Journal of Parenteral and Enteral
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2011 35: 465 originally published online 5 April 2011JPEN J Parenter Enteral Nutr
Satoshi Murakoshi, Kazuhiko Fukatsu, Jiro Omata, Tomoyuki Moriya, Midori Noguchi, Daizoh Saitoh and Isamu Koyama
Effects of Adding Butyric Acid to PN on Gut-Associated Lymphoid Tissue and Mucosal Immunoglobulin
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Journal of Parenteral and Enteral Nutrition
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Journal of Parenteral and
Volume 35 Number 4
July 2011 465-472
© 2011 American Society for
Parenteral and Enteral Nutrition
Clinical Relevancy Statement
Parenteral nutrition (PN) is indispensable for prevent-
ing malnutrition in patients who cannot tolerate enteral
nutrition. However, absence of enteral delivery of
nutrients results in impaired gut function. The present
From the 1Division of Traumatology, National Defense Medical
College Research Institute, Tokorozawa, Japan; 2Gastrointestinal
Center, Saitama Medical University International Medical
Center, Hidaka, Japan; 3Surgical Center, The University of
Tokyo, Tokyo, Japan; and 4Department of Surgery, National
Defense Medical College, Tokorozawa, Japan.
This manuscript was presented at the 46th Annual Meeting of the
Japanese Society for Surgical Metabolism and Nutrition in 2009.
Received for publication December 15, 2009; accepted for pub-
lication September 1, 2010.
Address correspondence to: Kazuhiko Fukatsu, MD, PhD,
Surgical Center, The University of Tokyo, Tokyo, Japan 7-3-1
Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan; e-mail; fukatsu-
study proposes a new formula of PN which can pre-
serve gut morphology and immunity to some degree.
Clinical use of butyric acid-supplemented PN may be
expected to improve patients’ outcome.
Enteral nutrition (EN) has long been the standard for
the nutrition management of critically ill and severely
injured patients.1 The use of EN is associated with a sig-
nificant reduction in the morbidity of infectious compli-
cations in these patient populations, as compared with
parenteral nutrition (PN).2-4 Advantages of EN over PN
have been clarified in terms of host responses to various
insults.5-8 It has been demonstrated that EN preserves
systemic mucosal immunity through the maintenance of
gut-associated lymphoid tissue (GALT) mass and func-
tion, thereby preventing respiratory tract infections and
Background: Parenteral nutrition (PN) causes intestinal mucosal
atrophy, gut-associated lymphoid tissue (GALT) atrophy and
dysfunction, leading to impaired mucosal immunity and
increased susceptibility to infectious complications. Therefore,
new PN formulations are needed to maintain mucosal immu-
nity. Short-chain fatty acids have been demonstrated to exert
beneficial effects on the intestinal mucosa. We examined the
effects of adding butyric acid to PN on GALT lymphocyte num-
bers, phenotypes, mucosal immunoglobulin A (IgA) levels, and
intestinal morphology in mice. Methods: Male Institute of
Cancer Research mice (n = 103) were randomized to receive
either standard PN (S-PN), butyric acid–supplemented PN
(Bu-PN), or ad libitum chow (control) groups. The mice were
fed these respective diets for 5 days. In experiment 1, cells were
isolated from Peyer’s patches (PPs) to determine lymphocyte
numbers and phenotypes (αβTCR+, γδTCR+, CD4+, CD8+,
B220+ cells). IgA levels in small intestinal washings were also
measured. In experiment 2, IgA levels in respiratory tract (bron-
choalveolar and nasal) washings were measured. In experiment
3, small intestinal morphology was evaluated. Results:
Lymphocyte yields from PPs and small intestinal, bronchoalveo-
lar, and nasal washing IgA levels were all significantly lower in
the S-PN group than in the control group. Bu-PN moderately,
but significantly, restored PP lymphocyte numbers, as well as
intestinal and bronchoalveolar IgA levels, as compared with
S-PN. Villous height and crypt depth in the small intestine were
significantly decreased in the S-PN group vs the control group,
however Bu-PN restored intestinal morphology. Conclusions: A
new PN formula containing butyric acid is feasible and would
ameliorate PN-induced impairment of mucosal immunity.
(JPEN J Parenter Enteral Nutr. 2011;35:465-472)
Keywords: butyric acid; mucosal immunity; Peyer’s patches;
Effects of Adding Butyric Acid to PN
on Gut-Associated Lymphoid Tissue
and Mucosal Immunoglobulin A Levels
Satoshi Murakoshi, MD1,2; Kazuhiko Fukatsu, MD, PhD3;
Jiro Omata, MD4; Tomoyuki Moriya, MD, PhD4;
Midori Noguchi, BS1; Daizoh Saitoh, MD, PhD1; and
Isamu Koyama, MD, PhD2
Financial disclosure: None declared.
472 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 4, July 2011
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