Minireviews Open Access
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2016; 22(40): 8905-8909
Published online Oct 28, 2016. doi: 10.3748/wjg.v22.i40.8905
Effects of a high fat diet on intestinal microbiota and gastrointestinal diseases
Mei Zhang, Xiao-Jiao Yang
Mei Zhang, Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
Xiao-Jiao Yang, McGill University, Montreal, Quebec H3A 0G4, Canada
Author contributions: The authors equally contributed to this work.
Conflict-of-interest statement: There are no potential conflicts of interest and no financial support was given.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mei Zhang, MD, Chief Physician, Professor, Department of Gastroenterology, Xuanwu Hospital, Capital Medical University No. 45 Changchun Street, Xuanwu District, Beijing 100053, China. zhang2955@sina.com
Telephone: +86-10-83198438
Received: July 1, 2016
Peer-review started: July 4, 2016
First decision: August 2, 2016
Revised: August 15, 2016
Accepted: September 14, 2016
Article in press: September 14, 2016
Published online: October 28, 2016

Abstract

Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. Gut microbiota may be an important intermediate link, causing gastrointestinal diseases under the influence of changes in diet and genetic predisposition. To promote healthy gut microbiota and to prevent and cure gastrointestinal diseases, diets should be improved and supplemented with probiotics.

Key Words: Intestinal microbiota, Gastrointestinal diseases, High fat diet

Core tip: Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. In this review, we summarize the relationship between a high fat diet, gut microbiota and gastrointestinal diseases.



INTRODUCTION

Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases[1]. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. In this review, we summarize the relationship between a high fat diet, gut microbiota and gastrointestinal diseases.

BASIC COMPOSITION OF INTESTINAL MICROBIOTA

The intestinal tract is the primary site of bacterial colonization in the human body. These complex and diverse bacteria form the gut flora. There are more than 1000 bacterial species in the human gut and this number can reach as high as 1 × 108 species. The intestinal flora is primarily composed of anaerobes, facultative anaerobes and aerobes. Anaerobes comprise more than 99% of gut microbes. The intestinal flora of the human body primarily includes Firmicutes, Bacteroidetes, Actinomycetes, Proteobacteria, Verrucomicrobia and Archaebacteria. More than 90% are Firmicutes or Bacteroidetes. The Firmicutes, Bacteroidetes, Proteobacteria and Actinomycetes comprise 64%, 23%, 8% and 3% of the gut microbiota, respectively[2]. The intestinal flora of the human body is established in infancy and gradually stabilizes with age. By approximately 2 years of age, it is similar to the adult intestinal flora[3]. The intestinal flora composition differs by age group. The proportion of Firmicutes and Bacteroidetes in infants, adults and the elderly is 0.4, 0.9 and 0.6, respectively[4].

EFFECT OF A HIGH FAT DIET ON INTESTINAL MICROBIOTA

Diet is an important factor determining intestinal flora composition. It plays a critical role in the colonization, maturation and stability of the intestinal flora. Both animal and human experiments have demonstrated that dietary changes can rapidly affect intestinal flora structure. Within 4 d of eating a specific dietary component, the human intestinal flora composition will change significantly[1,5].

Animal experiments have indicated that dietary structure affects intestinal flora. The proportion of Bacteroidetes decreased and the proportion of Firmicutes increased, which increased the proportion of Mollicutes in the intestinal tracts of mice fed a high fat and high sugar diet compared with mice fed a low fat and high sugar diet[6]. Intestinal flora diversity is reduced in mice fed a high fat and high sugar diet. However, control diet consumption gradually reversed these changes. Furthermore, one study investigated varying proportions of dietary fatty acids in mice for 8 wk. A diet high in saturated fatty acids led to an increased proportion of intestinal Firmicutes and decreased intestinal flora diversity[7]. This study suggests that dietary fats and saturated fatty acid intake may affect intestinal flora composition. One study found that converting a low sugar, low fat diet to a high sugar, high fat diet caused a rapid decline in the number of Bacteroidetes in the intestines[8]. Another study also suggested that the number of Bacillus bifidus was reduced in mice fed a high fat diet[9]. Animal studies have demonstrated a significant reduction in the number of lactic acid bacteria, Bacillus bifidus and Enterococcus in the intestinal tract of the group fed a high fat diet. Furthermore, the phylum Bacteroidetes displayed a decreasing trend, while the Bacillus fusiformis displayed an increasing trend[10,11].

Human experiments have also demonstrated that dietary composition affects intestinal flora. Compared with Italian children who consume a large amount of plant protein, fat, sugar and starch, the proportion of Bacteroidetes in the intestinal flora of African children was high, while the proportion of Firmicutes was low[12] (Table 1).

Table 1 Effect of a high fat diet on intestinal microbiota.
DietIntestinal floraAnimal experimentsHuman experiments
High fat dietBacteroidetesDecreasedDecreased
FirmicutesIncreasedIncreased
Low fat dietBacteroidetesIncreasedIncreased
FirmicutesDecreasedDecreased
RELATIONSHIP BETWEEN INTESTINAL MICROBIOTA AND GASTROINTESTINAL DISEASES

The composition and proportion of gut microbiota are closely related to human health. Upsetting the gut microbiota equilibrium can cause enteric dysbacteriosis and a variety of gastrointestinal and systemic diseases[13].

Intestinal microbiota and inflammatory bowel disease

Inflammatory bowel disease (IBD) comprises a group of inflammatory conditions of the colon and small intestine, including Crohn’s disease (CD) and ulcerative colitis (UC), the cause and pathogeny of which are not completely understood. Gut microbiota are closely related to IBD occurrence and development. Although the specific bacteria involved in IBD have not been identified, the gut microbiota in patients with IBD differs from those of healthy individuals. One study[14] determined that the total number of mucosa-associated bacteria in the IBD group was higher than that in the control group. In the CD group, Streptococcus was dominant in the inflammatory mucosal region, while in the UC group, lactic acid Bacillus was dominant. Studies have demonstrated that the number of Faecalibacterium prausnitzii decreased in patients with CD[15]. Their secretory products have immune regulatory activity in vitro[16]. IBD pathogenesis includes intestinal flora imbalance, increased pathogenic bacteria, toxin damage to the intestinal epithelium, immune function abnormalities and immune tolerance imbalance. Intestinal bacteria can induce epithelial endoplasmic reticulum stress, leading to intestinal mucosal barrier damage and increased intestinal permeability. Probiotic supplements in patients with IBD can effectively alleviate symptoms and delay disease progress[17,18].

Intestinal microbiota and irritable bowel syndrome

Irritable bowel syndrome (IBS), affecting approximately 5%-25% of the population, comprises a group of symptoms, including abdominal pain and changes in bowel movement patterns, without any evidence of underlying damage. The mechanisms of IBS are unclear. One study found that 3%-36% of intestinal infections can cause persistent symptoms of IBS, which suggests that gut microbiota play an important role in IBS onset[19]. Intestinal flora may affect gastrointestinal motility, visceral sensitivity, the inflammatory response and the brain-gut axis, which leads to IBS. A number of studies have confirmed that the intestinal flora of patients with IBS differs from that of healthy individuals[20,21]. At present, however, intestinal flora composition results in patients with IBS have been inconsistent and some have been contradictory. These inconsistencies may be owing to differences in specimen collection, molecular detection methods or definitions of IBS[22]. The majority of studies have found that the Bacteroidetes are reduced, while the Firmicutes are increased in the intestinal flora of patients with IBS. However, it is not yet determined whether the changes in intestinal flora directly cause or are secondary to IBS. In the future, treatment of the intestinal flora imbalance may become an option for patients with IBS[23].

Intestinal microbiota and tumors

Colorectal cancer is a common gastrointestinal tumor, the incidence and mortality rates of which are increasing each year. Most colorectal cancers are due to old age, lifestyle factors and underlying genetic disorders. Additionally, changes in the gut microbiota are closely related to colorectal cancer occurrence and development[24]. Many studies have detected imbalances in the gut microbiota of patients with colorectal cancer, while those of healthy individuals are in equilibrium. Furthermore, some reports have suggested that changes in the gut microbiota can cause cancer directly. However, it is unclear which species of bacteria play a primary role in causing cancer[25-27]. There are two theories regarding the pathogenesis of colorectal cancer associated with intestinal flora. First, some intestinal bacteria may either directly or indirectly affect intestinal epithelial cells, causing genetic mutations. These bacteria are defined as “Alpha-bugs”[28]. Their direct effects include secreting toxic proteins and the indirect effects include changes in intestinal flora that are more likely to cause mucosal immune responses and changes in colonic epithelial cells. When gene mutations accumulate, it can lead to colorectal cancer. The second theory is named the “driver-passenger” model[29]. Following colorectal cancer incidence, primary pathogens (defined as “drivers”) are replaced by opportunistic pathogens (defined as “passengers”), which are more viable in the intestinal tumor microenvironment. Possible mechanisms of intestinal flora-induced colon cancer are summarized as follows: (1) the carcinogen precursor is absorbed by the stomach, then secreted into the intestinal cavity by the liver and the active ingredient is released by intestinal flora activity; (2) the carcinogen precursor in food is released by intestinal flora activity; and (3) metabolites produced by intestinal flora induce carcinogenic effects. Many studies have explored the role of probiotics in colon cancer prevention[30]; however, there is not yet a consensus.

Intestinal microbiota and liver disease

The intestinal blood flows through the portal vein system to return to the liver. The liver affects intestinal function by secreting bile into the enterohepatic circulation. The physiological link between the two organ systems is called the “intestine-liver axis”. Studies have indicated that changes in intestinal flora play an important role in liver disease incidence and progression[31]. Intestinal probiotics can improve liver disease and are now widely used in its clinical treatment[32]. Nonalcoholic fatty liver disease (NFALD) is one of the most rapidly growing chronic liver diseases. A number of studies have indicated that intestinal flora play an important role in NFALD development[33]. Bacterial overgrowth and intestinal permeability are the primary mechanisms underlying endotoxemia and inflammatory reaction-initiated liver disease. One study confirmed the relationship between intestinal bacterial overgrowth and NFALD[34]. In another study, the relationship between intestinal permeability and NFALD was demonstrated in animal experiments[35]. Alcoholic fatty liver was also associated with gut-derived endotoxemia. Specifically, ethanol intake in the intestinal tract may cause intestinal mucosal injury and intestinal flora disorder, resulting in increased endotoxin-induced intestinal epithelial permeability, bacterial translocation and endotoxemia[36]. The intestinal flora in patients with liver cirrhosis is dramatically disordered. One study demonstrated a significant decrease in Bacillus bifidus and lactic acid Bacillus in the intestinal tract of patients with liver cirrhosis, suggesting the possibility of intestinal bacterial translocation and increased infection[37]. The occurrence of primary hepatocellular carcinoma is also associated with intestinal flora imbalance[38].

CONCLUSION

In summary, gut microbiota may be an important intermediate link, causing gastrointestinal diseases under the influence of changes in diet and genetic predisposition. A diet that is high in fat, especially high in saturated and trans fat, is closely related to obesity, metabolic syndrome and gastrointestinal diseases; polyunsaturated fats such as omega-3, omega-6 and omega-9 in right proportions are suggested as substitutes. To promote healthy gut microbiota and to prevent and cure gastrointestinal diseases, diets should be improved with low fat, low sugar, high fruit and vegetable intake and complex fibers and supplemented with probiotics or increased fermented dairy product consumption, such as yogurt and buttermilk. It is essential for patients with GI diseases to not only change their dietary composition, but also to establish a healthy eating habit and pattern to promote healthy microbiota as well as to alleviate disease-associated syndromes. Maintenance of normal gut microbiota may be a potentially key means of preventing GI diseases in the future.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Gastroenterology and hepatology

Country of origin: China

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): B, B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P- Reviewer: Czubkowski P, Gobejishvili L S- Editor: Qi Y L- Editor: Roemmele A E- Editor: Zhang FF

References
1.  Tremaroli V, Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489:242-249.  [PubMed]  [DOI]
2.  Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science. 2005;308:1635-1638.  [PubMed]  [DOI]
3.  Palmer C, Bik EM, DiGiutio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5:e177.  [PubMed]  [DOI]
4.  Mariat D, Firmesse O, Levenez F, Guimarăes V, Sokol H, Doré J, Corthier G, Furet JP. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol. 2009;9:123.  [PubMed]  [DOI]
5.  David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559-563.  [PubMed]  [DOI]
6.  Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F, Wu GD. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009;137:1716-1724.e1-2.  [PubMed]  [DOI]
7.  de Wit N, Derrien M, Bosch-Vermeulen H, Oosterink E, Keshtkar S, Duval C, de Vogel-van den Bosch J, Kleerebezem M, Müller M, van der Meer R. Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine. Am J Physiol Gastrointest Liver Physiol. 2012;303:G589-G599.  [PubMed]  [DOI]
8.  Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1:6ra14.  [PubMed]  [DOI]
9.  Zhang C, Zhang M, Wang S, Han R, Cao Y, Hua W, Mao Y, Zhang X, Pang X, Wei C. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J. 2010;4:232-241.  [PubMed]  [DOI]
10.  Liu XJ, Chen QS, Yan YL. Effect of high-fat diet on intestinal flora in mice. Food Science. 2011;32:306-311.  [PubMed]  [DOI]
11.  Cao HF, Zhang JC, Wang F, Xu J, Xu HY. Intake of a high-fat diet alters intestinal flora in male SD rats. Zhongguo Weishengtaixue Zazhi. 2012;24:102-108.  [PubMed]  [DOI]
12.  De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA. 2010;107:14691-14696.  [PubMed]  [DOI]
13.  DuPont AW, DuPont HL. The intestinal microbiota and chronic disorders of the gut. Nat Rev Gastroenterol Hepatol. 2011;8:523-531.  [PubMed]  [DOI]
14.  Fyderek K, Strus M, Kowalska-Duplaga K, Gosiewski T, Wedrychowicz A, Jedynak-Wasowicz U, Sładek M, Pieczarkowski S, Adamski P, Kochan P. Mucosal bacterial microflora and mucus layer thickness in adolescents with inflammatory bowel disease. World J Gastroenterol. 2009;15:5287-5294.  [PubMed]  [DOI]
15.  Walker AW, Sanderson JD, Churcher C, Parkes GC, Hudspith BN, Rayment N, Brostoff J, Parkhill J, Dougan G, Petrovska L. High-throughput clone library analysis of the mncosa associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Mierobiol. 2011;1:7.  [PubMed]  [DOI]
16.  Noor SO, Ridgway K, Scovell L, Kemsley EK, Lund EK, Jamieson C, Johnson IT, Narbad A. Ulcerative colitis and irritable bowel patients exhibit distinct abnormalities of the gut microbiota. BMC Gastroenterol. 2010;10:134.  [PubMed]  [DOI]
17.  Cary VA, Boullata J. What is the evidence for the use of probiotics in the treatment of inflammatory bowel disease? J Clin Nurs. 2010;19:904-916.  [PubMed]  [DOI]
18.  Whelan K, Quigley EM. Probiotics in the management of irritable bowel syndrome and inflammatory bowel disease. Curr Opin Gastroenterol. 2013;29:184-189.  [PubMed]  [DOI]
19.  Spiller R, Garsed K. Postinfectious irritable bowel syndrome. Gastroenterology. 2009;136:1979-1988.  [PubMed]  [DOI]
20.  Chassard C, Dapoigny M, Scott KP, Crouzet L, Del’homme C, Marquet P, Martin JC, Pickering G, Ardid D, Eschalier A. Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome. Aliment Pharmacol Ther. 2012;35:828-838.  [PubMed]  [DOI]
21.  Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24:521-530, e248.  [PubMed]  [DOI]
22.  Parkes GC, Brostoff J, Whelan K, Sanderson JD. Gastrointestinal microbiota in irritable bowel syndrome: their role in its pathogenesis and treatment. Am J Gastroenterol. 2008;103:1557-1567.  [PubMed]  [DOI]
23.  Ohman L, Simrén M. Intestinal microbiota and its role in irritable bowel syndrome (IBS). Curr Gastroenterol Rep. 2013;15:323.  [PubMed]  [DOI]
24.  Candela M, Guidotti M, Fabbri A, Brigidi P, Franceschi C, Fiorentini C. Human intestinal microbiota: cross-talk with the host and its potential role in colorectal cancer. Crit Rev Microbiol. 2011;37:1-14.  [PubMed]  [DOI]
25.  Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, Corthier G, Tran Van Nhieu J, Furet JP. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One. 2011;6:e16393.  [PubMed]  [DOI]
26.  Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, Ojesina AI, Jung J, Bass AJ, Tabernero J. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22:292-298.  [PubMed]  [DOI]
27.  Zackular JP, Baxter NT, Iverson KD, Sadler WD, Petrosino JF, Chenb GY, Schlossa PD. The gut microbiome modulates colon tumorigenesis. MBio. 2013;4:e00692-13.  [PubMed]  [DOI]
28.  Sears CL, Pardoll DM. Perspective: alpha-bugs. their microbial partners, and the link to colon cancer. J Infect Dis. 2011;203:306-311.  [PubMed]  [DOI]
29.  Tjalsma H, Boleij A, Marchesi JR, Dutilh BE. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol. 2012;10:575-582.  [PubMed]  [DOI]
30.  Liong MT. Roles of probiotics and prebiotics in colon cancer prevention: Postulated mechanisms and in-vivo evidence. Int J Mol Sci. 2008;9:854-863.  [PubMed]  [DOI]
31.  Henao-Mejia J, Elinav E, Thaiss CA, Flavell RA. The intestinal microbiota in chronic liver disease. Adv Immunol. 2013;117:73-97.  [PubMed]  [DOI]
32.  Wang Y, Liu Y, Sidhu A, Ma Z, McClain C, Feng W. Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury. Am J Physiol Gastrointest Liver Physiol. 2012;303:G32-G41.  [PubMed]  [DOI]
33.  Cope K, Risby T, Diehl AM. Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis. Gastroenterology. 2000;119:1340-1347.  [PubMed]  [DOI]
34.  Wigg AJ, Roberts-Thomson IC, Dymock RB, McCarthy PJ, Grose RH, Cummins AG. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut. 2001;48:206-211.  [PubMed]  [DOI]
35.  Farhadi A, Gundlapalli S, Shaikh M, Frantzides C, Harrell L, Kwasny MM, Keshavarzian A. Susceptibility to gut leakiness: a possible mechanism for endotoxaemia in non-alcoholic steatohepatitis. Liver Int. 2008;28:1026-1033.  [PubMed]  [DOI]
36.  Poritz LS, Garver KI, Tilberg AF, Koltun WA. Tumor necrosis factor alpha disrupts tight junction assembly. J Surg Res. 2004;116:14-18.  [PubMed]  [DOI]
37.  Wu ZW, Ling ZX, Lu HF, Zuo J, Sheng JF, Zheng SS, Li LJ. Changes of gut bacteria and immune parameters in liver transplant recipients. Hepatobiliary Pancreat Dis Int. 2012;11:40-50.  [PubMed]  [DOI]
38.  Dapito DH, Mencin A, Gwak GY, Pradere JP, Jang MK, Mederacke I, Caviglia JM, Khiabanian H, Adeyemi A, Bataller R. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell. 2012;21:504-516.  [PubMed]  [DOI]