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ObjectiveThe effects of dietary interventions on gut bacteria are ambiguous. Following a previous intervention study, we aimed to determine how differing diets impact gut bacteria and if bacterial profiles predict intervention response.DesignSixty-seven patients with IBS were randomised to traditional IBS (n=34) or low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) (n=33) diets for 4 weeks. Food intake was recorded for 4 days during screening and intervention. Faecal samples and IBS Symptom Severity Score (IBS-SSS) reports were collected before (baseline) and after intervention. A faecal microbiota dysbiosis test (GA-map Dysbiosis Test) evaluated bacterial composition. Per protocol analysis was performed on 61 patients from whom microbiome data were available.ResultsResponders (reduced IBS-SSS by ≥50) to low FODMAP, but not traditional, dietary intervention were discriminated from non-responders before and after intervention based on faecal bacterial profiles. Bacterial abundance tended to be higher in non-responders to a low FODMAP diet compared with responders before and after intervention. A low FODMAP intervention was associated with an increase in Dysbiosis Index (DI) scores in 42% of patients; while decreased DI scores were recorded in 33% of patients following a traditional IBS diet. Non-responders to a low FODMAP diet, but not a traditional IBS diet had higher DI scores than responders at baseline. Finally, while a traditional IBS diet was not associated with significant reduction of investigated bacteria, a low FODMAP diet was associated with reduced Bifidobacterium and Actinobacteria in patients, correlating with lactose consumption.ConclusionsA low FODMAP, but not a traditional IBS diet may have significant impact on faecal bacteria. Responsiveness to a low FODMAP diet intervention may be predicted by faecal bacterial profiles.Trial registration numberNCT02107625.

Background Ketogenic diet (KD) refers to any diet in which food composition induces a ketogenic state of human metabolism. Objective To assess short- and long-term efficacy, safety, and tolerability of KD [classic KD and modified Atkins diet (MAD)] in childhood drug-resistant epilepsy (DRE) and to investigate the effect of KD on electroencephalographic (EEG) features of children with DRE. Methods Forty patients diagnosed with DRE according to International League Against Epilepsy were included and randomly assigned into classic KD or MAD groups. KD was initiated after clinical, lipid profile and EEG documentation, and regular follow-up was done for 24 months. Results Out of 40 patients with DRE, 30 completed this study. Both classic KD and MAD were effective in seizure control as 60% in classic KD group and 53.33% in MAD group became seizure free, and the remaining showed ≥50% seizure reduction. Lipid profile remained within acceptable levels throughout the study period in both groups. Adverse effects were mild and managed medically with an improvement of growth parameters and EEG during the study period. Conclusions KD is an effective and safe non-pharmacologic, non-surgical therapy for the management of DRE with a positive impact on growth and EEG. Impact Both common types of KD (classic KD and MAD) are effective for DRE, but unfortunately, nonadherence and dropout rates are frequent. High serum lipid profile (cardiovascular AE) is often suspected in children following a high-fat diet, but lipid profile remained in the acceptable level up to 24 months. Therefore, KD constitutes a safe treatment. KD had a positive impact on growth, despite inconsistent results of the KD’s effect on growth. In addition to showing strong clinical effectiveness, KD also considerably decreased the frequency of interictal epileptiform discharges and enhanced the EEG background rhythm.

INTRODUCTION:Personalized management strategies are pivotal in addressing irritable bowel syndrome (IBS). This multicenter randomized controlled trial focuses on comparing the efficacy of a microbiome-based artificial intelligence-assisted personalized diet (PD) with a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (FODMAP) for IBS management.METHODS:One hundred twenty-one patients participated, with 70 assigned to the PD group and 51 to the FODMAP diet group. IBS subtypes, demographics, symptom severity (IBS-SSS), anxiety, depression, and quality of life (IBS-QOL) were evaluated. Both interventions spanned 6 weeks. The trial's primary outcome was the within-individual difference in IBS-SSS compared between intervention groups.RESULTS:For the primary outcome, there was a change in IBS-SSS of −112.7 for those in the PD group vs −99.9 for those in the FODMAP diet group (P = 0.29). Significant improvement occurred in IBS-SSS scores (P < 0.001), frequency (P < 0.001), abdominal distension (P < 0.001), and life interference (P < 0.001) in both groups. In addition, there were significant improvements in anxiety levels and IBS-QOL scores for both groups (P < 0.001). Importantly, PD was effective in reducing IBS SSS scores across all IBS subtypes IBS-Constipation (IBS-C; P < 0.001), IBS-Diarrhea (IBS-D; P = 0.01), and IBS-Mixed (IBS-M; P < 0.001) while FODMAP diet exhibited comparable improvements in IBS-C (P = 0.004) and IBS-M (P < 0.001). PD intervention significantly improved IBS-QOL scores for all subtypes (IBS-C [P < 0.001], IBS-D [P < 0.001], and IBS-M [P = 0.008]) while the FODMAP diet did so for the IBS-C (P = 0.004) and IBS-D (P = 0.022). Notably, PD intervention led to significant microbiome diversity shifts (P < 0.05) and taxa alterations compared with FODMAP diet.DISCUSSION:The artificial intelligence-assisted PD emerges as a promising approach for comprehensive IBS management. With its ability to address individual variation, the PD approach demonstrates significant symptom relief, enhanced QOL, and notable diversity shifts in the gut microbiome, making it a valuable strategy in the evolving landscape of IBS care.

The low FODMAP diet (LFD) reduces symptoms and bifidobacteria in irritable bowel syndrome (IBS). β-galactooligosaccharides (B-GOS) may reduce the symptoms and increase bifidobacteria in IBS. We investigated whether B-GOS supplementation alongside the LFD improves IBS symptoms while preventing the decline in bifidobacteria. We performed a randomized, placebo-controlled, 3-arm trial of 69 Rome III adult patients with IBS from secondary care in the United Kingdom. Patients were randomized to a sham diet with placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.4 g/d B-GOS (LFD/B-GOS) for 4 weeks. Gastrointestinal symptoms, fecal microbiota (fluorescent in situ hybridization and 16S rRNA sequencing), fecal short-chain fatty acids (gas-liquid chromatography) and pH (probe), and urine metabolites (H NMR) were analyzed. At 4 weeks, adequate symptom relief was higher in the LFD/B-GOS group (16/24, 67%) than in the control group (7/23, 30%) (odds ratio 4.6, 95% confidence interval: 1.3-15.6; P = 0.015); Bifidobacterium concentrations (log10 cells/g dry weight) were not different between LFD and LFD/B-GOS but were lower in the LFD/B-GOS (9.49 [0.73]) than in the control (9.77 [0.41], P = 0.018). A proportion of Actinobacteria was lower in LFD (1.9%, P = 0.003) and LFD/B-GOS (1.8%, P < 0.001) groups than in the control group (4.2%). Fecal butyrate was lower in the LFD (387.3, P = 0.028) and LFD/B-GOS (346.0, P = 0.007) groups than in the control group (609.2). The LFD combined with B-GOS prebiotic produced a greater symptom response than the sham diet plus placebo, but addition of 1.4 g/d B-GOS did not prevent the reduction of bifidobacteria. The LFD reduces fecal Actinobacteria and butyrate thus strict long-term use should not be advised.

Background: Alow carbohydrate diet (LCD) is more beneficial for the glycometabolism in type 2 diabetes (T2DM) and may be effective in reducing depression. Almond, which is a common nut, has been shown to effectively improve hyperglycemia and depression symptoms. This study aimed to determine the effect of an almond-based LCD (a-LCD) on depression and glycometabolism, as well as gut microbiota and fasting glucagon-like peptide 1 (GLP-1) in patients with T2DM. Methods: This was a randomized controlled trial which compared an a-LCD with a low-fat diet (LFD). Forty-five participants with T2DM at a diabetes club and the Endocrine Division of the First and Second Affiliated Hospital of Soochow University between December 2018 to December 2019 completed each dietary intervention for 3 months, including 22 in the a-LCD group and 23 in the LFD group. The indicators for depression and biochemical indicators including glycosylated hemoglobin (HbA1c), gut microbiota, and GLP-1 concentration were assessed at the baseline and third month and compared between the two groups. Results: A-LCD significantly improved depression and HbA1c (p < 0.01). Meanwhile, a-LCD significantly increased the short chain fatty acid (SCFAs)-producing bacteria Roseburia, Ruminococcus and Eubacterium. The GLP-1 concentration in the a-LCD group was higher than that in the LFD group (p < 0.05). Conclusions: A-LCD could exert a beneficial effect on depression and glycometabolism in patients with T2DM. We speculate that the role of a-LCD in improving depression in patients with T2DM may be associated with it stimulating the growth of SCFAs-producing bacteria, increasing SCFAs production and GPR43 activation, and further maintaining GLP-1 secretion. In future studies, the SCFAs and GPR43 activation should be further examined.

Abstract Objective Osteoarthritis is the most prominent form of arthritis, affecting approximately 15% of the population in the United States. Knee osteoarthritis (KOA) has become one of the leading causes of disability in older adults. Besides knee replacement, there are no curative treatments for KOA, so persistent pain is commonly treated with opioids, acetaminophen, and nonsteroidal anti-inflammatory drugs. However, these drugs have many unpleasant side effects, so there is a need for alternative forms of pain management. We sought to test the efficacy of a dietary intervention to reduce KOA. Design A randomized controlled pilot study to test the efficacy of two dietary interventions. Subjects Adults 65–75 years of age with KOA. Methods Participants were asked to follow one of two dietary interventions (low-carbohydrate [LCD], low-fat [LFD]) or continue to eat as usual (control [CTRL]) over 12 weeks. Functional pain, self-reported pain, quality of life, and depression were assessed every three weeks. Serum from before and after the diet intervention was analyzed for oxidative stress. Results Over a period of 12 weeks, the LCD reduced pain intensity and unpleasantness in some functional pain tasks, as well as self-reported pain, compared with the LFD and CTRL. The LCD also significantly reduced oxidative stress and the adipokine leptin compared with the LFD and CTRL. Reduction in oxidative stress was related to reduced functional pain. Conclusions We present evidence suggesting that oxidative stress may be related to functional pain, and lowering it through our LCD intervention could provide relief from pain and be an opioid alternative.

Background Low-carbohydrate diets (LCD) are popular for weight loss but lack evidence about micronutrient sufficiency in real-life use. This study assessed the intake and biochemical status of selected micronutrients in people voluntarily following LCDs. Methods A cross-sectional study was conducted (2018-20) among 98 adults recruited as self-reporting either LCD ( n  = 49) or diets not restricting carbohydrates (controls; n  = 49). Diets were assessed using the 130-item EPIC-Norfolk food-frequency questionnaire. Red-blood-cell thiamine diphosphate (TDP) was measured for thiamine status using HPLC. Plasma magnesium, zinc, copper, and selenium were measured using inductively coupled plasma mass spectrometry. Between-group biomarker comparisons were conducted using ANCOVA and adjusted for age, sex, body mass index (BMI), and diabetes status. Results LCD-followers (26% male, median age 36 years, median BMI 24.2 kg/m 2 ) reported adhering to LCDs for a median duration of 9 months (IQR 4–36). The most followed LCD type was ‘their own variations of LCD’ (30%), followed by ketogenic (23%), ‘palaeolithic’ (15%), and Atkins diets (8%). Among controls, 41% were male (median age 27 years, median BMI 23 kg/m 2 ). Median macronutrient intakes for LCD vs control groups were carbohydrate 16%Energy (E) vs. 50%E; protein 25%E vs. 19%E; and fat 55%E vs 34%E (saturated fat 18%E vs. 11%E). Two-thirds of LCD followers (32/49) and half of the controls (24/49) reported some use of dietary supplements ( p  = 0.19). Among LCD-followers, assessing from food data only, 21 (43%) failed to meet the reference nutrient intake (RNI) for thiamine (vs.14% controls, p  = 0.002). When thiamine from supplementation (single- or multivitamin) was included, there appeared to be no difference in thiamine intake between groups. Still, red-blood-cell TDP was lower in LCD-followers than controls (407 ± 91 vs. 633 ± 234 ng/gHb, p  < 0.001). Three LCD-followers were thiamine-deficient (RBC thiamine < 275 ng/gHb) vs. one control. There were no significant differences in dietary intakes or plasma concentrations of magnesium, zinc, copper, and selenium between groups. Conclusions Following LCDs is associated with lower thiamine intake and TDP status than diets without carbohydrate restriction, incompletely corrected by supplement use. These data, coupled with a lack of RCT evidence on body weight control, do not support recommending LCDs for weight management without appropriate guidance and diet supplementation.

Weight change trajectory from diet and lifestyle interventions typically involves rapid weight loss followed by a weight plateau after approximately 6 months. Changing from one weight-loss diet to another at the time of the plateau could instigate renewed weight loss. Therefore, our secondary analysis aimed to assess trajectory of weight loss in a 12-month, randomized, cross-over study. Forty-two adults were randomized to eat a healthy low-fat or healthy low-carbohydrate diet for 6 months then switched to the opposite diet for an additional 6 months. Regardless of diet assignment, participants experienced rapid initial weight loss, which slowed between 3 to 6 months. After switching diets at 6 months, weight modestly decreased until 9 months, but at a rate slower than the initial 3 months and slower than the rate from 3 to 6 months. This suggests that the weight loss plateau typically seen at 6 months is physiological and cannot be overcome by simply switching to a different weight-loss diet.

Postoperative hyperglycemia in diabetic patients is a widely known risk factor for postoperative infectious complications (PICs) after esophagectomy; however, the significance of glycemic control in non-diabetic patients is less clear. In diabetic patients, early postoperative management of esophagectomy favors low-carbohydrate enteral nutrition (EN) over standard EN to suppress the risk of glycemic spike. Our single-center, randomized phase II trial seeks to test the hypothesis that low-carbohydrate EN can suppress hyperglycemia in non-diabetic patients who undergo esophagectomy. Herewith we present the study protocol. A total of 50 patients will be enrolled and randomly assigned (1:1 ratio) to standard or low-carbohydrate EN. Randomization will be stratified by operation time (≥560 vs. < 560 min) and HbA1c (6.0-6.4% vs. < 6.0%). Both EN formula will be fed according to the following protocol: 400 mL/24 h on postoperative day (POD)-1; 800 mL on POD-2; 1200 mL on POD-3 and 1600 mL from POD-4 to POD-8. On POD-9, oral food intake will be initiated. A continuous glucose monitoring (CGM) device will be used to monitor blood glucose levels from POD-1 to -8. The primary outcome is the mean time-in-range (TIR) across the 48 h from POD-1 to -2. TIR is defined as the percentage-time that blood glucose remains within the targeted range of 70-180 mg/dL. The primary analysis will calculate the least squares mean difference in TIR over the 48 h (POD-1 to -2) between the two groups, with p-values calculated to test the null hypothesis that the mean difference between the groups is zero. The secondary outcomes will be as follows: 1) the incidence of PICs and/or other adverse events within 30 days after esophagectomy or during the hospital stay; 2) the number of cases requiring any dose alteration in EN formula during monitoring; 3) the number of cases requiring interventions for hyperglycemia or hypoglycemia; 4) the rates in change of nutritional indicators, such as serum albumin, prealbumin, and total protein levels, during the post-surgical hospital stay (vs. those values on the day of admission); and 5) the following CGM indices in relation to the incidence rate of PICs within 30 days after esophagectomy: the mean values for time-above-range (TAR), area under the curve (AUC), and TIR for each POD or from POD-1 to -8. TAR is defined as the percentage of time of a patient is recorded as having hyperglycemia (>blood glucose level of 180 mg/dL), and is indicative of the frequency and duration of hyperglycemia. AUC, which identifies periods of hyperglycemia and provides a comprehensive picture of glucose variability and control in diabetes management, is defined as the area under the curve over blood glucose level of 180 mg/dL on CGM monitoring. This study is the first to investigate the impact of a low-carbohydrate EN formula on hyperglycemic control during perioperative nutritional management of esophageal cancer. These results will help to outline whether glycemic control should be also considered for non-diabetic patients during hospital care. This trial has been registered in the Japanese Registry of Clinical Trials (jRCTs031240081).

Polyunsaturated fatty acids (PUFA) have been shown to reduce liver fat compared to saturated fat, but effects of a novel “anti-lipogenic” diet replacing carbohydrates with PUFA (LCPUFA) or a low-fat healthy Nordic diet (HND) rich in whole-grains are unknown. The objective of this study was to investigate the effects of these diets, as compared with usual care (UC), on liver fat (primary outcome) and related glycemic and lipid disorders after 12 months of intervention, in individuals with prediabetes or type 2 diabetes (T2D). A three-arm parallel ad libitum randomized trial was completed in December 2022 (NCT04527965). Outcome assessors and care providers were blinded to participants’ diets. Men and women (n=150) with prediabetes or T2D (55%) were randomized in a 1:1:1 allocation ratio, stratified by sex and T2D status, and were assessed at the Uppsala Academic hospital. General linear models were employed to estimate intention-to-treat effects. Liver fat was reduced after the LCPUFA diet (n=54) and the HND (n=51) when compared to UC (n=43); -1.46% (95% CI: -2.42, -0.51)) and -1.76 % (95% CI: -2.96, -0.57), respectively. No difference in liver fat between LCPUFA and HND was observed. Body weight and HbA1c decreased more in the HND versus the other diets, whereas no differences were observed between LCPUFA and UC. LDL-cholesterol was reduced to a similar extent during the HND and LCPUFA diet, compared to UC, whereas only HND reduced triglycerides, inflammation and liver enzymes. In total, n=4 serious adverse events occurred, distributed among groups. An ad libitum mainly plant-based LCPUFA diet and HND similarly reduced liver fat and LDL-cholesterol, compared with UC. Even without intentional energy restriction, the HND further improved body weight, glycemic control, liver biochemistry, triglycerides, and inflammation, suggesting a HND as a clinically feasible diet for the management of T2D and metabolic dysfunction-associated steatotic liver disease (MASLD). Previous short-term clinical trials suggested plant-derived polyunsaturated fatty acids (PUFA) reduced liver fat. Here the authors report in a controlled randomised clinical trial that low-fat Nordic diet and a low-carbohydrate diet rich in polyunsaturated fat lowered liver fat content in individuals with prediabetes or diabetes.