Obesity and novel management of inflammatory bowel disease

Table 2 Impact of obesity treatment on inflammatory bowel disease outcomes

Interventions		Study design	Key finding	Ref.
Lifestyle and dietary interventions	Diet: No data on the effects of overall calorie intake or supervised dietary weight loss on outcomes in IBD patients	Retrospective study: (1) Impact of mediterranean diet on the liver steatosis, clinical disease activity, and QoL in IBD patients (n = 142); (2) 84 UC, 58 CD; and (3) BMI: Collected at study baseline and after 6 mo	Diet-adherent CD and UC improved BMI (UC: -0.42, P = 0.002; CD: -0.48, P = 0.032) and waist circumference (UC: -1.25 cm, P = 0.037; CD: -1.37 cm, P = 0.041). The number of patients affected by liver steatosis of any grade was significantly reduced in both groups after mediterranean diet intervention (UC: 36.9% vs 21.4%, P = 0.0016; CD: 46.6% vs 31.0%, P < 0.001). Mediterranean diet improved QoL in both UC and CD	Chiccoet al[72], 2021
	Exercise: (1) Anti-inflammatory effects through a variety of mechanisms, including reducing visceral fat, reducing the secretion of inflammatory adipokines, and reducing stress-induced intestinal barrier dysfunction; and (2) Experts have recommended a prescription of exercise for IBD patients that consists of walking 20-30 min at 60% of maximal heart rate 3 d per week along with resistance training 2-3 times per week for its impact on bone mineral density[102], however this has not been tested prospectively	Prospective study: IBD patients with mild active disease or in remission (n = 32)	IBD patients performed low-intensity walking at an interval of 3 times per week for a duration of 3 mo. IBD patients who exercise have improved sense of well-being and QoL	Ng et al[103], 2007
		30 patients with moderate-to-mild CD. Randomized to moderate-intensity running 3 × weekly for 10 wk vs usual care	No significant difference in total IBDQ scores, IBDQ social subscores did improve in intervention group (P = 0.023). No disease exacerbation	Klare et al[104], 2015
		Prospective study: Using the Crohn’s and Colitis Foundation of America Partners Internet-based cohort of IBD patients (n = 1857); 549 UC, 1308 CD	Reduced risk of CD exacerbation (RR = 0.72, 95%CI: 0.55-0.94), reduced risk of UC exacerbation (RR = 0.78, 95%CI: 0.54-1.13), with higher levels of exercise	Jones et al[74], 2015
Pharmacologic treatment: BMI of 30 kg/m2 or a BMI of 27 kg/m2 with obesity-related diseases (e.g., hypertension, type 2 diabetes mellitus, and sleep apnea)	Orlistat: (1) By inhibiting gastric and pancreatic lipases, reducing absorption of monoaclglycerides and free fatty acids; and (2) Should be avoided in IBD patients because of the mechanism of action and common side effect	No data on the effect of Orlistat on outcomes in IBD patients
	Liraglutide: Glucagon-like peptide-1 receptor agonist also known as incretin mimetics	Case report: CD patient with type 2 diabetes and active CD	Switching from insulin to liraglutide improved glycemic control and the QoL scores	Kuwata et al[76], 2014
		A nationwide cohort study using Danish registries: Patients with IBD and type 2 diabetes (n = 3751)	A lower risk of adverse clinical events (a composite of the need for oral corticosteroid treatment, need for TNF-α-inhibitor treatment, IBD-related hospitalization, or IBD-related major surgery) amongst patients treated with GLP-1 based therapies compared with treatment with other antidiabetic therapies (adjusted IRR = 0.52, 95%CI: 0.42-0.65)	Villumsen et al[77], 2021
	Naltrexone/bupropion: Naltrexone and bupropion alone may have anti-inflammatory properties	Uncontrolled studies of IBD patients not in remission (n = 47): Low-dose naltrexone for 12 wk	Low dose naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients	Lie et al[78], 2018
		Retrospective study of IBD patients who had received low-dose naltrexone (n = 582)	Initiation of low-dose naltrexone in IBD was followed by reduced dispensing of several drugs considered essential in the treatment of IBD	Raknes et al[79], 2018
	Phentermine/topiramate: (1) A highly efficacious oral weight-loss agent, which acts centrally to suppress appetite and increase satiety; and (2) Early experimental data on topiramate suggested that it could significantly reduce colonic tissue damage in animal models of IBD	Large retrospective cohort study using United States administrative claims data (n = 1731): Compared new users of topiramate with users of other anticonvulsant/anti-migraine medications	Topiramate use was not associated with markers of IBD flares including steroid prescriptions (HR = 1.14, 95%CI: 0.74-1.73), initiation of biologic agents (HR = 0.93, 95%CI: 0.39-2.19), abdominal surgery (HR = 1.04, 95%CI: 0.17-6.41), or hospitalization (HR = 0.86, 95%CI: 0.62-1.19)	Crocket et al[83], 2014
Bariatric endoscopic applications	Intragastric balloon: Weight loss achieved through endoscopic bariatric interventions might achieve the same effect on outcomes in IBD as in other autoimmune diseases, but has not been studied	Case report of UC patient	UC worsened after insertion of an intragastric balloon for the treatment of obesity	Manguso et al[88], 2008
Bariatric surgery: BMI ≥ 40 kg/m2 or 35-39.9 kg/m2 with obesity-related comorbidities and previously failed to achieve adequate weight reduction with non-surgical interventions	Bariatric surgery: (1) Several studies have demonstrated that bariatric surgery is likely feasible, safe, and effective weight loss stratege, that may lead to improved outcomes of IBD patients; and (2) No RCTs or prospective studies were found that compared the different bariatric procedures in patients with IBD	Case-control study of 85 IBD patients, matched to non-IBD patients with BS (n = 85): (1) 20 UC, 64 CD, 1 unclassified IBD; (2) BMI 41.6 ± 5.9 kg/m2; and (3) 3 RYGB/73 SG/12 LAGB	Bariatric surgery is a safe and effective procedure in obese IBD patients: (1) At a mean follow-up of 34 mo, mean weight was 88.6 ± 22.4 kg; (2) Complications: 8 (9%); and (3) No difference was observed between cases and controls for postoperative complications (P = 0.31), proportion of weight loss (P = 0.27), or postoperative deficiencies (P = 0.99)	Reenaers et al[93], 2022
		Case-control study of 25 IBD patients who underwent BS, matched to IBD patients who did not undergo BS (n = 47)	IBD patients with weight loss after BS had fewer IBD-related complications compared with matched controls: (1) Median decrease in body mass index after bariatric surgery was 12.2; and (2) Rescue corticosteroid usage and IBD-related surgeries were numerically less common in cases than controls (24% vs 52%, OR = 0.36, 95%CI: 0.08-1.23; 12% vs 28%, OR = 0.2, 95%CI: 0.004-1.79)	Braga Neto et al[95], 2020
		Retrospective review (n = 20): (1) 13 UC, 7 CD; (2) BMI 50.1 ± 9 kg/m2; and (3) 9 SG/7 RYGB/3 AGB/ 1 AGB to RYGB	BS is safe and mitigate IBD: (1) Weight loss: 14.3 ± 5.7 kg/m2 or 58.9% ± 21.1%; (2) Complications: Early 7 (5 Dr, 1 PE, 1 WI), late 5 (2 Pnt, 2 VH, 1 MU), mortality 1 (unrelated); and (3) IBD status after BS: Remit 9, exacerbate 2, no change 9	Aminian et al[91], 2016
		Prospective case-control study (n = 6/101): (1) 1 UC, 5 CD; (2) BMI 40.6 ± 3.74 kg/m2; and (3) 1 Maclean gastroplasty/1 SG + end colostomy/2 SG/2 SG + ileocecal resection	BS is safe and effective and IBD Rx decreasing: (1) Weight loss: 11.45 ± 2.8 kg/m2 or 28.14% ± 6.6%; (2) Complications: Late 1 (1 vomiting/dysphagia); and (3) IBD status after BS: Remit 5, exacerbate 1	Colombo et al[105], 2015
		Prospective study (n = 10): (1) 2 UC, 8 CD; (2) BMI 42.6 ± 5.6 kg/m2; and (3) 9 LSG/1 LAGB	BS is effective and safe: (1) Weight loss: 71.4 ± 5.9 EWL%; (2) Complications: Early 1 (1 SLL) late 4 (4 VitD); and (3) IBD status after BS: Remit 2, exacerbate 3, no change 3, improved 1	Keidar et al[106], 2015
		Retrospective case-control (n = 4): (1) 4 CD; (2) BMI 45 ± 5.3 (40-51) kg/m2; and (3) 4 LSG	SG is safe in CD: (1) Weight loss: 32.8 ± 4.3 kg/m2 or 60.2% ± 13.7% EWL; (2) Complications: Early 1 (1 SLB); and (3) IBD status after BS: Remit 4	Ungar et al[107], 2013
		Retrospective inpatient study (n = 493/15319): (1) 245 UC, 248 CD; (2) BMI 40.6 ± 3.74 kg/m2; and (3) 48% SG, 35% RYGB, 17% LAGB	Complications: 0.4% malnutrition, 0.2% thromboembolism, 12% strictures, 0.6% renal failure; prior-bariatric surgery was associated with decreased IRR for renal failure, under-nutrition, and fistulae formation in morbidly obese IBD patients [(IRR = 0.1; 95%CI: 0.02-0.3; P < 0.001), (IRR = 0.2; 95%CI: 0.05-0.8; P = 0.03), and (IRR = 0.1; 95%CI: 0.2-08; P = 0.03), respectively]	Sharma et al[108], 2018

IBD: Inflammatory bowel disease; QoL: Quality of life; CD: Crohn’s disease; UC: Ulcerative colitis; RR: Risk ratios; IBDQ: Inflammatory bowel disease questionnaire; IRR: Incidence rate ratio; BS: Bariatric surgery; OR: Odds ratio; Dr: Dehydration; EWL: Excess weight loss; LAGB: Laparoscopic adjustable gastric banding; MU: Marginal ulcer; PE: Pulmonary embolism; Pnt: Pancreatitis; Rx: Treatment; SG: Sleeve gastrectomy; SLB: Staple line bleeding; SLL: Staple line leak; VH: Ventral hernia; VitD: Vitamin deficiency; WI: Wound infection; CI: Confidence interval; RCT: Randomized control trial; RYGB: Roux-en-Y gastric bypass.