Current Gastroenterology Reports (2022) 24:26–36

https://doi.org/10.1007/s11894-022-00840-x

INFLAMMATORY BOWEL DISEASE (B COHEN, SECTION EDITOR)

Impact of Obesity on Inflammatory Bowel Disease

Nidah Shabbir Khakoo1 · Stephanie Ioannou1 · Nabiha Shabbir Khakoo2 · Shyam Vedantam1 · Michelle Pearlman3

Accepted: 13 January 2022 / Published online: 12 February 2022

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022

Abstract
Purpose of Review This review highlights recent work that evaluates the impact of obesity on inflammatory bowel disease
(IBD) pathogenesis and management.
Recent Findings The impact of obesity on IBD prevalence, clinical course, and management, has been studied and described
more so in recent years. Studies have shown that obesity increases IBD disease activity, leads to longer hospitalization
courses, and increases the likelihood of the development of extraintestinal manifestations. Recent evidence has also suggested
that obese IBD patients have a higher frequency of extended steroid treatment and increased use of antibiotics compared to
non-obese IBD patients.
Summary The effect of obesity on patients with IBD is a topic that has garnered widespread interest in the last decade due to
the increasing prevalence of both diseases. To date however, although there are still many unanswered questions. It is quite
clear that obesity, and more specifically, visceral adiposity, affects numerous IBD-related outcomes in regard to pathogenesis,
extra-intestinal manifestations, response to medical and surgical therapies, hospital length of stay, healthcare-related costs,
and health-related quality of life. Future studies should include larger patient populations and evaluate additional factors
that are altered in those with obesity including the gut microbiome, dietary patterns, and whether weight loss and/or degree
of weight loss impact clinical outcomes.

Keywords Obesity · Crohn’s disease · Ulcerative Colitis · Adipose tissue · Inflammatory bowel disease · Body mass index

Introduction obese adults is rapidly increasing in low- and middle-income

countries [3]. Obesity is associated with a myriad of seri-
The global prevalence of obesity has dramatically increased ous health conditions, including hypertension (HTN), type
over the last 50 years, affecting less than 1% of the world’s II diabetes mellitus (DM), sleep disorders, dementia, cardio-
population in 1975 to nearly 13% in 2016 [1]. In the United vascular diseases, and various malignancies, and is associ-
States, the Centers for Disease Control (CDC) reported over- ated with increased morbidity and mortality [4].
all prevalence increase from 30.5% to 42.4% over the past In parallel with the obesity epidemic, the incidence and
20 years [2]. Once thought to be a disease only affecting prevalence of inflammatory bowel disease (IBD) is also rap-
high-income countries, the prevalence of overweight and idly increasing worldwide. It is hypothesized that this trend
may be at least partly related to changes in dietary, lifestyle,
and environmental factors associated with globalization
This article is part of the Topical Collection on Inflammatory
Bowel Disease [5]. Various additional factors may be implicated in the rise
of IBD, including smoking and early exposure to parasitic
* Michelle Pearlman infections and/or antibiotics [1]. While it is well-established
m.pearlman@med.miami.edu that obesity negatively affects the disease course of other
1
Department of Internal Medicine, Jackson Memorial
autoimmune conditions, the specific interplay between
Hospital/University of Miami, Miami, FL, USA excessive body weight and the pathogenesis and clinical
2
University of Miami Miller School of Medicine, Miami, FL,
progression of IBD has yet to be fully elucidated [6]. In this
USA review, we evaluate and discuss recent data pertaining to
3
Department of Medicine, Division of Digestive and Liver
the epidemiology and pathophysiology of obesity in IBD,
Diseases, University of Miami Miller School of Medicine, its effect on the disease course and management, and the
1120 NW 14th Street, Miami, FL 33136, USA

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Current Gastroenterology Reports (2022) 24:26–36 27

influence obesity has on quality of life in those who suffer BMI, which may not be the optimal measure of total body
with IBD. Key findings from recently published literature composition or distribution of adipose tissue (visceral adi-
are summarized in Table 1. posity); the aforementioned measurements may have more
profound effects than just BMI alone.

Epidemiology

To date, there is a paucity of large-scale studies evaluating Pathophysiology of Obesity in Inflammatory

the prevalence of obesity in those with IBD. Furthermore, Bowel Disease
the available data varies widely because of the heterogeneity
of IBD. However, numerous IBD-related studies over the The role of obesity in the development of IBD involves the
last decade, in both pediatric and adult populations, suggest complex interplay of multiple factors, some of which have
that the current prevalence of overweight and obese IBD yet to be elucidated. An in-depth analysis regarding the vari-
patients ranges from approximately 20–30%, similar to that ous pathogenic mechanisms in obesity that may contribute to
of the general population [5]. In 2009, Steed el al. showed a IBD is beyond the scope of this review; however, a summary
significant increase in the percentage of IBD patients with of the proposed mechanisms is depicted in Fig. 1.
obesity, reporting approximately 52% of their IBD patients Adipose tissue found in both subcutaneous and visceral
as overweight or obese and similar rates of obesity amongst fat can be considered a biologically active organ, composed
those with Crohn’s Disease (CD) and Ulcerative colitis (UC) of complex cells that continuously produce and secrete
at 18% and 17.5%, respectively [16]. factors that lead to a chronic, low-grade state of inflamma-
Whether obesity itself is a risk factor for the development tion [22]. These factors, termed “adipokines,” are known
of IBD is still widely debated. A large prospective study of to regulate metabolic homeostasis and important immune
U.S. women enrolled in the Nurses’ Health Study II demon- functions and include resistin, ghrelin, and leptin – all of
strated that obesity and increased weight gain after the age which contribute to a pro-inflammatory state [5]. The adi-
of 18 were associated with a higher risk of developing CD; pokine known as “adiponectin” is decreased in obesity,
however, no association was identified amongst those with which plays a permissive role in the continued production
UC [17]. In contrast, a prospective study of 300,724 patients of pro-inflammatory molecules [23]. Insulin resistance is
from the EPIC cohort (European Prospective Investigation promoted by the interaction of tumor-necrosis-factor-alpha
into Cancer and Nutrition) reported that obesity had no influ- (TNF-ɑ) and insulin receptors, which induces oxidative
ence on the development of CD or UC [18]. stress via increased production of free radicals [23]. Addi-
The rise in childhood obesity has closely mirrored the tionally, obesity is known to lead to alterations in the com-
trends seen in the adult population over the past decade. position of the intestinal microbiome, contributing to dys-
Previously, children with IBD were often described as being biosis [1]. Further, adipose tissue may affect the production
malnourished and/or underweight. However, this association of zonulin, a key mediator of intercellular tight junctions,
is becoming less common as there are increasing numbers and alter other components of intercellular tight junctions
of pediatric patients with IBD who are overweight or obese within the intestinal mucosa, which enhances the produc-
[19]. In a 2012 study of 1,598 children across the United tion of inflammatory adipokines, bacterial translocation,
States by Long et al., the overall prevalence of overweight or and T-cell infiltration [22]. These continued insults lead to
obese children was noted to be 20.0% in those with CD and a perpetual state of chronic, low-grade inflammation, which
30.1% amongst those with UC or indeterminate colitis (IC), in turn enhances the production of several pro-inflammatory
35.2% in Hispanics, and 23.1% among non-Hispanics[20]. factors, including interleukins (IL-1, IL-6, IL-8, IL-10),
Similar to the findings from the Nurses’ Health Study II cytokines and cytokine-related proteins (Interferon-gamma
from 1989 which focused on adult IBD patients, Jensen et al. [IFN-γ], TNF-ɑ), chemokines (monocyte chemoattractant
demonstrated a positive association between risk of CD and protein [MCP-1], macrophage inflammatory protein 1 [MIP-
BMI in those under the age of 30. Interestingly, the study 1], macrophage migration inhibitor factor [MIF]), acute
also observed that being underweight in childhood was a phase reactants (C-reactive protein), and the upregulation of
risk factor for the development of UC later in life [17, 21]. pro-inflammatory signaling pathways (nuclear factor kappa-
Overall, there is a lack of recent and robust epidemiologi- light-chain-enhancer of activated B cells [NF-κB]) [22, 24].
cal data on the prevalence of obesity in IBD in both children Together, this results in the continued production of pro-
and adults. Many of the studies available are cross-sectional, inflammatory factors, facilitating the development of IBD
which often poses a significant challenge when trying to [22, 23]. Whether obesity influences the disease phenotype
establish causality. Furthermore, many of the studies define (i.e., CD versus UC) remains unclear and is an area under
underweight, normal weight, overweight and obese based on active investigation.

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Table 1  Summary of key literature findings regarding the effect of obesity on the clinical course, medical and surgical options, and quality of life in patients with IBD [7–15]
Authors Year Study design Population characteristics marker of Outcomes/Key Findings
obesity

13
Obesity and the clinical course of IBD Greuter et al 2020 Retrospective 3075 IBD patients BMI ≥ 30 kg/m2 Obese CD patients had significantly elevated
-11% were obese CDAI and were less likely to be in remis-
sion based on CDAI < 100 and fecal
calprotectin < 100 ug/g
Nguyen et al 2019 Retrospective 10,256 IBD patients Based on their ICD-9 code Obese patients spent signifantly longer
-50% were obese on admission (278.00, period of time in the hospital compared
278.01, or V85.30-V85.44) to non-obese patients, and had higher
hospitalization-related costs
Obesity and IBD medical therapies Losurdo et al 2020 Case–control 807 IBD patients—438 with CD, 369 BMI > 30 kg/m2 The frequency of extended systemic steroid
with UC treatment and use of antibotics were
-6.9% were obese (BMI ≥ 30 kg/m2) among greater in obese patients compared to non-
those with IBD obese patients with IBD. No difference
378 patients without IBD was found between groups in the use of
-7.9% were obese (BMI ≥ 30 kg/m2) among biologics, mesalazine, or thiopurines
those without IBD
Allin et al 2021 Prospective cohort 3,917,843 IBD patients—15,347 had a Not specified Bariatric surgery was associated with
bariatric surgery increased risk for development of new-
onset CD, but not for risk of new-onset UC
McKenna et al 2020 Retrospective 31 IBD patients – 10 with CD, 20 with Not specified Bariatric surgery was safe in IBD patients
UC, 1 with IC with no observed increase in infectious
complications related to patients’ IBD.
Bariatic surgery also led to sustained
weight loss at 6, 12, and 24 months, and
found no IBD flares requiring surgery dur-
ing the follow up period
Braga Neto et al 2020 Case–control 47 IBD patients – 12 with CD, 13 with UC Not specified Compared IBD patients undergoing bariatric
surgery to matched controls (IBD patients
not undergoing bariatric surgery), and
found that cases were less likely to require
rescue corticosteroid usage and less likely
to require IBD-related surgeries
Heshmati et al 2019 Retrospective 54 IBD patients – 19 (8 with CD, 11 with Not specified There was a significant difference in the
UC) patients had RYGB, 35 (23 with proportion of patients with worsened
CD, 12 with UC) had SG CD (through increased IBD medication
requirements) after RYGB and a greater
rate of surgical complications after RYGB
compared to SG
McKenna et al 2019 Retrospective 758 CD patients who underwent ileoco- BMI ≥ 30 kg/m2 Obese CD patients who had undergone
lonic resection ileocolonic resections were more likely
-17% were obese to require conversion to open surgery and
to have superficial surgical site infection,
with obesity being an independent risk
factor for superficial surgical site infections
Current Gastroenterology Reports (2022) 24:26–36
 Current Gastroenterology Reports (2022) 24:26–36 29

Adipose tissue comes in a variety of biologically active

associated with higher anxiety, depression,

patients were also found to have worsened

depression, fatigue, pain, and social func-
scores in UC and CD patients at baseline.
fatigue, pain, and inferior social function
forms, and is present in a unique form called “creeping fat,”

On longitudinal assessment, obese CD

Obesity was found to be independently
which is defined as pathological fat hyperplasia that is limited
to areas of inflamed intestine in those with IBD [1]. Creeping
fat is primarily observed in CD and is thought to be more
immunologically active than other forms of adipose tissue
[25]. Moreover, the extent of creeping fat correlates strongly
with the severity of microscopic inflammation and degree of
immune cell infiltration, fibrosis, and stricture formation [22,
25]. In addition, the expression of adipokines is increased in
Findings

tion

the hypertrophied mesenteric fat of patients with CD, further

contributing to a state of perpetual inflammation [1].
7,296 IBD patients—4,748 with CD, 2,548 BMI 30–34.9 kg/m2 obesity
class I, 35–39.9 kg/m2

Effect of Obesity on Inflammatory Bowel

obesity class II

Disease Course
Outcomes/Key

Obesity may be associated with an increased risk of IBD

severity and IBD-related complications. However, more
recent studies show conflicting results and may suggest that
conditions that are commonly associated with obesity, such
Population characteristics marker of

as metabolic syndrome, may have a more significant impact

-19.5% of CD patients were obese
-20.3% of UC patients were obese

than just the presence of obesity itself.

Multiple studies identify an inverse relationship between
disease activity in CD and BMI. One study found that
patients with CD with a BMI > 25 kg/m2 had less extensive
disease activity than those with BMI < 25 kg/m2. In addition,
patients with a lower BMI were more likely to be described
with UC
obesity

as having active disease, compared to those with a higher

BMI. No correlation was found between BMI and duration
of disease, perianal disease, endoscopic severity, history of
small bowel resection, or use of biologics [26]. Similarly,
Cross-sectional

one cross-sectional study found that patients with BMI ≥ 30

Study design

had lower risk of penetrating disease compared to those with

a BMI < 25 (OR = 0.56, 95% CI 0.31–0.99), and no associa-
tion was found between BMI and risk of perianal disease,
2019
Year

stricturing disease, or IBD-related surgery [27]. Several

studies have investigated whether colonic involvement in
CD may be associated with obesity (particularly BMI ≥ 35),
however results have been inconsistent [27–31]. On the con-
Jain et al

trary, a recent Swiss study used the Crohn’s Disease Activ-

Authors

ity Index (CDAI) to objectively measure disease activity

and showed that obese patients with CD had significantly
Obesity and quality of life in IBD patients

elevated CDAI scores [7].

Among those with UC, recent studies suggest that
obesity has an inverse relationship with disease severity
[7, 8]. One study demonstrated that overweight patients
were found to have less active disease compared to normal
Table 1  (continued)

weight patients and a lower prevalence of pancolitis in

obese patients compared to those with a normal BMI. This
inverse relationship suggests that increased BMI may actu-
ally exert a protective effect on disease severity [31]. An
alternative hypothesis may be that active disease prevents

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the development of obesity secondary to malabsorption, The Effect of Obesity on IBD Management
diarrhea and decreased oral intake, thus lowering the
apparent rate of obesity in those with severe IBD, rather Medical Management
than obesity itself being protective.
In studies investigating hospitalization of patients with In general, pharmacokinetic studies have found that in
IBD, data suggests an association between increasing BMI patients treated with biologics, high body weight is a risk
and more prolonged hospital length of stay (LOS) and factor for increased drug clearance, shortened half-life, and
healthcare costs. One study found that obese patients spent low trough drug concentrations as a result of rapid proteoly-
a median of eight days in the hospital per year, compared sis and a phenomenon referred to as “TNF sink,” whereby
to five days in non-obese patients (p < 0.01), and had higher increased levels of adipose-secreted TNF sequester anti-TNF
hospitalization-related costs [8]. Similarly, Singh et al. agents [40–42].
demonstrated that obese adults with CD and UC had pro- Overall, data suggest that patients treated with anti-TNF
longed hospital LOS compared to non-obese patients, and agents, such as Infliximab (IFX) or Adalimumab (ADA),
those with UC had higher rates of surgery and hospital LOS require dose escalation with increasing BMI. One study of
greater than seven days [32]. There is some evidence to sug- 124 IBD patients treated with IFX found that obese patients
gest that certain comorbid conditions, particularly metabolic were three to nine times more likely to have an IBD flare
syndrome, play a key role in hospital LOS in obese patients and require dose escalation when compared to patients with
with IBD as well [33]. a normal weight [5]. Another study found that BMI was the
Some researchers have hypothesized that obesity may only independent predictor for need for dose escalation in
influence systemic inflammatory markers (i.e. erythrocyte those with CD receiving ADA [43].
sedimentation rate (ESR) and/or CRP), but whether this is Other factors that may influence response to therapy are
a true reflection of disease activity is unclear [26, 34]. In route of administration and weight-based dosing. Observa-
regards to the development of extra-intestinal manifesta- tional studies suggest that patients with CD who are treated
tions (EIM), studies suggest that those with a greater BMI with IFX have lower rates of IBD-related hospitalizations
are more likely to have EIM such as arthralgias, erythema and abdominal surgeries compared to those treated with
nodosum, and inflammatory arthritis (p = 0.005) [26]. ADA or Certolizumab [32, 44]. One explanation is the vari-
Regarding disease onset, progression, and involvement, ation in dosing and route of administration. IFX uses weight-
a case control study consisting of 807 patients published in based dosing and is administered intravenously, whereas
2020 by Losurdo et al. compared obese versus non-obese other biologics (such as ADA) are administered subcuta-
IBD patients and demonstrated that age of IBD onset was neously in a fixed-dose manner. Similar findings have also
earlier in obese patients; however, no difference was found been demonstrated in non-IBD autoimmune conditions, such
in regard to disease location as defined by the Montreal clas- as psoriasis [45]. Multiple studies have found that ADA is
sification (p = 0.004) [9]. associated with need for dose escalation and lower trough
levels in obese IBD patients, a finding that is not seen in
those treated with IFX [46, 47]. Possible hypotheses include
The Effect of Visceral Adiposity on IBD lower likelihood of obese patients receiving appropriately
dosed therapy in a fixed-dosing regimen or poor absorp-
While obesity is measured by overall BMI, visceral adipos- tion of medication via subcutaneous routes of administration
ity is measured by the ratio of visceral adipose tissue to compared with intravenous route. These findings however
subcutaneous adipose tissue on cross-sectional imaging. are not consistent throughout the literature. A retrospective
Data suggest that visceral adiposity is associated with an cohort study evaluating biologic-treated UC patients found
increased risk of complications and disease recurrence in that regardless of whether patients were on weight-based
those with CD after surgical resection [35, 36]. Addition- or fixed-dose regimens, each 1 kg/m2 increase in BMI was
ally, further studies have found higher rates of post-operative associated with 4% increase in the risk of treatment failure
complications in obese patients with CD when defining obe- and 8% increase in risk of surgery and/or hospitalization
sity by volumetric analysis rather than BMI stratification [41]. However, another study found the opposite result,
[37–39]. Therefore, consideration of visceral adiposity or with no overall association between time to loss of response
central obesity, rather than BMI-based criteria, may be more (LOR) and increasing weight among patients treated with
accurate when evaluating the effects of obesity and meta- anti-TNF agents [48].
bolic syndrome on IBD-specific outcomes. Dreesen et al. retrospectively analyzed 179 patients with
IBD treated with an integrin blocker, Vedolizumab (VDZ),
another fixed-dose biologic. The study demonstrated that

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Current Gastroenterology Reports (2022) 24:26–36 31

Fig. 1  Schematic displaying pathogenic factors that contribute to tributing to dysbiosis [1]. Further, adipose tissue may alter compo-
the intestinal inflammatory response in inflammatory bowel disease. nents of the intercellular tight junctions within the intestinal mucosa,
The role of fat in obesity is hypothesized to involve the interaction which enhances the production of inflammatory adipokines, bacte-
of multiple complex mechanisms. Adipose tissue found in both sub- rial translocation, and T-cell infiltration [22]. These continued insults
cutaneous and visceral fat can be considered a biologically active lead to a state of low-grade inflammation, which in turn enhances the
organ, as it continuously secretes and produces factors that lead to a production of several factors including interleukins (IL-1, IL-6, IL-8,
chronic, low-grade state of inflammation [22]. These factors, termed IL-10), cytokines and cytokine-related proteins (Interferon-gamma
‘adipokines,’ include resistin, ghrelin, and leptin—all of which con- [IFN-γ], TNF-ɑ), chemokines (monocyte chemoattractant protein
tribute to a pro-inflammatory state [5]. The adipokine, ‘adiponectin,’ [MCP-1], macrophage inflammatory protein 1 [MIP-1], macrophage
is decreased in obesity, which plays a permissive role in the continued migration inhibitor factor [MIF]), acute phase reactants (C-reactive
production of pro-inflammatory molecules [23]. Insulin resistance is protein), and the upregulation of pro-inflammatory signaling path-
promoted by the interaction of tumor-necrosis-factor-alpha (TNF-ɑ) ways (nuclear factor kappa-light-chain-enhancer of activated B cells
and insulin receptors, which leads to increased free radical produc- [NF-κB]) [22, 24]. Together, this results in the continued production
tion and oxidative stress [23]. Additionally, obesity is known to lead of pro-inflammatory factors, facilitating the development of IBD [22,
to alterations in the composition of the intestinal microbiome, con- 23]. Figure shown was created based on several references

having a higher BMI during VDZ therapy initiation was Surgical Management
associated with lower trough concentrations over a 30-week
period and a lower probability of mucosal healing (p < 0.05) Multiple studies in recent years have evaluated the effect
[49]. of obesity on the need for IBD-related surgeries, opera-
Lastly, one study evaluated the effect of obesity on treat- tive characteristics, and post-operative complications;
ment with non-biologic agents and found that frequency of however, findings are inconsistent.
extended systemic steroid treatment (p = 0.02) and use of Data suggest that overweight patients require surgery
antibiotics (p = 0.05) were greater in those with obesity [9]. significantly earlier compared to underweight patients.
Overall, there appear to be multiple hypotheses to suggest One study found that for patients with a BMI > 25 kg/
that response to medical treatment for those with IBD is m 2, the average time to first IBD-related surgery was
altered in those who have obesity and may have future impli- 24 months, compared to 252 months for patients with
cations in deciding which therapies should be considered BMI < 18.5 kg/m2 (p = 0.043) [50]. However, the data are
first-line in this patient population. equivocal on the association between obesity and the life-
time need for surgery [27, 28]. A study of IBD patients
in Scotland found an increased need for surgery among

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overweight and obese patients with UC compared to non- IBD to require rescue corticosteroid usage or IBD-related
obese patients; however, the same study found the opposite surgeries, despite a higher BMI after bariatric surgery com-
results in those with CD, with increased frequency of sur- pared to controls who had not undergone bariatric surgery
gery performed in the normal-weight group [16]. [10]. Another study comparing Roux-en-Y gastric bypass
For ileal pouch-anal anastomosis (IPAA), one study (RYGB) to sleeve gastrectomy (SG) found that RYGB is
looked at short- and long-term post-operative compli- associated with worsened CD (p = 0.016) and a greater rate
cations in 909 UC patients. While no associations were of surgical complications (p = 0.02) compared to SG, sug-
observed for 1-stage IPAA, obese patients receiving 2- or gesting that SG may be a safer procedure in obese patients
3-stage IPAA had greater estimated blood loss (p = 0.005 with CD [11].
vs. p < 0.0001), longer operative times (p = 0.02 vs. Recently, there has been some data to suggest an
p = 0.0002) and were less likely to receive laparoscopic increased risk of new-onset IBD following bariatric surgery.
surgery (p < 0.0001 for 2-stage IPAA vs. p = 0.03 for Allin et al. followed a cohort of over three million individu-
3-stage IPAA). They also found that obese patients were als and found an association between new-onset CD and
more likely to have longer hospital LOS after 2-stage those who had undergone bariatric surgery, but was not seen
IPAA (p = 0.009) and an increased risk of superficial surgi- in those with UC [12].
cal site infections (p = 0.003), however there were no sig-
nificant differences in long-term clinical outcomes (e.g.,
incontinence, frequency of bowel movements, pad usage, Obesity and Quality of Life
and pouchitis) in post-operative obese patients compared
to non-obese patients [51]. While most IBD-related clinical studies focus on disease
Similarly, another study by the same group found that outcomes and efficacy of various treatments, the Food and
obesity was an independent risk factor in patients with CD Drug Administration (FDA) has recently advocated for the
who underwent ileocolonic resection for conversion to an inclusion of health-related quality of life (HRQoL) measures
open surgery, and was associated with increased develop- in drug development clinical trials [53, 54]. HRQoL incor-
ment of superficial surgical site infections [51]. porates several domains, including patient perceptions of
Other studies have found that measures of obesity other physical and psychosocial functioning, mental health, and
than BMI (i.e. calculated visceral/subcutaneous ratio) general health [55]. Although these aspects provide mean-
showed an increased correlation with post-operative com- ingful insight to a patient’s life beyond traditional clinical
plications in those with CD undergoing an elective ileo- settings, the subjective nature of HRQoL is arguably a chal-
colectomy and a statistically significant association between lenge to interpret, as patients with the same objective health
higher visceral adiposity, operative and post-operative com- status can report dissimilar HRQoL due to differences in
plications, and increased risk of recurrence of CD after sur- coping abilities and expectations [56, 57].
gical resection [36, 38, 39]. In IBD, HRQoL is generally assessed by patient-reported
However, other studies suggest there is no difference outcomes obtained via the Short-Form 36 questionnaire or
in operative risk in obese patients compared to non-obese disease-specific scales, such as the Inflammatory Bowel
patients with IBD. One study analyzed the general periop- Disease Questionnaire (IBDQ) [53]. These surveys inquire
erative and postoperative surgical outcomes in underweight, about distress, health anxiety, perceived stress, and the need
normal weight, overweight, and obese patients with IBD for social support. While it is well-established that disease
who underwent intestinal surgery and found no difference symptoms play an important role in HRQoL, even asympto-
in laparoscopic conversion to open, estimated blood loss, matic patients report lower HRQoL due to fear of pain and
intraoperative complications, or median operative time. pain-specific catastrophizing [58]. In light of these findings,
Similarly, no difference was found in 30-day postoperative there have been more concerted attempts to bridge the gap
complications between the groups, including total complica- between patient- and physician-specific experiences in man-
tions, wound infections, or anastomotic leaks [52]. aging patients with IBD. A 2020 meta-synthesis reported
Given the reported complications associated with severe three essential themes that negatively impact the psychoso-
obesity in IBD, one potential solution is offering bariatric cial well-being of IBD patients: 1) unpredictability of IBD,
surgery. Studies examining the safety of bariatric surgery in 2) the emotional turmoil of living with IBD, and 3) the dif-
obese patients with IBD have found bariatric surgery to be ficulty of maintaining a normal life while managing IBD
safe overall. One study observed sustained weight loss at [59]. Patients also expressed a desire for increased physician
6, 12, and 24 months, with no IBD flares requiring surgery training to shorten the path to diagnosis and greater integra-
during the follow-up period (mean 2.7 years) [51]. Another tion of mental health support [60].
case–control study found that IBD patients undergoing bari- Obesity, independent of IBD, is strongly correlated with
atric surgery were less likely than matched controls with decreased HRQoL [61]. There are, however, IBD-related

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HRQoL risk factors that overlap with those of obesity Thrombotic events are another disease process that is
including female gender, lower socioeconomic status, and seen more commonly in those with obesity and IBD. Obe-
ethnicity [62]. Of note, there should be increased aware- sity causes chronic inflammation (via adipokines, cytokines,
ness of female IBD and obese patients’ HRQoL, as studies tissue factor, and macrophages), impaired fibrinolysis (via
suggest females are more likely to report concerns related increased plasminogen activator inhibitor-1 [PAI-1]), and
to attractiveness and body image and worries about being venous stasis. Similarly, IBD causes episodic acute on
treated differently because of their illness [63, 64]. Fur- chronic inflammation, impaired fibrinolysis (similarly via
thermore, obesity has been associated with higher anxiety, increased PAI-1 and decreased expression of tissue plasmi-
depression, fatigue and pain, as well as inferior social func- nogen activator [t-PA]), and malnutrition. The frequent use
tion scores compared with non-obese patients with IBD of corticosteroids in IBD may exacerbate this prothrombotic
[13]. Obese patients with IBD also have a higher annual state by increasing fibrinogen and decreasing t-PA [71, 72].
burden and cost of hospitalization compared with non-obese There are currently no therapeutic approaches for pre-
patients, further exacerbating financial stressors [8]. venting or managing thrombosis in obese patients, other
It is difficult to pinpoint a singular method to improve than weight loss [73]. However, a consensus statement by
HRQoL in those with IBD. A 2015 Cochrane review found the Canadian Association of Gastroenterology published
that Infliximab and Vedolizumab improve HRQoL in UC guidelines on anticoagulation therapy after a venous throm-
induction and maintenance therapy, respectively [65]. How- boembolic event [74]. The guidelines suggest anticoagulant
ever, a more recent meta-analysis demonstrated that the prophylaxis in patients with active IBD and minor gastro-
placebo effect improves HRQoL in IBD patients, possibly intestinal bleeding in those undergoing major surgery [75].
related to expectations regarding the perceived increased Second, if there is a history of venous thrombotic event(s)
effectiveness of biologics and intravenous/subcutaneous during a previous flare, then preventative anticoagulation is
medications compared to oral treatments [66]. A recent recommended during subsequent flares.
study found that psychological intervention led to reductions Infertility is another common problem in those with both
in IBD symptoms and depression scores and that a person- obesity and IBD. In obesity, this is thought to be related to
alized exercise program improved fatigue and HRQoL in maladaptive changes in the hypothalamic-pituitary-ovarian
those with quiescent disease [67]. Therefore, it is reasonable (HPO) axis, menstrual cycle disturbance, and oligo-/anovu-
to suggest that a multimodal approach is required to miti- lation. Furthermore, obese women are at an increased risk of
gate HRQoL issues in these patients. Ultimately, HRQoL maternal and perinatal complications [76]. Pregnant women
for obese patients with IBD is an important factor that is with IBD are at an increased risk of complications as well,
often underappreciated, and clinicians should consider a including venous thromboembolism, need for blood transfu-
more holistic approach towards addressing this particular sions, antepartum hemorrhage, and need for cesarean section
patient population. [1, 77]. There is an incomplete understanding of the exact
mechanisms that underscore these associations, but they are
thought to be related to the improper balance of estrogen and
TNF signaling [78].
IBD, Obesity, and Other Comorbid
Conditions
Conclusions and Future Directions
The combined impact of obesity and IBD on other comor-
bidities has not been widely explored. While both obesity The prevalence of both obesity and IBD is on the rise and
and IBD are pro-inflammatory conditions, there is a relative presents numerous therapeutic challenges in the manage-
dearth of information regarding their combined effect on ment of patients with IBD. Studies have shown conflict-
other disease processes such as colorectal cancer (CRC), ing results, but seem to suggest that obesity increases IBD
thrombotic events and infertility, among others. disease activity, leads to longer hospital length of stay,
Studies suggest that both obesity and IBD are associated increases the likelihood of extraintestinal manifestations,
with an increased risk of the development of CRC (HR 1.16 and is associated with a higher frequency of prolonged ster-
and 1.88 respectively), although the risk varies depending on oid treatment and increased use of antibiotics compared to
the IBD duration, intestinal involvement, and disease activ- non-obese IBD patients. To date, although there are still
ity [68–70]. Current CRC screening guidelines do not take many unanswered questions, it is quite clear that obesity,
into account obesity as a risk factor, however this should and more specifically, visceral adiposity, affects numerous
be considered in future screening guidelines as more data IBD-related outcomes in regard to pathogenesis, extra-intes-
become available. tinal manifestations, response to medical and surgery thera-
pies, hospital length of stay, healthcare-related costs, and

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34 Current Gastroenterology Reports (2022) 24:26–36

health-related quality of life concerns. Using BMI to define outcome in inflammatory bowel disease: results from the Swiss
overweight and classes of obesity also presents a challenge inflammatory bowel disease cohort. United Eur Gastroenterol J.
2020;8:1196–207.
because it does not account for those with visceral adipos- 8. Nguyen NH, Ohno-Machado L, Sandborn WJ, Singh S. Obesity
ity, which is often associated with metabolic syndrome, and is independently associated with higher annual burden and costs
seems to have a more significant impact on systemic inflam- of hospitalization in patients with inflammatory bowel diseases.
mation, particularly in those with IBD. Clin Gastroenterol Hepatol. 2019;17:709-718.e7. https://​doi.​org/​
10.​1016/j.​cgh.​2018.​07.​004.
Future directions for further study include investigating 9. Losurdo G, La Fortezza RF, Iannone A, Contaldo A, Barone M,
large cohorts of pediatric patients and young adults using Ierardi E, et al. Prevalence and associated factors of obesity in
various anthropometric measurements to determine a more inflammatory bowel disease: a case-control study. World J Gas-
precise contribution of obesity to IBD pathogenesis, pro- troenterol. 2020;26:7528–37.
10. Braga Neto MB, Gregory MH, Ramos GP, Bazerbachi F, Bruin-
spective studies in both pediatrics and adults, and a more ing DH, Abu Dayyeh BK, et al. Impact of bariatric surgery on the
pronounced focus on risk factor mitigation and weight loss long-term disease course of inflammatory bowel disease. Inflamm
to determine if, and what degree of weight loss is required Bowel Dis. 2020;26:1089–97.
to improve disease activity, response to treatment, reduce 11. Heshmati K, Lo T, Tavakkoli A, Sheu E. Short-Term Outcomes
of Inflammatory Bowel Disease after Roux-en-Y Gastric Bypass
risk of complications, and improve health-related quality vs Sleeve Gastrectomy. J Am Coll Surg. 2019;228:893-901.e1.
of life in patients with IBD and obesity. Further, practice https://​doi.​org/​10.​1016/j.​jamco​llsurg.​2019.​01.​021.
guidelines to help clinicians develop personalized nutrition 12. Allin KH, Jacobsen RK, Ungaro RC, Colombel J-F, Egeberg
plans for patients based on their food preferences and weight A, Villumsen M, et al. Bariatric surgery and risk of new-onset
inflammatory bowel disease: a nationwide cohort study. J Crohns
goals to prioritize foods rich in antioxidants and minimize Colitis; 2021.
pro-inflammatory foods may be helpful to help IBD patients 13. Jain A, Nguyen NH, Proudfoot JA, Martin CF, Sandborn WJ,
maintain lean body mass and reduce the risk of future IBD Kappelman MD, et al. Impact of obesity on disease activity and
flares. patient-reported outcomes measurement information system
(PROMIS) in inflammatory bowel diseases. Am J Gastroenterol.
2019;114:630–9.
14. McKenna NP, Habermann EB, Sada A, Kellogg TA, McKenzie TJ.
Declarations Is bariatric surgery safe and effective in patients with inflamma-
tory bowel disease? Obes Surg Obesity Surgery. 2020;30:882–8.
Financial Disclosures None. 15. McKenna NP, Habermann EB, Zielinski MD, Lightner AL,
Mathis KL. Body mass index: Implications on disease severity
and postoperative complications in patients with Crohn’s dis-
Conflicts of Interest The authors declare no competing interests. ease undergoing abdominal surgery. Surgery (United States).
2019;166:703–8. https://​doi.​org/​10.​1016/j.​surg.​2019.​04.​038.
Human and Animal Rights and Informed Consent This article does not 16. Steed H, Walsh S, Reynolds N. A brief report of the epidemiol-
contain any studies with human or animal subjects performed by any ogy of obesity in the inflammatory bowel disease population of
of the authors. Tayside. Scotland Obes Facts. 2009;2:370–2.
17. Khalili H, Ananthakrishnan AN, Konijeti GG, Higuchi LM, Fuchs
CS, Richter JM, et al. Measures of obesity and risk of Crohn’s
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