An Apple a Day Keeps the Doctor Away: The Effect of a Low-Fat, High-Fiber Diet on Quality of Life, Inflammation, and Dysbiosis in Patients With Ulcerative Colitis

Abstract

Fritsch J, Garces L, Quintero MA, et al. Low-fat, high-fiber diet reduces markers of inflammation and dysbiosis and improves quality of life in patients with ulcerative colitis. Clin Gastroenterol Hepatol 2021;19:1189–1199.There is a rising interest in understanding the role of diet in the treatment and prevention of inflammatory bowel disease (IBD) (J Hum Nutr Diet 2017; 30:66–72). Recent studies suggest that diets high in fruits, vegetables, whole grains, legumes, and fish, and low in processed foods and saturated fats, may be effective in both preventing and treating chronic inflammatory conditions (Nutrients 2020;12:3429; Gut 2020;69:1637–1644). This finding is supported by both the lower incidence of IBD in Southern Europe, where the consumption of a Mediterranean diet is high (Gut 2020;69:1637–1644; Crohns Colitis 2013;7:322–337) and epidemiologic data suggesting that individuals who consume a diet high in saturated fats are at increased risk of developing ulcerative colitis (UC) (Am J Gastroenterol 2011;106:563–573).With this background, Fritsch et al conducted an exploratory cross-over study examining the influence of 2 diets with differing fat contents on several clinical and biochemical end points in UC (Clin Gastroenterol Hepatol 2021;19:1189–1199). Thirty-eight patients with UC who experienced a flare in the preceding 18 months and reported a partial Mayo score of <7 were randomized to either a catered (1) low-fat, high-fiber diet (LFD) or (2) an improved standard American diet (iSAD) for 4 weeks, followed by a 2-week washout period and 4 weeks of the alternate diet. The iSAD was characterized by 35%–40% of calories from fat, as compared with 10% of calories from fat in LFD. The primary outcome was quality of life (QoL). Secondary outcomes included changes in clinical symptoms, inflammatory markers, and microbiome and metabolomic profiles.The results demonstrated improvement in QoL and clinical symptoms in both the LFD and iSAD arms (P = .001) for the 17 patients (44.7%) included in the final analysis. Further, patients reported a higher QoL while consuming the LFD as compared with the iSAD (P = .04). No significant difference in inflammatory markers was evident, although the baseline values were low. Neither diet led to increased levels of proinflammatory cytokines, but the LFD was associated with a marginal decrease in serum amyloid A (P = .07), an acute phase reactant. Stool samples demonstrated a significant shift toward Faecalibacterium prausnitzli after the LFD compared with the iSAD (P = .04), and an increase in Prevotella species after LFD compared with baseline (P = .0007). Metabolomic studies demonstrated a significant decrease in lauric acid (P = .02) and marginal decrease in myristic acid (P = .08), 2 proinflammatory saturated fatty acids, after LFD as compared with iSAD. The authors concluded that dietary interventions may benefit patients with UC.CommentDespite wide interest in investigating the role of diet as a mediator of intestinal inflammation, to date, there is little high-quality evidence to guide clinical practice with regard to diet selection for patients with IBD. Given the increasing incidence of IBD worldwide and the simultaneous increase in a Westernized lifestyle, the impact of dietary fat on intestinal inflammation in patients with IBD is an area of great interest (Gut 2014;5:776–784). Fritsch et al address the existing gap in the literature with an exploratory randomized trial comparing the LFD with the iSAD, 2 diets with a differing fat content. Interestingly, both dietary interventions were associated with an improvement in QoL. In addition, the LFD was associated with a higher QoL as compared with the iSAD, although no significant difference in clinical symptoms was evident. These findings further validate existing theory on the influence of dietary interventions in improving the lives of patients with UC and pave the way for future studies investigating the role of diet in IBD.This study’s strengths include high adherence to the catered dietary intervention, the use of validated outcome measures, and a study design in which patients acted as their own controls accounting for heterogeneity in time-invariant patient factors that may otherwise influence study findings. There are also several key points of interest to consider in interpreting the study findings and in preparation for future related work.First, as the authors mention, it is important to consider whether the increase in QoL in both arms may have been related to an improvement in dietary fiber intake, an increase in monounsaturated fatty acids or decrease in refined sugars as part of the iSAD. For example, recent studies have suggested that fiber may be a mediator of inflammation and beneficial for the prevention of IBD. A large prospective cohort study demonstrated that healthy nurses who followed a high-fiber diet had a significant decrease in the risk of Crohn’s disease development (hazard ratio, 0.59; 95% confidence interval, 0.39–0.90) (Gastroenterology 2013;145:970–977). Similarly, a meta-analysis demonstrated that consumption of fruit and vegetables was protective against the development of UC (odds ratio, 0.69 and odds ratio, 0.71, respectively) (Eur J Gastroenterol Hepatol 2015;27:623–630) Further, after reviewing 23 dietary fiber intervention studies in IBD, Wong et al concluded that dietary fiber supplementation has the ability to induce and maintain remission in IBD (Int J Mol Sci 2016;17:919). The benefit of fiber demonstrated in these studies is also supported by in vivo studies that identify specific types of fiber such as psyllium, pectin and cellulose as effective in reducing the severity of colitis in mice (Gastroenterology 2018;154:1037–1046).Second, this study is an important step in investigating the effect of diet on IBD outcomes and exploring the biochemical factors that may contribute to the relationship; however, it is also important to consider the generalizability and applicability of the dietary intervention of interest to routine practice settings. Although it is first important to understand which dietary modifications to recommend for patients with IBD, an intervention is only as effective as its feasibility and acceptability in day-to-day life. High adherence to a catered diet for two 4-week periods suggests feasibility in an ideal clinical trial setting, but the long-term feasibility of catered meals and associated costs, or the ease of purchasing and preparing selected diets are also important to consider for wider generalizability.Third, the study findings should be considered in context of the study design. The primary study end point was QoL, which is well-aligned with patients’ goals. In contrast, subjective measures such as responses to the short IBD questionnaire are prone to a high placebo response rate (Gastroenterology 2021;161:400–404). Further, patients consumed an LFD and iSAD for 4 weeks each, and QoL scores were measured during each intervention period. Although 4 weeks seems to be sufficient based on study findings to detect a statistically significant difference in QoL, it is possible that a longer period of consumption may lead to different findings. For example, because the optimal time to effect is unknown for dietary studies, evaluating a longer period of consumption of a select diet may capture changes in secondary study outcomes, such as clinical symptoms related to inflammation or inflammatory markers such as fecal calprotectin. In a prospective cohort study, for example, the median time to reach target fecal calprotectin was 11 weeks in UC (J Pediatr Gastroenterol Nutr 2019;69:466–473) Further, sustainability of QoL improvements on a LFD should be further examined.Fourth, as the authors mention, it is important to consider the limitations of the study. Although adherence to 2 catered diets was high, it is important to emphasize that 18 of the 38 patients randomized to either arm completed the study, and another patient was excluded for failing to meet criteria for medication stability because of discontinuing marijuana use. In interpreting the study findings and the potential for selection bias, in addition to preparing for follow-up studies, it is important to discuss the possible reasons for the substantial drop-out rate. On review and comparison of the study’s baseline demographics for the enrolled patients and patients who completed the study, it does seem that a greater proportion of patients who completed the study had a lower level of education as compared with enrolled patients, although it is unclear if this is statistically significant. Further, a lower proportion of patients who completed the study were using a biologic and a higher proportion had previously used steroids. This point may speak to different patient preferences and related characteristics for engagement in clinical trials, which could potentially influence study findings (e.g., perceived value, expected results, and financial benefits) (Crohn’s Colitis 360 2020;2:otaa023).Although the exact relationship between diet and IBD remains unclear, Fritsch et al demonstrated that a controlled LFD was associated with improved QoL, and statistically significant differences in some microbiome and metabolomic profiles. Although small, this study highlights the role diet may play as a mediator of inflammation in patients with IBD and supports the need for future research. Fritsch J, Garces L, Quintero MA, et al. Low-fat, high-fiber diet reduces markers of inflammation and dysbiosis and improves quality of life in patients with ulcerative colitis. Clin Gastroenterol Hepatol 2021;19:1189–1199. There is a rising interest in understanding the role of diet in the treatment and prevention of inflammatory bowel disease (IBD) (J Hum Nutr Diet 2017; 30:66–72). Recent studies suggest that diets high in fruits, vegetables, whole grains, legumes, and fish, and low in processed foods and saturated fats, may be effective in both preventing and treating chronic inflammatory conditions (Nutrients 2020;12:3429; Gut 2020;69:1637–1644). This finding is supported by both the lower incidence of IBD in Southern Europe, where the consumption of a Mediterranean diet is high (Gut 2020;69:1637–1644; Crohns Colitis 2013;7:322–337) and epidemiologic data suggesting that individuals who consume a diet high in saturated fats are at increased risk of developing ulcerative colitis (UC) (Am J Gastroenterol 2011;106:563–573). With this background, Fritsch et al conducted an exploratory cross-over study examining the influence of 2 diets with differing fat contents on several clinical and biochemical end points in UC (Clin Gastroenterol Hepatol 2021;19:1189–1199). Thirty-eight patients with UC who experienced a flare in the preceding 18 months and reported a partial Mayo score of <7 were randomized to either a catered (1) low-fat, high-fiber diet (LFD) or (2) an improved standard American diet (iSAD) for 4 weeks, followed by a 2-week washout period and 4 weeks of the alternate diet. The iSAD was characterized by 35%–40% of calories from fat, as compared with 10% of calories from fat in LFD. The primary outcome was quality of life (QoL). Secondary outcomes included changes in clinical symptoms, inflammatory markers, and microbiome and metabolomic profiles. The results demonstrated improvement in QoL and clinical symptoms in both the LFD and iSAD arms (P = .001) for the 17 patients (44.7%) included in the final analysis. Further, patients reported a higher QoL while consuming the LFD as compared with the iSAD (P = .04). No significant difference in inflammatory markers was evident, although the baseline values were low. Neither diet led to increased levels of proinflammatory cytokines, but the LFD was associated with a marginal decrease in serum amyloid A (P = .07), an acute phase reactant. Stool samples demonstrated a significant shift toward Faecalibacterium prausnitzli after the LFD compared with the iSAD (P = .04), and an increase in Prevotella species after LFD compared with baseline (P = .0007). Metabolomic studies demonstrated a significant decrease in lauric acid (P = .02) and marginal decrease in myristic acid (P = .08), 2 proinflammatory saturated fatty acids, after LFD as compared with iSAD. The authors concluded that dietary interventions may benefit patients with UC. CommentDespite wide interest in investigating the role of diet as a mediator of intestinal inflammation, to date, there is little high-quality evidence to guide clinical practice with regard to diet selection for patients with IBD. Given the increasing incidence of IBD worldwide and the simultaneous increase in a Westernized lifestyle, the impact of dietary fat on intestinal inflammation in patients with IBD is an area of great interest (Gut 2014;5:776–784). Fritsch et al address the existing gap in the literature with an exploratory randomized trial comparing the LFD with the iSAD, 2 diets with a differing fat content. Interestingly, both dietary interventions were associated with an improvement in QoL. In addition, the LFD was associated with a higher QoL as compared with the iSAD, although no significant difference in clinical symptoms was evident. These findings further validate existing theory on the influence of dietary interventions in improving the lives of patients with UC and pave the way for future studies investigating the role of diet in IBD.This study’s strengths include high adherence to the catered dietary intervention, the use of validated outcome measures, and a study design in which patients acted as their own controls accounting for heterogeneity in time-invariant patient factors that may otherwise influence study findings. There are also several key points of interest to consider in interpreting the study findings and in preparation for future related work.First, as the authors mention, it is important to consider whether the increase in QoL in both arms may have been related to an improvement in dietary fiber intake, an increase in monounsaturated fatty acids or decrease in refined sugars as part of the iSAD. For example, recent studies have suggested that fiber may be a mediator of inflammation and beneficial for the prevention of IBD. A large prospective cohort study demonstrated that healthy nurses who followed a high-fiber diet had a significant decrease in the risk of Crohn’s disease development (hazard ratio, 0.59; 95% confidence interval, 0.39–0.90) (Gastroenterology 2013;145:970–977). Similarly, a meta-analysis demonstrated that consumption of fruit and vegetables was protective against the development of UC (odds ratio, 0.69 and odds ratio, 0.71, respectively) (Eur J Gastroenterol Hepatol 2015;27:623–630) Further, after reviewing 23 dietary fiber intervention studies in IBD, Wong et al concluded that dietary fiber supplementation has the ability to induce and maintain remission in IBD (Int J Mol Sci 2016;17:919). The benefit of fiber demonstrated in these studies is also supported by in vivo studies that identify specific types of fiber such as psyllium, pectin and cellulose as effective in reducing the severity of colitis in mice (Gastroenterology 2018;154:1037–1046).Second, this study is an important step in investigating the effect of diet on IBD outcomes and exploring the biochemical factors that may contribute to the relationship; however, it is also important to consider the generalizability and applicability of the dietary intervention of interest to routine practice settings. Although it is first important to understand which dietary modifications to recommend for patients with IBD, an intervention is only as effective as its feasibility and acceptability in day-to-day life. High adherence to a catered diet for two 4-week periods suggests feasibility in an ideal clinical trial setting, but the long-term feasibility of catered meals and associated costs, or the ease of purchasing and preparing selected diets are also important to consider for wider generalizability.Third, the study findings should be considered in context of the study design. The primary study end point was QoL, which is well-aligned with patients’ goals. In contrast, subjective measures such as responses to the short IBD questionnaire are prone to a high placebo response rate (Gastroenterology 2021;161:400–404). Further, patients consumed an LFD and iSAD for 4 weeks each, and QoL scores were measured during each intervention period. Although 4 weeks seems to be sufficient based on study findings to detect a statistically significant difference in QoL, it is possible that a longer period of consumption may lead to different findings. For example, because the optimal time to effect is unknown for dietary studies, evaluating a longer period of consumption of a select diet may capture changes in secondary study outcomes, such as clinical symptoms related to inflammation or inflammatory markers such as fecal calprotectin. In a prospective cohort study, for example, the median time to reach target fecal calprotectin was 11 weeks in UC (J Pediatr Gastroenterol Nutr 2019;69:466–473) Further, sustainability of QoL improvements on a LFD should be further examined.Fourth, as the authors mention, it is important to consider the limitations of the study. Although adherence to 2 catered diets was high, it is important to emphasize that 18 of the 38 patients randomized to either arm completed the study, and another patient was excluded for failing to meet criteria for medication stability because of discontinuing marijuana use. In interpreting the study findings and the potential for selection bias, in addition to preparing for follow-up studies, it is important to discuss the possible reasons for the substantial drop-out rate. On review and comparison of the study’s baseline demographics for the enrolled patients and patients who completed the study, it does seem that a greater proportion of patients who completed the study had a lower level of education as compared with enrolled patients, although it is unclear if this is statistically significant. Further, a lower proportion of patients who completed the study were using a biologic and a higher proportion had previously used steroids. This point may speak to different patient preferences and related characteristics for engagement in clinical trials, which could potentially influence study findings (e.g., perceived value, expected results, and financial benefits) (Crohn’s Colitis 360 2020;2:otaa023).Although the exact relationship between diet and IBD remains unclear, Fritsch et al demonstrated that a controlled LFD was associated with improved QoL, and statistically significant differences in some microbiome and metabolomic profiles. Although small, this study highlights the role diet may play as a mediator of inflammation in patients with IBD and supports the need for future research. Despite wide interest in investigating the role of diet as a mediator of intestinal inflammation, to date, there is little high-quality evidence to guide clinical practice with regard to diet selection for patients with IBD. Given the increasing incidence of IBD worldwide and the simultaneous increase in a Westernized lifestyle, the impact of dietary fat on intestinal inflammation in patients with IBD is an area of great interest (Gut 2014;5:776–784). Fritsch et al address the existing gap in the literature with an exploratory randomized trial comparing the LFD with the iSAD, 2 diets with a differing fat content. Interestingly, both dietary interventions were associated with an improvement in QoL. In addition, the LFD was associated with a higher QoL as compared with the iSAD, although no significant difference in clinical symptoms was evident. These findings further validate existing theory on the influence of dietary interventions in improving the lives of patients with UC and pave the way for future studies investigating the role of diet in IBD. This study’s strengths include high adherence to the catered dietary intervention, the use of validated outcome measures, and a study design in which patients acted as their own controls accounting for heterogeneity in time-invariant patient factors that may otherwise influence study findings. There are also several key points of interest to consider in interpreting the study findings and in preparation for future related work. First, as the authors mention, it is important to consider whether the increase in QoL in both arms may have been related to an improvement in dietary fiber intake, an increase in monounsaturated fatty acids or decrease in refined sugars as part of the iSAD. For example, recent studies have suggested that fiber may be a mediator of inflammation and beneficial for the prevention of IBD. A large prospective cohort study demonstrated that healthy nurses who followed a high-fiber diet had a significant decrease in the risk of Crohn’s disease development (hazard ratio, 0.59; 95% confidence interval, 0.39–0.90) (Gastroenterology 2013;145:970–977). Similarly, a meta-analysis demonstrated that consumption of fruit and vegetables was protective against the development of UC (odds ratio, 0.69 and odds ratio, 0.71, respectively) (Eur J Gastroenterol Hepatol 2015;27:623–630) Further, after reviewing 23 dietary fiber intervention studies in IBD, Wong et al concluded that dietary fiber supplementation has the ability to induce and maintain remission in IBD (Int J Mol Sci 2016;17:919). The benefit of fiber demonstrated in these studies is also supported by in vivo studies that identify specific types of fiber such as psyllium, pectin and cellulose as effective in reducing the severity of colitis in mice (Gastroenterology 2018;154:1037–1046). Second, this study is an important step in investigating the effect of diet on IBD outcomes and exploring the biochemical factors that may contribute to the relationship; however, it is also important to consider the generalizability and applicability of the dietary intervention of interest to routine practice settings. Although it is first important to understand which dietary modifications to recommend for patients with IBD, an intervention is only as effective as its feasibility and acceptability in day-to-day life. High adherence to a catered diet for two 4-week periods suggests feasibility in an ideal clinical trial setting, but the long-term feasibility of catered meals and associated costs, or the ease of purchasing and preparing selected diets are also important to consider for wider generalizability. Third, the study findings should be considered in context of the study design. The primary study end point was QoL, which is well-aligned with patients’ goals. In contrast, subjective measures such as responses to the short IBD questionnaire are prone to a high placebo response rate (Gastroenterology 2021;161:400–404). Further, patients consumed an LFD and iSAD for 4 weeks each, and QoL scores were measured during each intervention period. Although 4 weeks seems to be sufficient based on study findings to detect a statistically significant difference in QoL, it is possible that a longer period of consumption may lead to different findings. For example, because the optimal time to effect is unknown for dietary studies, evaluating a longer period of consumption of a select diet may capture changes in secondary study outcomes, such as clinical symptoms related to inflammation or inflammatory markers such as fecal calprotectin. In a prospective cohort study, for example, the median time to reach target fecal calprotectin was 11 weeks in UC (J Pediatr Gastroenterol Nutr 2019;69:466–473) Further, sustainability of QoL improvements on a LFD should be further examined. Fourth, as the authors mention, it is important to consider the limitations of the study. Although adherence to 2 catered diets was high, it is important to emphasize that 18 of the 38 patients randomized to either arm completed the study, and another patient was excluded for failing to meet criteria for medication stability because of discontinuing marijuana use. In interpreting the study findings and the potential for selection bias, in addition to preparing for follow-up studies, it is important to discuss the possible reasons for the substantial drop-out rate. On review and comparison of the study’s baseline demographics for the enrolled patients and patients who completed the study, it does seem that a greater proportion of patients who completed the study had a lower level of education as compared with enrolled patients, although it is unclear if this is statistically significant. Further, a lower proportion of patients who completed the study were using a biologic and a higher proportion had previously used steroids. This point may speak to different patient preferences and related characteristics for engagement in clinical trials, which could potentially influence study findings (e.g., perceived value, expected results, and financial benefits) (Crohn’s Colitis 360 2020;2:otaa023). Although the exact relationship between diet and IBD remains unclear, Fritsch et al demonstrated that a controlled LFD was associated with improved QoL, and statistically significant differences in some microbiome and metabolomic profiles. Although small, this study highlights the role diet may play as a mediator of inflammation in patients with IBD and supports the need for future research.