Clinical impact of body mass index on bactibilia and bacteremia

Obesity is a well-established risk factor for cholesterol gallstone and subsequent cholecystectomy [1‐4]. This is because of the increased cholesterol synthesis or secretion associated with glucose intolerance and insulin resistance [2, 5]. Gallbladder (GB) hypomotility secondary to obesity or autonomic neuropathy has also been proposed as one of the mechanisms [6, 7]. However, the association between obesity and bactibilia or bacteremia, which have been postulated as one of the mechanisms or manifestations of cholecystitis remains unclear. Selecting empirical antibiotics in patients with bactibilia or bacteremia is also important.

The present study aims to provide an association between obesity and bactibilia or bacteremia in patients with acute calculous cholecystitis and to obtain isolated bacterial profiles of bile and blood to help direct empirical therapy.

Bactibilia and bacteremia are serious manifestations of acute cholecystitis and are known to be associated with complications, mortality and prognosis [9, 10]. The predictive factors for bactibilia have been proposed as advanced age, high body temperature, and increased inflammatory markers such as high serum C-reactive protein [9, 11]. However, the association between obesity and bactibilia or bacteremia has not been established.

This study demonstrated that BMI is inversely correlated with bactibilia and bacteremia in patients with acute calculous cholecystitis. According to the study that evaluated the association between BMI and the severity of biliary infections in the United States (US), BMI was not associated with bactibilia. However, BMI was inversely associated with the severity of biliary infections and obesity was postulated as having protective effect on severe infections [12]. From the findings of another study of the Korean population, negative correlation was observed between BMI and the severity of cholecystitis, albeit this was proved only in men [13]. Despite the different study designs and study populations, these studies all indicated that obesity is not associated with severe form or complications of biliary infections. This finding is contrary to the general belief that obese patients are more susceptible to infections. Obesity is also known to be a risk factor for increased morbidity and mortality after infections [14].

Interesting data relevant to this finding is the increased susceptibility or mortality following infection in patients with lower BMI. According to a study of the US population, underweight patients (BMI < 18.5) were associated with increased mortality from non-cancer and non-cardiovascular causes [15]. A Japanese community based study also demonstrated that lower BMI (<18) was associated with mortality of pneumonia, however high BMI (25 >) was postulated as a protective factor [16]. In a study of large Korean cohort, BMI was inversely correlated with mortality from respiratory diseases (tuberculosis, pneumonia, asthma, and chronic obstructive pulmonary disease) [17]. Overall, many ecologic studies indicated that mortality from any cause and BMI shows a J-shaped pattern [17, 18]. However, the exact reason or mechanism of increasing infection in patients with lower BMI is yet unclear and it needs to be elucidated from further studies.

Another explanation is the protective effect of obesity against bacterial infections. Obese patients are known to have high plasma lipoprotein levels. Lipoprotein is known to have capacity of binding and neutralizing lipopolysaccharide (LPS) and lipoteichoic acids which are responsible for the activation of Toll-like receptor 4 mediated host-immune responses [19, 20]. However, general belief is still that patients with obesity are more susceptible to infections [14]. Conflicting results that fit the general belief like impaired lymphocyte proliferation to polyclonal stimulation or pro-inflammatory state of mononuclear cells in obese patients still exist [21, 22]. The association between obesity and infection may not be generalized. This might be site-specific. Biliary infections are characterized by ascending form from the duodenum or hematogenous spread from the portal vein, which is called cholangiovenous reflux [12]. According to the studies that evaluated the pathophysiology of biliary bacterial infections, LPS induced inflammatory cytokine activation was the important factor of illness severity [23, 24]. It is unclear whether obesity has a positive role in the prevention of biliary infections only. Site-specific studies are needed to confirm this result.

In terms of the hormonal changes of obese patients, adiponectin which is one of the important adipokines is known to reduce proinflammatory cytokines and increase anti-inflammatory cytokines [25]. However, another important adipokine, leptin is known to have the capacity to up-regulate vascular adhesion molecules, and to subsequently induce inflammatory cascade [25]. The combination of these adipokines is associated with metabolic syndrome and the development of cancers, however the association between adipokines and infections (bactibilia or bacteremia) is not well established. Considering the visceral fat that produces various adipokines, studies on the role of visceral fat, including adipokines will give clues about the inverse association between obesity and biliary infections.

Another finding from this study was the bacteriologic profiles of bactibilia and bacteremia. The microbial culture rates of biliary bacteria and bacteremia were not different from those in previous studies (50.4%, 21.6%) [11, 12]. E. coli and Klebsiella spp. were the most prevalent biliary organisms in accordance with the Japanese study [11]. However, the proportion of ESBL and VRE was relatively high which means increased resistance and unresponsiveness to previously used empirical antibiotics. Therefore, interpretation of these results demands caution. Since, many cases were excluded from this study due to the lack of laboratory results of bile and blood cultures, only relatively serious cases could be finally enrolled.

This study has several limitations. It was a retrospective study from single teaching hospital and a small number of patients was enrolled for the statistical analysis. Another limitation is the lacking information about type and number of GB stone and Lipoprotein level was not measured consistently from enrolled patients. However, contrary to the previous studies that assessed the association between obesity and the severity of biliary infections, this study evaluated the direct association between obesity and bactibilia and bacteremia in patients with cholecystitis.

In conclusion, BMI is inversely correlated with bacteremia or bactibilia, which means obese or overweight patients are less likely to be associated with bacteremia or bactibilia in patients with acute calculous cholecystitis.