
40%
Ruminococcaceae
30%
Lachnospiraceae
20%
Bifidobacteriaceae
10%
Prevotellaceae
0%
Healthy Cats
Cats with Diarrhea
Bacteroidaceae
References
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