T Lymphocyte Numbers in Human Gut Associated Lymphoid Tissue Are Reduced Without Enteral Nutrition 
From the * Department of Surgery I and Correspondence: Kazuhiko Fukatsu, MD, Division of Basic Traumatology, National Defense Medical College Research Institute, 3–2 Namiki, Tokorozawa, Saitama, Japan. Electronic mail may be sent to fukatsu{at}res.ndmc.ac.jp.
Background: Clinically, in the absence of enteral nutrition, the morbidity of infectious complication is high. Although experiments using mice have shown alterations in gut-associated lymphoid tissue (GALT) to be an important mechanism underlying impaired host defense, there are no clinical studies on the effects of nutritional routes on GALT. Methods: A total of 27 colon cancer cases who underwent right colectomy or hemicolectomy were reviewed. Six patients did not receive enteral nutrition for 4 to 28 days before surgery because of bowel obstruction (parenteral nutrition [PN] group). Twenty-one patients were enterally fed before surgery (enteral nutrition [EN] group). The terminal ileum from resected specimens was examined microscopically. T-cell numbers in intraepithelial spaces (IE) and the lamina propria (LP) were determined immunohistochemically in blinded fashion. Results: There were no significant differences in baseline characteristics between the 2 groups. T-cell number in the LP was significantly lower in the PN group than in the EN group, with no difference in IE cell numbers. Conclusions: Lack of enteral delivery of nutrients reduces GALT cell number in patients with colon cancer, as is the case in mice. In the absence of enteral nutrition, infectious complications including pneumonia and intraabdominal abscess are increased in critically ill or severely injured patients.1,2 Mechanisms underlying this increased susceptibility have been extensively explored. Changes in mucosal immunity, associated with nutritional route, are considered to be a plausible mechanism.3 The gut-associated lymphoid tissue (GALT) provides immunologic protection against intraluminal bacteria and toxins.4 The route and type of nutrition influence GALT cell mass and function. In a murine feeding model, IV and intragastric parenteral nutrition decreased GALT cell numbers and intestinal IgA levels compared with complex enteral and chow diets.3,5 However, there are no clinical studies on the effects of nutritional routes on GALT, because of the difficulty in isolating lymphocytes from individual GALT compartments. In this study, we retrospectively examined terminal ileum specimens from patients who underwent right colectomy or right hemicolectomy. We report, for the first time, the influence of lack of enteral nutrition on T lymphocyte number in human GALT.
From 1997 to 1999, in our department of surgery at the National Defense Medical College, we identified 6 patients who underwent right colectomy or right hemicolectomy because of colon cancer without enteral or oral feeding for 4–28 days (4, 7, 10, 10, 14, and 28 days) before surgery. These patients had severe colonic stricture because of their tumors but did not have complete obstruction or dilatation of the intestine and thus did not need treatment with a short or long decompression tube. These patients were fed only parenterally before the operation (PN group). We randomly chose 21 patients who were fed normal food before surgery and underwent the same type of operation during this period (EN group). The terminal ileum from resected specimens had been fixed in buffered formalin and embedded in paraffin. Tissue sections (6 µm) were mounted on a glass slide and deparaffinized. T-cells were stained immunohistochemically with a mouse monoclonal antihuman T-cell antibody (CD45RO, T-cell, UCHL1; Dako Cytomation, Kyoto, Japan) or a mouse negative control antibody. T-cells were counted in the intraepithelial (IE) space and lamina propria (LP), 3 fields each, under 400x magnification in blinded fashion. Statistical analysis was performed using the Student's t test. The level of statistical significance was p < .05. Data are expressed as means ± SEM.
Table I presents patient characteristics. The PN group ages ranged from 50–81 years, whereas EN patients were 45–86 years old. There were no significant differences in age, sex, BMI, serum total protein, serum albumin, or stage of cancer between the 2 groups. Patients were classified according to the Japanese colon cancer staging system. With regard to postoperative complications, infectious complications occurred in 1 PN group patient but none of the EN group patients. Noninfectious complications occurred in 1 PN and 6 EN group patients. Thus, there were no significant differences in postoperative complication rate between the 2 groups.
Immunostaining was used to localize and count T-cells in GALT. No nonspecific staining was seen with control murine IgG antibody (Fig. 1). Typical results are presented in Figure 2. Positive cells are sparse in the IE space, whereas being relatively numerous in the LP. Under 400x magnification, IE and LP T-cells were clearly visualized (Fig. 3). There was no significant difference in IE T-cell number between the 2 groups. However, the number of LPT-cells was significantly higher in the EN group than in the PN group (Fig. 4).
GALT is a major component of mucosal immunity. Naïve T- and B-cells are sensitized within Peyers patches (PPs), inductive sites for mucosal immunity.4 Sensitized lymphocytes home to various mucosal areas, including the intestinal LP and IE space, respiratory tract, and genitourinary tract, producing IgA or maintaining epithelial integrity. Thus, the LP and IE space are effector sites for the mucosal system. Kudsk et al,3 using murine feeding models, have demonstrated that lack of enteral nutrition reduces GALT mass and function by isolating lymphocytes from PPs, the LP, and the IE space.5,6 Unfortunately, PPs are much less prominent in humans than in mice.4 It is difficult to isolate and quantify lymphocytes from individual components of human GALT. Therefore, no clinical evidence that such changes would occur in human GALT has previously been obtained. Here, for the first time, we have demonstrated the association between nutritional route and GALT cell number. Our data confirm that changes similar to those in rodents occur even in human GALT, when the gut is not fed enterally. Lymphocyte number in the LP was significantly lower in the PN than in the EN group. With regard to IE lymphocytes, there was no significant difference between the 2 groups. However, it may be premature to conclude that lack of enteral nutrient delivery does not influence IE cell number, because we were only able to examine terminal ileum specimens, whereas animal experiments evaluated cells from the entire small intestine. Malnutrition has been demonstrated to impair host immunity.7,8 To exclude the possibility that nutritional status before surgery affected GALT cell number, we compared certain nutritional parameters. There were no significant differences in BMI, total protein or albumin levels between the PN and EN groups, although patients in the 2 groups had relatively low BMIs. We need to be aware that the tumor or the obstruction might have affected the GALT cell number in this study. Because there are several reports demonstrating some colon cancer to originate in areas of GALT aggregates,9,10 tumor itself might have influenced the GALT cell number. Moreover, although the PN patients did not have complete obstruction of the intestine, even slight obstruction might have affected the cell number in this study. This is a preliminary retrospective study. To fully elucidate this relationship, prospective studies with large numbers of patients must be conducted. Nonetheless, we believe that the present study provides a valuable insight into the significance of nutrition therapy.
Colon cancer patients receiving preoperative enteral or parenteral nutrition were studied. Parenteral feeding reduced T-cell numbers in the lamina propria of terminal ileum specimens, as compared with enteral feeding. This paper was presented at Nutrition Week 2004, February 9–12, 2004, Las Vegas, Nevada. Received for publication April 23, 2004. Accepted for publication October 11, 2004.
Journal of Parenteral and Enteral Nutrition, Vol. 29, No. 1,
56-58 (2005) This article has been cited by other articles:
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MATERIALS AND METHODS
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