Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome
SummaryThe intestinal tract is inhabited by a large diverse community of microbes collectively referred to as gut microbiota. While gut microbiota provide important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease (IBD) and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multilayered mucus structures that cover the intestinal surface thus allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine 1. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro2, might be promoting the post-mid 20th century increase in IBD 3. Herein, we observed that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in WT hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition, and increased pro-inflammatory potential. Use of germ-free mice and fecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that broad use of emulsifying agents might be contributing to increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.
- Research Article
97
- 10.1039/c9fo01537j
- Jan 1, 2019
- Food & Function
Increased consumption of fruits may decrease the risk of chronic inflammatory diseases including inflammatory bowel disease (IBD). Gut microbiota dysbiosis plays an important etiological role in IBD. However, the mechanisms of action underlying the anti-inflammatory effects of dietary cranberry (Vaccinium macrocarpon) in the colon and its role on gut microbiota were unclear. In this study, we determined the anti-inflammatory efficacy of whole cranberry in a mouse model of dextran sodium sulfate (DSS)-induced colitis, as well as its effects on the structure of gut microbiota. The results showed that dietary cranberry significantly decreased the severity of colitis in DSS-treated mice, evidenced by increased colon length, and decreased disease activity and histologic score of colitis in DSS-treated mice compared to the positive control group (p < 0.05). Moreover, the colonic levels of pro-inflammatory cytokine (IL-1β, IL-6 and TNF-α) were significantly reduced by cranberry supplementation (p < 0.05). Analysis of the relative abundance of fecal microbiota in phylum and genus levels revealed that DSS treatment significantly altered the microbial structure of fecal microbiota in mice. α diversity was significantly decreased in the DSS group, compared to the healthy control group. But, cranberry treatment significantly improved DSS-induced decline in α-diversity. Moreover, cranberry treatment partially reversed the change of gut microbiota in colitic mice by increasing the abundance of potential beneficial bacteria, for example, Lactobacillus and Bifidobacterium, and decreasing the abundance of potential harmful bacteria, such as Sutterella and Bilophila. Overall, our results for the first time demonstrated that modification of gut microbiota by dietary whole cranberry might contribute to its inhibitory effects against the development of colitis in DSS-treated mice.
- Supplementary Content
32
- 10.1159/000443362
- Mar 1, 2016
- Digestive Diseases
Fecal microbiota transplantation (FMT), a process by which the normal gastrointestinal microbiota is restored, has demonstrated extraordinary cure rates for Clostridium difficile infection and low recurrence. The community of microorganisms within the human gut (or microbiota) is critical to health status and functions; therefore, together with the rise of FMT, the gastrointestinal microbiota has emerged as a ‘virtual' organ with a level of complexity comparable to that of any other organ system and capable to compete with powerful known antibiotics for the treatment of several disorders. Although treatment protocols, donor selection, stool preparation and delivery methods varied widely, with a few reports following an identical protocol, FMT has diffused to other areas where the alterations of the gut microbiota ecology (or dysbiosis) have been theorized to play a causative role, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), among several other extra-intestinal disorders (i.e. metabolic syndrome and obesity, multiple sclerosis, cardiovascular diseases). FMT can be relatively simple to perform, but a number of challenges need to be overcome before this procedure is widely accepted in clinical practice, and currently, there is no consensus between the various gastrointestinal organizations and societies regarding the FMT procedure. In this article, we describe the modern high-throughput sequencing techniques to characterize the composition of gut microbiota and the potential for therapeutics by manipulating microbiota with FMT in several gastrointestinal disorders (C. difficile-associated diarrhea, IBD and IBS), with a look on the potential future directions of FMT.
- Research Article
28
- 10.1016/j.apsb.2024.02.020
- Feb 29, 2024
- Acta Pharmaceutica Sinica B
5S-Heudelotinone alleviates experimental colitis by shaping the immune system and enhancing the intestinal barrier in a gut microbiota-dependent manner
- Research Article
96
- 10.1038/oby.2011.68
- Nov 1, 2011
- Obesity
N/A
- Supplementary Content
37
- 10.1155/2022/9999925
- Jan 31, 2022
- Gastroenterology Research and Practice
The human intestine harbors a huge number of diverse microorganisms where a variety of complex interactions take place between the microbes as well as the host and gut microbiota. Significant long-term variations in the gut microbiota (dysbiosis) have been associated with a variety of health conditions including inflammatory bowel disease (IBD). Conventional fecal microbiota transplantations (FMTs) have been utilized to treat IBD and have been proved promising. However, various limitations such as transient results, pathogen transfer, storage, and reproducibility render conventional FMT less safe and less sustainable. Defined synthetic microbial communities (SynCom) have been used to dissect the host-microbiota-associated functions using gnotobiotic animals or in vitro cell models. This review focuses on the potential use of SynCom in IBD and its advantages and relative safety over conventional FMT. Additionally, this review reinforces how various technological advances could be combined with SynCom to have a better understanding of the complex microbial interactions in various gut inflammatory diseases including IBD. Some technological advances including the availability of a gut-on-a-chip system, intestinal organoids, ex vivo intestinal cultures, AI-based refining of the microbiome structural and functional data, and multiomic approaches may help in making more practical in vitro models of the human host. Additionally, an increase in the cultured diversity from gut microbiota and the availability of their genomic information would further make the design and utilization of SynCom more feasible. Taken together, the combined use of the available knowledge of the gut microbiota in health and disease and recent technological advances and the development of defined SynCom seem to be a promising, safe, and sustainable alternative to conventional FMT in treating IBD.
- Research Article
23
- 10.4103/sjg.sjg_131_22
- Jan 1, 2023
- Saudi Journal of Gastroenterology
Fecal microbiota transplantation (FMT) restores a balanced intestinal flora, which helps to cure recurrent Clostridium difficile infections (RCDI). FMT has also been used to treat other gastrointestinal diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and chronic constipation, as well as a variety of non-GI disorders. The purpose of this review is to discuss gut microbiota and FMT treatment of GI and non-GI diseases. An imbalanced gut microbiota is known to predispose one to Clostridium difficile infections (CDI), IBD, and IBS. However, the complex role of the gut microbiota in maintaining health is a newer concept that is being increasingly studied. The microbiome plays a major role in cellular immunity and metabolism and has been implicated in the pathogenesis of non-GI autoimmune diseases, chronic fatigue syndrome, obesity, and even some neuropsychiatric disorders. Many recent studies have reported that viral gastroenteritis can affect intestinal epithelial cells, and SARS-CoV-2 virus has been identified in the stool of infected patients. FMT is a highly effective cure for RCDI, but a better understanding of the gut microbiota in maintaining health and controlled studies of FMT in a variety of conditions are needed before FMT can be accepted and used clinically.
- Research Article
12
- 10.3390/microorganisms11112806
- Nov 19, 2023
- Microorganisms
The gut microbiota play a pivotal role in human health. Dysbiosis, alterations in microbiota composition and function, is associated with gastrointestinal disorders, including inflammatory bowel disease (IBD). This international survey aimed to assess physicians' experiences, perceptions, and practices related to microbiome modulation for gastrointestinal conditions, with a focus on IBD. Results from 142 healthcare professionals, predominantly gastroenterologists, confirmed a consensus on the relevance of the gut microbiota in IBD pathogenesis. However, the utilization of microbial composition analysis and probiotics in clinical practice was limited, primarily due to the lack of standardized guidelines and supporting evidence. Physicians held conflicting views on antibiotics, recognizing their potential for inducing remission but also causing flares in IBD. Respondents also had varying opinions on the efficacy of fecal microbiota transplantation (FMT) for different gastrointestinal conditions, with higher confidence in FMT effectiveness for irritable bowel syndrome with diarrhea, pouchitis, and ulcerative colitis. Concerns on FMT included uncertainty about effect duration, administration intervals, and conflicting evidence. Donor selection was believed to be a crucial factor in FMT outcomes. This survey highlights the need for further research and evidence-based guidelines to optimize the use of microbiome-based therapies in clinical practice. As our understanding of the gut microbiome continues to evolve, these insights will contribute to more informed and personalized approaches to managing gastrointestinal disorders.
- Research Article
16
- 10.3389/fmicb.2011.00190
- Jan 1, 2011
- Frontiers in Microbiology
EDITORIAL article Front. Microbiol., 16 September 2011Sec. Cellular and Infection Microbiology - closed section https://doi.org/10.3389/fmicb.2011.00190
- Research Article
19
- 10.1007/s00284-023-03482-y
- Oct 8, 2023
- Current Microbiology
Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with several inflammatory conditions, including inflammatory bowel diseases (IBDs), and found to have an impact on gut microbiota. In fact, some randomized controlled studies suggest benefits to IBD patients, but others do not. Our aim was to review recent evidence on the effects of omega-3 on IBD and establish the contribution of the gut microbiome. Omega-3 mediate anti-inflammatory effects in IBD through various mechanisms, including suppression of NLR family pyrin domain-containing 3 (NLRP3) inflammasome, Toll-like receptor-4 (TLR4), and nucleotide-binding oligomerization domain 2 (NOD2) signaling; this results in the repression of the nuclear factor-kappa B (Nf-kB) pathway and the secretion of pro-inflammatory cytokines. Omega-3 can also affect gut microbiota and revert the bacterial community to patterns associated with healthy status by increasing short-chain fatty acid (SCFA)-producing bacteria and enhancing the mucosal gut barrier, thus promoting homeostasis. The combination of these immunoregulatory effects and anti-inflammation properties with the promotion of a balanced gut microbiome environment could suggest that omega-3 might benefit IBD patients. Considering the microbiota of IBD patients while using omega-3 might predict and improve omega-3 effectiveness. Combining omega-3 with bacteria-altering therapy, such as probiotics and fecal microbiota transplantation, may further enhance its efficacy; however, further studies are required to elucidate mechanisms and potential preventive or treatment roles of omega-3 in IBD.
- Research Article
102
- 10.1080/1040841x.2021.1876631
- Feb 12, 2021
- Critical Reviews in Microbiology
Human gut microbiota contributes to host nutrition and metabolism, sustains intestinal cell proliferation and differentiation, and modulates host immune system. The alterations in their composition lead to severe gut disorders, including inflammatory bowel disease (IBD) or inflammatory bowel syndrome (IBS). IBD including ulcerative colitis (UC) and Crohn’s disease (CD) are gamut of chronic inflammatory disorders of gut, mediated by complex interrelations among genetic, environmental, and internal factors. IBD has debateable aetiology, however in recent years, exploring the central role of a tri-directional relationship between gut microbiota, mucosal immune system, and intestinal epithelium in pathogenesis is getting the most attention. Increasing incidences and early onset explains the exponential rise in IBD burden on health-care systems. Industrialization, hypersensitivity to allergens, lifestyle, hygiene hypothesis, loss of intestinal worms, and gut microbial composition, explains this shifted rise. Hitherto, the interventions modulating gut microbiota composition, microfluidics-based in vitro gastrointestinal models, non-allergic functional foods, nutraceuticals, and faecal microbiota transplantation (FMT) from healthy donors are some of the futuristic approaches for the disease management.
- Research Article
- 10.1093/ecco-jcc/jjab076.810
- May 27, 2021
- Journal of Crohn's and Colitis
Background Normal microbiota is one of the main topic controling normal function of human organism. Microbiota changes and dysbiosis are the important factors in the pathogenesis of different digestive diseases, including inflammatory bowel diseases (IBD). The aim: estimation the intestinal microbiota changes in patients with IBD. Methods We investigated fecal samples to determine features of intestinal microbiota in 17 patients with IBD in acute phase of diseases: 10 patients with ulcerative colitis and 7 patient with Crohn’s disease, four patients received therapy with immunodiological agents. For feces analysis we used real-time polymerase chain reaction with fluorescent detection. Statistical processing was performed using the SPSS8.0 software package. Results 100% of patients showed some changes in gut microbiota. These disorders were different in patients but no any significant changes in ulcerative colitis and Crohn’s disease patients. We saw the most frequent and significant changes: 1. decrease of Lactobacillus spp. level was determined in 59% of those examined 2. increase of Bifidobacterium spp. level was determined in 47% of patients 3. changing of the ratio of Bacteroides spp./Faecalibacterium prausnitzii towards increase of Bacteroides - in 24% of patients 4. frequency of occurrence of C. difficile was 24% of patients 5. frequency of occurrence of Candida spp. was in 35% of patients. In a number of patients, increased growth of opportunistic bacteria was detected: Proteus vulgaris/mirabilis - 24%, Citrobacter spp. - 29%, Enterobacter spp. - 12%. Microboal indirect microbial markers of colon oncopathology Fusobacterium nucleatum was identified in 18% and Parvimonas micra - in 24%. F. nucleatum and P. micra have higher frequency in patient who received immimmunodiological agents. Conclusion Patients with IBD show a downward trend in Lactobacillus spp. and increasing Bifidobacterium spp., whereby lacto-containing probiotics may be recommended for such patients and Bifidobacteria-containing probiotic may be not recommended. There is also a relatively high incidence of F. nucleatum and P. micra in IBD patients, which dictates the need for dispensary surveillance of these patients not only for the purpose of controlling the onset and maintenance of remission, but also for the purpose of early detection of colorectal cancer and IBD-associated malignancies.
- Front Matter
34
- 10.1053/j.gastro.2015.05.030
- May 26, 2015
- Gastroenterology
Fecal Microbiota Transplantation for Ulcerative Colitis: Not Just Yet
- Research Article
- 10.1155/agm3/9002193
- Jan 1, 2025
- Advanced Gut & Microbiome Research
The gut microbiome is more than just the gastrointestinal tract and the digestive organ. It is a unique community of microbes, the particular composition of which may play an important role in the development of disease, including inflammatory bowel disease (IBD). Research to date has focused on the role that genetics, the immune system, and environmental conditions may play in IBD, but additional investigations are needed to fully understand the connection between gut microbiota and the development of the disease. To illuminate this connection, data were analyzed from the Integrative Human Microbiome Project from children with Crohn′s disease (CD), and these data were compared to comparable data from healthy children. Data samples were analyzed through statistical analyses including the Welch t ‐test and PERMANOVA test. Significant differences in the composition of the gut microbial communities were observed between individuals with IBD and the control group. Specifically, samples with IBD had an increased abundance o f Escherichia coli and Ruminococcus torques. Additionally, increased levels of Bacteroides fragilis were observed, indicating that elevated levels of Bacteroides fragilis , associated with the Bacteroides fragilis toxin, may have a potential role in the onset of IBD. Furthermore, CD samples exhibited decreased Chao1 richness when compared with healthy control samples. These findings signify a potential connection between the gut microbiome and the abundance of certain microbiota with IBD onset. This paper is aimed at identifying potential connections associated with the presence of specific microbiota in the gut microbiome and the manifestation of chronic disease, particularly IBD.
- Research Article
6
- 10.1016/j.phanu.2022.100303
- Jun 25, 2022
- PharmaNutrition
Modulation of intestinal immune cell responses by eubiotic or dysbiotic microbiota in inflammatory bowel diseases
- Supplementary Content
34
- 10.1159/000442921
- Mar 1, 2016
- Digestive Diseases
Introduction: Autophagy is a cellular stress response that plays key roles in physiological processes, such as adaptation to starvation, degradation of aberrant proteins or organelles, anti-microbial defense, protein secretion, and innate and adaptive immunity. Dysfunctional autophagy is recognized as a contributing factor in many chronic inflammatory diseases, including inflammatory bowel disease (IBD). Genetic studies have identified multiple IBD-associated risk loci that include genes required for autophagy, and several lines of evidence demonstrate that autophagy is impaired in IBD patients. How dysfunctional autophagy contributes to IBD onset is currently under investigation by researchers. Key Messages: Dysfunctional autophagy has been identified to play a role in IBD pathogenesis by altering processes that include (1) intracellular bacterial killing, (2) anti-microbial peptide secretion by Paneth cells, (3) pro-inflammatory cytokine production by macrophages, (4) antigen presentation by dendritic cells, (5) goblet cell function, and (6) the endoplasmic reticulum stress response in enterocytes. The overall effect of dysregulation of these processes varies by cell type, stimulus, as well as cellular context. Manipulation of the autophagic pathway may provide a new avenue in the search for effective therapies for IBD. Conclusion: Autophagy plays multiple roles in IBD pathogenesis. A better understanding of the role of autophagy in IBD patients may provide better subclassification of IBD phenotypes and novel approaches to disease management.