Formation of propionate and butyrate by the human colonic microbiota

doi:10.1111/1462-2920.13589

Home
/
Papers
/
Formation of propionate and butyrate by the human colonic microbiota

Journal Article•DOI•

Formation of propionate and butyrate by the human colonic microbiota

01 Jan 2017-Environmental Microbiology (Environ Microbiol)-Vol. 19, Iss: 1, pp 29-41

TL;DR: This overview emphasizes the important role played by cross-feeding of intermediary metabolites (in particular lactate, succinate and 1,2-propanediol) between different gut bacteria.

read less

Abstract: The human gut microbiota ferments dietary non-digestible carbohydrates into short-chain fatty acids (SCFA). These microbial products are utilized by the host and propionate and butyrate in particular exert a range of health-promoting functions. Here an overview of the metabolic pathways utilized by gut microbes to produce these two SCFA from dietary carbohydrates and from amino acids resulting from protein breakdown is provided. This overview emphasizes the important role played by cross-feeding of intermediary metabolites (in particular lactate, succinate and 1,2-propanediol) between different gut bacteria. The ecophysiology, including growth requirements and responses to environmental factors, of major propionate and butyrate producing bacteria are discussed in relation to dietary modulation of these metabolites. A detailed understanding of SCFA metabolism by the gut microbiota is necessary to underpin effective strategies to optimize SCFA supply to the host.

...read moreread less

Citations

PDF

Open Access

More filters

Journal Article•DOI•

Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases.

[...]

Daniela Parada Venegas¹, Marjorie De la Fuente¹, Glauben Landskron¹, María-Julieta González¹, Rodrigo Quera, Gerard Dijkstra², Hermie J. M. Harmsen², Klaas Nico Faber, Marcela A. Hermoso¹ - Show less +5 more•Institutions (2)

University of Chile¹, University Medical Center Groningen²

11 Mar 2019-Frontiers in Immunology

TL;DR: An overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for Inflammatory Bowel Diseases is presented and the therapeutic potential ofSCFAs for IBD is discussed.

...read moreread less

Abstract: Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.

...read moreread less

1,732 citations

Cites background from "Formation of propionate and butyrat..."

...Bacteroidetes (gram-negative) and Firmicutes (gram-positive) are the most abundant phyla in the intestine, with members of the Bacteroidetesmainly producing acetate and propionate, while Firmicutes mostly produce butyrate in the human gut (33, 34)....
[...]
...Butyrate and propionate formation in the gut occurs mainly from carbohydrate metabolism in glycolysis, but can also take place from organic acids and amino acids metabolism (34)....
[...]
...Also, the mucin-degrading bacteria Akkermansia muciniphila (Phylum Verrucomicrobia) produces both propionate and acetate (34, 49)....
[...]

Journal Article•DOI•

Introduction to the human gut microbiota

[...]

Elizabeth Thursby¹, Nathalie Juge¹•Institutions (1)

Norwich Research Park¹

01 Jun 2017-Biochemical Journal

TL;DR: This review summarises the current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions.

...read moreread less

Abstract: The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease Multiple factors contribute to the establishment of the human gut microbiota during infancy Diet is considered as one of the main drivers in shaping the gut microbiota across the life time Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions

...read moreread less

1,708 citations

Journal Article•DOI•

Gut microbiota functions: metabolism of nutrients and other food components

[...]

Ian Rowland¹, Glenn R. Gibson¹, Almut Heinken², Karen P. Scott³, Jonathan R. Swann⁴, Ines Thiele², Kieran Tuohy - Show less +3 more•Institutions (4)

University of Reading¹, University of Luxembourg², University of Aberdeen³, Imperial College London⁴

01 Feb 2018-European Journal of Nutrition

TL;DR: This review discusses the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates, proteins, plant polyphenols, bile acids, and vitamins, and the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism.

...read moreread less

Abstract: The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays.

...read moreread less

1,294 citations

Cites background from "Formation of propionate and butyrat..."

...It is important to note that propionate and butyrate are also formed from peptide and amino-acid fermentation by certain Bacteroidetes and Firmicutes species [21]....
[...]

Journal Article•DOI•

The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

[...]

Ygor Parladore Silva¹, Andressa Bernardi¹, Rudimar Luiz Frozza¹•Institutions (1)

Oswaldo Cruz Foundation¹

31 Jan 2020-Frontiers in Endocrinology

TL;DR: How the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function is highlighted.

...read moreread less

Abstract: A substantial body of evidence supports that the gut microbiota plays a pivotal role in the regulation of metabolic, endocrine and immune functions. In recent years, there has been growing recognition of the involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly interconnected gut-brain axis. Although amazing scientific breakthroughs over the last few years have expanded our knowledge on the communication between microbes and their hosts, the underpinnings of microbiota-gut-brain crosstalk remain to be determined. Short-chain fatty acids (SCFAs), the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation. However, the underlying mechanisms through which SCFAs might influence brain physiology and behavior have not been fully elucidated. In this review, we outline the current knowledge about the involvement of SCFAs in microbiota-gut-brain interactions. We also highlight how the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function.

...read moreread less

966 citations

Cites background from "Formation of propionate and butyrat..."

...Although anaerobic fermentation of fibers is the largest source of SCFAs, acetate, propionate, and butyrate can also be produced from amino acid metabolism (68)....
[...]

Journal Article•DOI•

Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases.

[...]

Serena Sanna¹, Natalie R. van Zuydam², Natalie R. van Zuydam³, Anubha Mahajan³, Alexander Kurilshikov¹, Arnau Vich Vila¹, Urmo Võsa¹, Zlatan Mujagic⁴, Ad A.M. Masclee⁴, Daisy Jonkers⁴, Marije Oosting⁵, Leo A. B. Joosten⁵, Mihai G. Netea⁵, Lude Franke¹, Alexandra Zhernakova¹, Jingyuan Fu¹, Cisca Wijmenga⁶, Mark I. McCarthy³, Mark I. McCarthy⁷ - Show less +15 more•Institutions (7)

University Medical Center Groningen¹, Wellcome Trust Centre for Human Genetics², University of Oxford³, Maastricht University⁴, Radboud University Nijmegen⁵, University of Oslo⁶, John Radcliffe Hospital⁷

18 Feb 2019-Nature Genetics

TL;DR: Evidence of a causal effect of the gut microbiome on metabolic traits is shown and the use of MR is supported as a means to elucidate causal relationships from microbiome-wide association findings.

...read moreread less

Abstract: Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity1. However, the causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic individuals for whom genome-wide genotyping, gut metagenomic sequence and fecal short-chain fatty acid (SCFA) levels were available2, then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Using bidirectional Mendelian randomization (MR) analyses to assess causality3, we found that the host-genetic-driven increase in gut production of the SCFA butyrate was associated with improved insulin response after an oral glucose-tolerance test (P = 9.8 × 10-5), whereas abnormalities in the production or absorption of another SCFA, propionate, were causally related to an increased risk of T2D (P = 0.004). These data provide evidence of a causal effect of the gut microbiome on metabolic traits and support the use of MR as a means to elucidate causal relationships from microbiome-wide association findings.

...read moreread less

631 citations

1
2
3
4
…
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200

Collapse

References

PDF

Open Access

More filters

Journal Article•DOI•

A human gut microbial gene catalogue established by metagenomic sequencing

[...]

Junjie Qin¹, Ruiqiang Li¹, Jeroen Raes², Manimozhiyan Arumugam, Kristoffer Sølvsten Burgdorf, Chaysavanh Manichanh, Trine Nielsen, Nicolas Pons³, Florence Levenez³, Takuji Yamada, Daniel R. Mende, Junhua Li¹, Junming Xu¹, Shaochuan Li¹, Dongfang Li¹, Jianjun Cao¹, Bo Wang¹, Huiqing Liang¹, Huisong Zheng¹, Yinlong Xie¹, Julien Tap³, Patricia Lepage³, Marcelo Bertalan, Jean-Michel Batto³, Torben Hansen, Denis Le Paslier, Allan Linneberg, H. Bjørn Nielsen, Eric Pelletier, Pierre Renault³, Thomas Sicheritz-Pontén, Keith Turner⁴, Hongmei Zhu¹, Chang Yu¹, Shengting Li¹, Min Jian¹, Yan Zhou¹, Yingrui Li¹, Xiuqing Zhang¹, Songgang Li¹, Nan Qin¹, Huanming Yang¹, Jian Wang¹, Søren Brunak, Joël Doré³, Francisco Guarner⁵, Karsten Kristiansen, Oluf Pedersen, Julian Parkhill, Jean Weissenbach, Peer Bork, S. Dusko Ehrlich³, Jun Wang¹ - Show less +49 more•Institutions (5)

Beijing Genomics Institute¹, Vrije Universiteit Brussel², Institut national de la recherche agronomique³, Wellcome Trust Sanger Institute⁴, Hebron University⁵

04 Mar 2010-Nature

TL;DR: The Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals are described, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species.

...read moreread less

Abstract: To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, ~150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively

...read moreread less

9,268 citations

"Formation of propionate and butyrat..." refers background in this paper

...hallii are among the 10 most abundant species reported in the human faecal microbiota (Qin et al., 2010; Walker et al., 2011) (Table 1) and together accounted for 44% of butyryl CoA:acetate CoA-transferase sequences amplified from faecal samples of 10 healthy volunteers (Louis et al....
[...]
...E. rectale and E. hallii are among the 10 most abundant species reported in the human faecal microbiota (Qin et al., 2010; Walker et al., 2011) (Table 1) and together accounted for 44% of butyryl CoA:acetate CoA-transferase sequences amplified from faecal samples of 10 healthy volunteers (Louis et…...
[...]
...Capabilities for butyrate and propionate production among dominant bacterial species detected in faecal samples of human subjects (Qin et al., 2010; Zhernakova et al., 2016) Phylum (family) species Butyrate 1 Propionate 2...
[...]

Journal Article•DOI•

KEGG as a reference resource for gene and protein annotation

[...]

Minoru Kanehisa¹, Yoko Sato², Masayuki Kawashima², Miho Furumichi¹, Mao Tanabe¹ - Show less +1 more•Institutions (2)

Kyoto University¹, Fujitsu²

04 Jan 2016-Nucleic Acids Research

TL;DR: The KEGG GENES database now includes viruses, plasmids, and the addendum category for functionally characterized proteins that are not represented in complete genomes, and new automatic annotation servers, BlastKOalA and GhostKOALA, are made available utilizing the non-redundant pangenome data set generated from theGENES database.

...read moreread less

Abstract: KEGG (http://www.kegg.jp/ or http://www.genome.jp/kegg/) is an integrated database resource for biological interpretation of genome sequences and other high-throughput data. Molecular functions of genes and proteins are associated with ortholog groups and stored in the KEGG Orthology (KO) database. The KEGG pathway maps, BRITE hierarchies and KEGG modules are developed as networks of KO nodes, representing high-level functions of the cell and the organism. Currently, more than 4000 complete genomes are annotated with KOs in the KEGG GENES database, which can be used as a reference data set for KO assignment and subsequent reconstruction of KEGG pathways and other molecular networks. As an annotation resource, the following improvements have been made. First, each KO record is re-examined and associated with protein sequence data used in experiments of functional characterization. Second, the GENES database now includes viruses, plasmids, and the addendum category for functionally characterized proteins that are not represented in complete genomes. Third, new automatic annotation servers, BlastKOALA and GhostKOALA, are made available utilizing the non-redundant pangenome data set generated from the GENES database. As a resource for translational bioinformatics, various data sets are created for antimicrobial resistance and drug interaction networks.

...read moreread less

4,847 citations

"Formation of propionate and butyrat..." refers background in this paper

...Histidine is converted to glutamate (Potrykus et al., 2008; Kanehisa et al., 2016), which is in agreement with high levels of butyrate being formed from histidine by faecal microbiota (Smith & Macfarlane, 1997)....
[...]
...Histidine is converted to glutamate (Potrykus et al., 2008; Kanehisa et al., 2016), which is in agreement with high levels of butyrate being formed from histidine by faecal microbiota (Smith & Macfarlane, 1997)....
[...]
...2) (Barker, 1981; Smith & Macfarlane, 1997; Kanehisa et al., 2016)....
[...]
...Several routes for the breakdown of asparate exist, via alanine, threonine, oxaloacetate or fumarate (Smith & Macfarlane, 1997; Kanehisa et al., 2016) (Fig....
[...]

Journal Article•DOI•

From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites

[...]

Ara Koh¹, Filipe De Vadder¹, Petia Kovatcheva-Datchary¹, Fredrik Bäckhed², Fredrik Bäckhed¹ - Show less +1 more•Institutions (2)

University of Gothenburg¹, University of Copenhagen²

02 Jun 2016-Cell

TL;DR: Data is reviewed supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs), which affect various physiological processes and may contribute to health and disease.

...read moreread less

3,363 citations

"Formation of propionate and butyrat..." refers background in this paper

...They are taken up efficiently by the gut mucosa and have important impacts upon 38 host physiology as sources of energy, as regulators of gene expression and as signaling molecules that are 39 recognized by specific receptors (Morrison & Preston, 2016; Koh et al., 2016)....
[...]
...They are taken up efficiently by the gut mucosa and have important impacts upon host physiology as sources of energy, as regulators of gene expression and as signaling molecules that are recognized by specific receptors (Morrison & Preston, 2016; Koh et al., 2016)....
[...]

Journal Article•DOI•

Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism

[...]

Douglas J. Morrison¹, Tom Preston¹•Institutions (1)

University of Glasgow¹

10 Mar 2016-Gut microbes

TL;DR: This review aims to pull together recent findings on the role of SCFA in human metabolism to highlight the multi-faceted role ofSCFA on different metabolic systems.

...read moreread less

Abstract: The formation of SCFA is the result of a complex interplay between diet and the gut microbiota within the gut lumen environment. The discovery of receptors, across a range of cell and tissue types for which short chain fatty acids SCFA appear to be the natural ligands, has led to increased interest in SCFA as signaling molecules between the gut microbiota and the host. SCFA represent the major carbon flux from the diet through the gut microbiota to the host and evidence is emerging for a regulatory role of SCFA in local, intermediary and peripheral metabolism. However, a lack of well-designed and controlled human studies has hampered our understanding of the significance of SCFA in human metabolic health. This review aims to pull together recent findings on the role of SCFA in human metabolism to highlight the multi-faceted role of SCFA on different metabolic systems.

...read moreread less

1,898 citations

"Formation of propionate and butyrat..." refers background in this paper

...First, they differ in their fate and tissue distribution, with butyrate being used preferentially as an energy source by the gut mucosa, propionate contributing to gluconeogenesis in the liver and acetate achieving the highest systemic concentrations in blood (Morrison & Preston, 2016)....
[...]
...This brief review will focus on butyrate and propionate as these two acids are most often considered to benefit health, including protection against colorectal cancer in the case of butyrate and promotion of satiety and reduction in cholesterol in the case of propionate (Morrison & Preston, 2016)....
[...]
...They are taken up efficiently by the gut mucosa and have important impacts upon host physiology as sources of energy, as regulators of gene expression and as signaling molecules that are recognized by specific receptors (Morrison & Preston, 2016; Koh et al., 2016)....
[...]

Journal Article•DOI•

The gut microbiota, bacterial metabolites and colorectal cancer

[...]

Petra Louis¹, Georgina L. Hold¹, Harry J. Flint¹•Institutions (1)

University of Aberdeen¹

01 Oct 2014-Nature Reviews Microbiology

TL;DR: The relationship between diet, microbial metabolism and CRC is discussed and it is argued that the cumulative effects of microbial metabolites should be considered in order to better predict and prevent cancer progression.

...read moreread less

Abstract: Accumulating evidence suggests that the human intestinal microbiota contributes to the aetiology of colorectal cancer (CRC), not only via the pro-carcinogenic activities of specific pathogens but also via the influence of the wider microbial community, particularly its metabolome. Recent data have shown that the short-chain fatty acids acetate, propionate and butyrate function in the suppression of inflammation and cancer, whereas other microbial metabolites, such as secondary bile acids, promote carcinogenesis. In this Review, we discuss the relationship between diet, microbial metabolism and CRC and argue that the cumulative effects of microbial metabolites should be considered in order to better predict and prevent cancer progression.

...read moreread less

1,866 citations

"Formation of propionate and butyrat..." refers background in this paper

...New mechanisms by which SCFA regulate immune cell development and suppress inflammation have been uncovered recently (Louis et al., 2014; Richards et al., 2016)....
[...]