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Role of Diet-Microbiome Interaction in Gastrointestinal Disorders and Strategies to Modulate Them with Microbiome-Targeted Therapies.
Jadhav, A, Bajaj, A, Xiao, Y, Markandey, M, Ahuja, V, Kashyap, PC
Annual review of nutrition. 2023;:355-383
Abstract
Diet is an important determinant of health and consequently is often implicated in the development of disease, particularly gastrointestinal (GI) diseases, given the high prevalence of meal-related symptoms. The mechanisms underlying diet-driven pathophysiology are not well understood, but recent studies suggest that gut microbiota may mediate the effect of diet on GI physiology. In this review, we focus primarily on two distinct GI diseases where the role of diet has been best studied: irritable bowel syndrome and inflammatory bowel disease. We discuss how the concurrent and sequential utilization of dietary nutrients by the host and gut microbiota determines the eventual bioactive metabolite profiles in the gut and the biological effect of these metabolites on GI physiology. We highlight several concepts that can be gleaned from these findings, such as how distinct effects of an individual metabolite can influence diverse GI diseases, the effect of similar dietary interventions on multiple disease states, and the need for extensive phenotyping and data collection to help make personalized diet recommendations.
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Adjustable Intragastric Balloon Leads to Significant Improvement in Obesity-Related Lipidome and Fecal Microbiome Profiles: A Proof-of-Concept Study.
Hussan, H, Abu Dayyeh, BK, Chen, J, Johnson, S, Riedl, KM, Grainger, EM, Brooks, J, Hinton, A, Simpson, C, Kashyap, PC
Clinical and translational gastroenterology. 2022;(7):e00508
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Abstract
INTRODUCTION Intragastric balloons (IGBs) are a safe and effective treatment for obesity. However, limited knowledge exists on the underlying biological changes with IGB placement. METHODS This single-institution study was part of an adjustable IGB randomized controlled trial. Subjects with obesity were randomized in a 2 is to 1 ratio to 32 weeks of IGB with diet/exercise counseling (n = 8) vs counseling alone (controls, n = 4). Diet/exercise counseling was continued for 24 weeks post-IGB removal to assess weight maintenance. We used mass spectrometry for nontargeted plasma lipidomics analysis and 16S rRNA sequencing to profile the fecal microbiome. RESULTS Subjects with IGBs lost 15.5% of their body weight at 32 weeks vs 2.59% for controls (P < 0.05). Maintenance of a 10.5% weight loss occurred post-IGB explant. IGB placement, followed by weight maintenance, led to a -378.9 μM/L reduction in serum free fatty acids compared with pre-IGB (95% confidence interval: 612.9, -145.0). This reduction was mainly in saturated, mono, and omega-6 fatty acids when compared with pre-IGB. Polyunsaturated phosphatidylcholines also increased after IGB placement (difference of 27 μM/L; 95% confidence interval: 1.1, 52.8). Compared with controls, saturated and omega-6 free fatty acids (linoleic and arachidonic acids) were reduced after IGB placement. The fecal microbiota changed post-IGB placement and weight maintenance vs pre-IGB (P < 0.05). Further analysis showed a possible trend toward reduced Firmicutes and increased Bacteroidetes post-IGB and counseling, a change that was not conclusively different from counseling alone. DISCUSSION IGB treatment is associated with an altered fecal microbiome profile and may have a better effect on obesity-related lipidome than counseling alone.
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The role of microbiome in pancreatic cancer.
Li, JJ, Zhu, M, Kashyap, PC, Chia, N, Tran, NH, McWilliams, RR, Bekaii-Saab, TS, Ma, WW
Cancer metastasis reviews. 2021;(3):777-789
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Abstract
Recent studies of the human microbiome have offered new insights into how the microbiome can impact cancer development and treatment. Specifically, in pancreatic ductal adenocarcinoma (PDAC), the microbiota has been shown to modulate PDAC risk, contribute to tumorigenesis, impact the tumor microenvironment, and alter treatment response. These findings provide rationale for further investigations into leveraging the microbiome to develop new strategies to diagnose and treat PDAC patients. There is growing evidence that microbiome analyses have the potential to become easily performed, non-invasive diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. More excitingly, there is now emerging interest in developing interventions based on the modulation of microbiota. Fecal microbiota transplantation, probiotics, dietary changes, and antibiotics are all potential strategies to augment the efficacy of current therapeutics and reduce toxicities. While there are still challenges to overcome, this is a rapidly growing field that holds promise for translation into clinical practice and provides a new approach to improving patient outcomes.
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AGA Technical Review on the Role of Probiotics in the Management of Gastrointestinal Disorders.
Preidis, GA, Weizman, AV, Kashyap, PC, Morgan, RL
Gastroenterology. 2020;(2):708-738.e4
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Microbiota on biotics: probiotics, prebiotics, and synbiotics to optimize growth and metabolism.
Edwards, PT, Kashyap, PC, Preidis, GA
American journal of physiology. Gastrointestinal and liver physiology. 2020;(3):G382-G390
Abstract
The early stages of the metagenomics era produced countless observational studies linking various human diseases to alterations in the gut microbiota. Only recently have we begun to decipher the causal roles that gut microbes play in many of these conditions. Despite an incomplete understanding of how gut microbes influence pathophysiology, clinical trials have tested empirically numerous microbiota-targeting therapies to prevent or treat disease. Unsurprisingly, these trials have yielded mixed results. Nonetheless, the consumer market for probiotics, prebiotics, and synbiotics continues to grow. This theme paper highlights recent discoveries of mechanisms underlying diet-microbial-host interactions as they pertain to growth and metabolism and discusses current and future applications of microbiota-targeting therapies in the context of child malnutrition as well as obesity and its metabolic comorbidities, including nonalcoholic fatty liver disease and cardiovascular disease. We also highlight current challenges and identify future directions to facilitate a more efficient and direct path to clinical impact.
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Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders.
Saffouri, GB, Shields-Cutler, RR, Chen, J, Yang, Y, Lekatz, HR, Hale, VL, Cho, JM, Battaglioli, EJ, Bhattarai, Y, Thompson, KJ, et al
Nature communications. 2019;(1):2012
Abstract
Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.
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Gut Microbial Carbohydrate Metabolism Hinders Weight Loss in Overweight Adults Undergoing Lifestyle Intervention With a Volumetric Diet.
Muñiz Pedrogo, DA, Jensen, MD, Van Dyke, CT, Murray, JA, Woods, JA, Chen, J, Kashyap, PC, Nehra, V
Mayo Clinic proceedings. 2018;93(8):1104-1110
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Plain language summary
Recent research suggests that the human gut microbiome has a role to play in the development and maintenance of obesity, by influencing metabolism, fat deposition, brain-hormone signalling and insulin sensitivity. This pilot study of 26 participants, aimed to assess whether the composition and functional aspects of the gut microbiome influence outcomes of a comprehensive weight loss programme in overweight and obese individuals in America. A success criteria of 5% weight loss over a 3 month period was established. Comparisons in the gut microbiome using fecal samples at baseline and at 3 months were made between those successfully achieving the weight loss with those that did not. Achieving the weight loss success criteria was positively associated with the presence of Phascolarctobacterium. In contrast, an increased abundance of Dialister and of genes encoding gut microbial carbohydrate-active enzymes was positively associated with a failure to lose 5% of baseline body weight after 3 months. Interestingly, Phascolarctobacterium and Dialister both belong to the same bacterial family, which suggests that a compositional shift in this family may be responsible for host carbohydrate metabolism and obesity outcomes. This study highlights the potential of influencing the gut microbiome as part of an individualised obesity management programme. However the findings need to be confirmed in a larger, cohort study over a longer duration.
Abstract
The rising incidence of obesity requires the reevaluation of our current therapeutic strategies to optimize patient outcomes. The objective of this study was to determine whether compositional and functional characteristics of the gut microbiota in adults predict responses to a comprehensive lifestyle intervention program in overweight and obese adults. We recruited 26 participants from the Mayo Clinic Obesity Treatment Research Program between August 6, 2013, and September 12, 2013, to participate in a lifestyle intervention program for weight loss. Adults aged 18 to 65 years with a body mass index of 27 to 39.9 kg/m2 and able to provide informed consent were included in the study. Fecal stool samples were obtained at baseline and after 3 months. Loss of at least 5% of baseline weight after 3 months was defined as success. Clinical characteristics and gut microbial composition and function were compared between those who achieved at least 5% and those who achieved less than 5% weight loss. After 3 months, 9 of 26 participants lost at least 5% of their weight. The mean weight loss was 7.89 kg (95% CI, 6.46-9.32 kg) in the success group and 1.51 kg (95% CI, 0.52-2.49 kg) in the less than 5% weight loss group. An increased abundance of Phascolarctobacterium was associated with success. In contrast, an increased abundance of Dialister and of genes encoding gut microbial carbohydrate-active enzymes was associated with failure to lose 5% body weight. A gut microbiota with increased capability for carbohydrate metabolism appears to be associated with decreased weight loss in overweight and obese patients undergoing a lifestyle intervention program.
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A clinical primer of the role of gut microbiome in health and disease.
Yang, AL, Kashyap, PC
Tropical gastroenterology : official journal of the Digestive Diseases Foundation. 2015;(1):1-13
Abstract
Gut microbiome represents the total microbes present in the gastrointestinal tract including the genes they encode. These microbes primarily exist in a reciprocal state with the host contributing several important functions such as carbohydrates fermentation, vitamin biosynthesis and regulation of the immune system. The gut microbiome represents a dynamic organ, which responds to changes in the host, such as genetics and age, as well as environment such as diet and antibiotics. While these microbes can adapt to change, any disturbance in this host-microbe equilibrium has the potential to initiate a cascade of events leading to a disease phenotype. In this review we highlight the emerging role of gut microbiome in different gastrointestinal and systemic diseases, the role of current therapies and development of future therapies targeting the gut microbiome as a potential mode of treatment.