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.
466 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 4, July 2011
However, when a contraindication for the use of EN
is present or when patients cannot tolerate EN, PN is
essential for maintaining nutrition status and metabo-
lism. Although glutamine (GLN) supplementation of PN,
neuropeptides, and interleukin 7 (IL-7) intravenous (IV)
injection have been regarded as possible surrogates for
EN in animal experimental models,11-16 these therapies
are far from clinical application, with the exception of
GLN supplementation of PN.
Prebiotics and dietary carbohydrates escaping diges-
tion/absorption in the small intestine undergo fermenta-
tion in the colon and give rise to short-chain fatty acids
(SCFAs).17 Numerous recently reviewed physiologic and
clinical studies have shown that SFCAs in general and
butyric acid in particular can be a significant source of
calories and that their trophic effects on both the small
and large intestines may be useful for the prevention
and treatment of several acute and chronic condi-
tions.18-20 Most notably, some probiotics and prebiotics
can stabilize the intestinal barrier and prevent bacterial
translocation and infections.21 In the intestinal lumen,
probiotics ferment prebiotics, which leads to the pro-
duction of butyric acid and other SCFAs. Moreover, IV
administration of SCFAs ameliorated mucosal atrophy,22
and butyric acid–supplemented PN (Bu-PN) both
increased intestinal mucosal protein synthesis23 and
stimulated the growth of jejunal and ileal cells in a mas-
sive intestinal resection model.24
However, the effects of Bu-PN on the mass and
function of GALT, a center of intestinal and systemic
mucosal immunity, remain unclear. Therefore, in the
present study, we examined whether administering
Bu-PN leads to restoration of PN-induced reductions in
GALT mass and secretory immunoglobulin A (IgA) lev-
els, a primary immunologic component of the extrinsic
protective mechanism of the mucosal surface, in the
small intestine and the respiratory tract. In experiment
1, we evaluated lymphocyte numbers in Peyer’s patches
(PPs), an important GALT site of mucosal immunity
induction, and small intestinal IgA levels. We also deter-
mined the phenotypes of lymphocytes isolated from PPs,
because phenotypic changes in PP lymphocytes would
lead to alterations in intestinal immunity. In experiment
2, we examined respiratory IgA levels. Finally, in experi-
ment 3, we assessed small intestinal morphology.
Materials and Methods
Specific pathogen-free, 6-week-old, male Institute of
Cancer Research mice (n = 103; Nippon SLC, Hamamatsu,
Japan) were housed under controlled temperature and
humidity conditions with a 12-hour light/dark cycle. Mice
were fed standard chow (CE7; Clea Japan, Tokyo, Japan)
with free access to water for 1 week before protocol entry.
All studies were approved by the Animal Experiment
Committee of the National Defense Medical College.
All mice were given general anesthesia (ketamine hydro-
chloride 100 mg/kg and xylazine 10 mg/kg mixture) and
underwent implantation of silicone rubber catheters (0.3-
mm inner diameter, and 0.5-mm outer diameter; DETAKTA,
Hamburg, Germany) into the right jugular vein. A silicone
rubber catheter was inserted into the vena cava via the
right internal jugular. The proximal end of each catheter
was tunneled subcutaneously over the spine and exited the
tail at its midpoint. The mice were placed in metal metab-
olism cages and partially immobilized by tail restraint to
protect the catheter during infusion. This technique is an
acceptable method of nutrition support that does not
induce physical or biochemical stress.25 Catheterized mice
were immediately connected to an infusion pump (TE-
331; Terumo, Tokyo, Japan).
Experimental Design and Nutrition Support
The experimental protocol is shown in Figure 1. After a
2-day recovery from surgical stress, all mice were random-
ized to either the control, S-PN, or Bu-PN group. The
control group received chow and water ad libitum with
continuous infusion of a 0.9% saline solution, 4.8 mL/day
via jugular vein catheter. The S-PN group was given
standard PN solution via jugular vein catheter, while the
Bu-PN group was given Bu-PN solution. The S-PN and
Bu-PN formulas are essentially identical except for
the amount of SCFAs. The S-PN solution contained
94 mmol/L acetic acid, while the Bu-PN solution con-
tained 47 mmol/L acetic acid and 47 mmol/L butyric acid
(Table 1). The S-PN and Bu-PN solutions were supple-
mented with micronutrients (Elemenmic; Ajinomoto,
Tokyo, Japan) and multivitamins (MVI-SS; SS-Seiyaku Co,
Tokyo, Japan). The S-PN solution provided 1,438 kcal/L
with a ratio of nonprotein calories to nitrogen ratio of
210:1, while the Bu-PN solution provided 1,442 kcal/L
with the same nonprotein calories:nitrogen ratio. The
S-PN and Bu-PN groups were advanced from 4.8 mL/day
PN solution to a target rate of 9.6 mL/day (14.0 kcal/day)
by the third day of feeding (day 1, 0.2 mL/h; day 2, 0.3
mL/h; days 3–5, 0.4 mL/h), because a graded infusion
period was demonstrated to be necessary to allow the mice
to adapt to the glucose and fluid loads.26 The maximal total
daily caloric intakes in the S-PN and Bu-PN groups were
determined based on the daily chow intake of free-fed
Effects of Butyric Acid on GALT and Mucosal IgA Levels / Murakoshi et al 467
After 5 days of feeding, the first set of mice (control
group, n = 12; S-PN group, n = 11; Bu-PN group, n = 10)
were given general anesthesia. The mice were then
weighed and exsanguinated by cardiac puncture. The
entire small intestine was harvested for PP lymphocyte
isolation and measurement of small intestinal IgA levels.
After receiving the respective diets for 5 days, as in exper-
iment 1, the second set of mice (control group, n = 12;
S-PN group, n = 12; Bu-PN group, n = 13) were used for
measurement of respiratory tract IgA levels.
A third set of mice (control group, n = 10; S-PN group,
n = 12; Bu-PN group, n = 11) received the same diets for
5 days as the mice in experiment 1. These mice were used
for measurement of villous height and crypt depth in the
jejunum and ileum.
PP Cell Isolation
PPs were excised from the serosal side of the intestine
and teased apart. The fragments were treated with
collagenase (Sigma, St Louis, MO; 40 U/mL) in
RPMI-1640 culture medium for 60 minutes at 37°C
with constant shaking. After collagenase digestion,
the cell suspensions were passed through nylon filters.
Lymphocytes were isolated from PPs using a modifica-
tion of the method described by Li et al.27
To determine the phenotypes of lymphocytes isolated
from PPs, 1 × 105 cells were suspended in 50 µL Hank’s
balanced salt solution (HBSS) containing fluorescein
isothiocyanate (FITC) anti-mouse γδTCR (clone
GL3; Caltag, Burlingame, CA) and phycoerythrin (PE)-
conjugated anti-mouse αβTCR (clone H57–597;
Pharmingen, San Diego, CA) to identify γδTCR+ T cells
and αβTCR+ T cells, respectively, or PE-anti-CD4
(clone CT-CD4; Caltag) and FITC-anti-CD8α (clone
CT-CD8α; Caltag) to identify the 2 T-cell subsets, or
FITC-anti-CD45R (B220) (clone RA3–6B2; Caltag) to
identify B cells. All antibodies were diluted to 1 mg/mL
in HBSS containing 1% fetal bovine serum (FBS).
Incubations were carried out for 30 minutes at 4°C.
After staining, the cells were washed twice in HBSS
with 1% FBS and fixed in 1% paraformaldehyde.
Flowcytometric analysis was performed on an Epics XL
(Coulter, Hileah, IL).
Small intestinal washings for IgA level measurement
were obtained by flushing the small intestine with a total
of 20 mL chilled HBSS. Nasal and bronchoalveolar
washings for measurement of respiratory tract IgA levels
were obtained by lavage with 1 mL phosphate-buffered
saline solution under anesthesia. The washings were
Figure 1. Experimental protocol. Bu-PN, butyric acid–supplemented parenteral nutrition; IV, intravenous; S-PN, standard
468 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 4, July 2011
stored in a –80°C freezer until IgA analysis. IgA was
measured in small intestinal and respiratory tract wash-
ings by sandwich enzyme-linked immunosorbent assay
using a polyclonal goat anti-mouse IgA (Sigma) to coat
the plate, a purified mouse IgA (Zymed Laboratories,
San Francisco, CA) as the standard, and a horseradish
peroxidase–conjugated goat anti-mouse IgA (Sigma).
Jejunal samples for assessing morphology were taken
from a distal portion 2 to 3 cm from the pylorus. Ileal
samples were taken from a proximal portion 2 to 3 cm
from the ileocecal valve. These specimens were fixed in
10% buffered formalin and embedded in paraffin
blocks. Sections were cut into 4-µm sections and
stained with hematoxylin and eosin for histomorphol-
ogy. Small intestinal morphology evaluations were
made based on a mean height of 5 villi and a mean
depth of 5 crypts per section. All measurements were
made under light microscopy at ×40 or ×100 magnifi-
cation in a blinded manner.
Results are presented as mean ± standard deviation.
Statistical significance was determined using analysis of
variance followed by the post hoc test of Fisher protected
least significant difference. Differences were considered
statistically significant at P < .05.
Body Weight Change
At the beginning of experiment 1, there were no signifi-
cant differences in body weight among the 3 groups.
Table 2. Pre–experimental Body Weight and Weight Change After Feeding
Groupn Body weight (g)Weight change (g)
35.7 ± 2.8
34.7 ± 2.5
35.7 ± 3.5
–0.3 ± 1.1
–4.1 ± 2.5a
–3.3 ± 1.3a
Values are mean ± standard deviation. aP < .05 vs control group. Bu-PN, butyric acid–supplemented parenteral nutrition; S-PN,
standard parenteral nutrition.
Table 3. PP Lymphocyte Numbers and its Phenotype Percentages
Phenotype of PP lymphocytes (%)
γδTCR+CD4+ CD8+ B220+
Values are mean ± standard deviation. aP < .05 vs S-PN group. bP < .05 vs Bu-PN group. Bu-PN, butyric acid–supplemented
parenteral nutrition; PP, Peyer’s patch; S-PN; standard parenteral nutrition.
30.4 ± 9.0a,b
13.2 ± 4.8
20.7 ± 4.3a
25.1 ± 4.4
29.0 ± 4.9
27.8 ± 7.8
1.0 ± 0.5
1.2 ± 0.7
1.3 ± 0.8
22.2 ± 6.1
26.3 ± 6.8
23.8 ± 6.7
3.5 ± 1.3
4.8 ± 1.7
4.0 ± 1.0
52.5 ± 9.5
54.0 ± 5.8
50.0 ± 8.7
Table 1. Compositions of Parenteral Nutrition (PN) Solution and Chow (per 1,000 kcal)
Chow GroupS-PN GroupBu-PN Group
Amino acids (g)
Non protein calories/N ratio (kcal/g)
Acetic acid (mmol)
Butyric acid (mmol)
64 (94 mmol/L)
32 (47 mmol/L)
32 (47 mmol/L)
Bu-PN, butyric acid–supplemented PN; S-PN, standard PN.
Effects of Butyric Acid on GALT and Mucosal IgA Levels / Murakoshi et al 469
After feeding, weight loss was significantly greater in the
S-PN and Bu-PN groups than in the control group, but
there was no significant difference between the S-PN
and Bu-PN groups (Table 2).
Number of Lymphocytes Isolated From PPs
The total number of lymphocytes isolated from PPs
was significantly lower in the S-PN group than in
the control group. Bu-PN moderately but significan-
tly increased the lymphocytes compared with S-PN
PP Lymphocyte Phenotypes
There were no significant differences in the percentages
of αβTCR+, γδTCR+, CD4+, CD8+ or B220+ cells among
the 3 groups (Table 3).
IgA Levels of Intestinal Washings
IgA levels were significantly lower in the S-PN group
than in the control group. However, Bu-PN signifi-
cantly increased IgA levels as compared with S-PN
IgA Levels of Respiratory Tract Washings
IgA levels of nasal and bronchoalveolar washings were
significantly lower in the S-PN group than in the control
group. Bu-PN moderately restored IgA levels of nasal and
bronchoalveolar washings as compared with S-PN. The
difference did not, however, reach statistical significance
for the nasal IgA level (Figure 3).
Villous Height and Crypt Depth
in the Small Intestine
In the jejunum and ileum, villous height and crypt depth
were both significantly lower in the S-PN than in the
control group. Bu-PN moderately but significantly
restored both of these parameters as compared with S-PN
(Table 4; Figure 4).
GALT, a form of lymphoid tissue, has been considered a
center of mucosal immunity because of its mass and func-
tion.28 GALT is divided into inductive sites, PPs, and effec-
tor sites, the intraepithelial (IE) space and lamina propria
(LP). Because luminal antigens are sampled, processed,
and presented to unprimed T and B cells in PPs and primed
lymphocytes migrate to intestinal effector and extraintesti-
nal mucosal sites, including the respiratory tract,28 restora-
tion of PP-cell numbers appears to be essential for
improvement in intestinal and systemic mucosal immunity.
Thus, we focused on PP-cell numbers and found that
Bu-PN moderately restores PP-lymphocyte numbers
reduced by PN without markedly changing phenotypes. In
association with this recovery of PP-lymphocyte numbers,
intestinal and respiratory tract IgA levels were increased in
the Bu-PN group as compared with the S-PN group.
The mechanisms underlying the restoration of PP-cell
numbers in the Bu-PN group were not clarified in the
present study. In a porcine feeding model, researchers
found that long-term intake of resistant starch increased the
butyric acid concentration in colon digests with a reduction
in PP-cell apoptosis, as compared with digestible starch.29
IV butyric acid may also have restored PP-cell numbers by
reducing PP-cell apoptosis. These reductions might have
occurred for all PP-lymphocyte phenotypes examined,
resulting in no marked change in phenotypic percentages.
Although we did not evaluate numbers of GALT
effector-site lymphocyte in the present study, increased
intestinal IgA levels suggest that Bu-PN may also have
restored IE and LP lymphocyte numbers because IgA-
producing cells in the LP are the main source of intestinal
secretory IgA.30 Moreover, butyric acid upregulates the
adhesion molecules ICAM-1 (intercellular adhesion mol-
ecule 1) and E-selectin are on vascular endothelial cells.31
The observation that B-cell adhesion to endothelial cells is
mediated by the integrin LFA-1 (lymphocyte function–
associated antigen 1) and its ligand ICAM-132 in particular
may support the possibility that butyric acid increases the
migration of primed B lymphocytes to effector sites.
Figure 2. Immunoglobulin A levels in small intestinal
washings. Values are mean ± standard deviation. aP < .05 vs
S-PN group. bP < .05 vs Bu-PN group. Bu-PN, butyric acid–
supplemented parenteral nutrition; S-PN, standard parenteral
470 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 4, July 2011
Intestinal IgA production is affected not only by the
size of GALT effector sites but also by IgA-mediating
cytokines. It was documented that parenteral feeding
reduces levels of IL-4 and IL-10, both Th2 IgA-stimulating
cytokines, but does not change the level of interferon-
gamma (IFN-γ), a Th1 IgA-inhibiting cytokine, in the
small intestine.33 Another group reported a PN-related
intestinal IFN-γ increase in C57BL/6J mice.34 Taken
together, these reports suggest an imbalance in the intes-
tinal cytokine milieu to be a very important mechanism
for PN-induced reduction of intestinal IgA production.
Of interest, butyric acid has been identified as a histone
deacetylase (HDAC) inhibitor17,35 and in vitro inhibition
of HDAC in T lymphocytes reportedly suppressed IFN-γ
production.36 Considering these reports, the increased
intestinal IgA levels in our study may have been due to a
decrease in the intestinal IFN-γ level resulting from
butyric acid functioning as an HDAC inhibitor.
In the present study, respiratory IgA levels were
also moderately restored in the Bu-PN group. Given the
Figure 4. Jejunal and ileal histologies in control, S-PN, and Bu-PN groups. Original magnification: ×40. Bu-PN, butyric acid–
supplemented parenteral nutrition; S-PN, standard parenteral nutrition.
Figure 3. A. Immunoglobulin A (IgA) levels in bronchoalveolar washings. B. IgA levels in nasal washings. Values are mean ± standard
deviation. aP < .05 vs S-PN group. bP < .05 vs Bu-PN group. Bu-PN, butyric acid–supplemented parenteral nutrition; S-PN, standard
Effects of Butyric Acid on GALT and Mucosal IgA Levels / Murakoshi et al 471
presence of a common form of mucosal immunity, resto-
ration of PP cell numbers may have led to the increased
respiratory IgA levels in animals fed Bu-PN. Clinically,
once severe infectious complications occur in the respira-
tory tract, hospitalization is prolonged and the mortality
rate increases markedly.2-4,37 Therefore, it may be reason-
able to assume that Bu-PN contributes to the prevention
of such complications.
Our study also demonstrated that Bu-PN restored
PN-induced morphological atrophy in the jejunum and
ileum. PN is known to induce significant changes in
mucosal structure.38,39 It was reported that small intestinal
epithelial cell apoptosis is significantly elevated with PN.40
Butyric acid was identified as the SCFA responsible for
increasing proliferation and decreasing apoptosis of epithe-
lial cells in a neonatal piglet model with massive small intes-
tinal resection.24 Likewise, IV administration of butyric acid
may have been responsible for the small intestinal morphol-
ogy restoration during PN in this study.
Various factors are possibly related to PN-induced
GALT changes. Lack of a direct nutrition supply from the
intestinal lumen to the mucosa, absence of a GLN supply,
changes in intestinal commensal bacteria, decreased neu-
ropeptide release, and reduced IL-7 production by intes-
tinal epithelial cells have all been suggested as important
factors influencing GALT.11-16,41 Therefore, it is not sur-
prising that butyric acid supplementation does not com-
pletely reverse the GALT changes developing in the
absence of enteral feeding. However, it is surprising that
just a small alteration in the SCFA composition of PN
solution significantly improved PP-cell numbers and
mucosal IgA levels. Because survival during PN feeding
was similar in the Bu-PN and S-PN groups and no toxic
effects were observed in the Bu-PN animals, we believe
that this new Bu-PN formula is a potentially novel option
for the maintenance of mucosal immunity in patients
who cannot receive or tolerate EN. Before clinical use,
however, further studies are necessary.
We determined the butyric acid dose in the PN solu-
tion referring to a previous report demonstrating supple-
mentation of PN formula with 60 mmol/L butyric acid to
reverse PN-induced atrophy and stimulate both the struc-
tural and the functional aspects of intestinal adaptation in
a small intestinal massive resection model using neonatal
piglets.24 However, the optimal dose for recovery of mucosal
immunity remains uncertain. A higher dose of butyric acid
in PN might be more beneficial or, in contrast, more detri-
mental. Indeed, excess butyric acid is reportedly toxic to
mucosal cells.42,43 Butyric acid at a low concentration pro-
moted intestinal barrier function, while a high concentra-
tion caused interruption of the intestinal barrier.44
In the present study, we focused on butyric acid sup-
plementation. Other SCFAs have also been demonstrated
to have beneficial effects. For example, propionic acid has
a favorable impact on cholesterol levels and colonocyte
proliferation and differentiation.17,18 The addition of other
SCFAs to PN might restore PN-induced impairment of
intestinal immunity to some degree.
In conclusion, adding butyric acid to PN moderately
reverses PN-induced GALT atrophy and improves secre-
tory IgA levels in the intestinal and extraintestinal mucosa.
Moreover, it moderately recovers the mucosal atrophy
associated with PN. Bu-PN is potentially a new option for
ameliorating impairment of intestinal immunity during
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Table 4. Villous Height and Crypt Depth in the Small Intestine (µm)
Group Villous heightCrypt depth Villous heightCrypt depth
488 ± 74a,b
310 ± 66
404 ± 42a
115 ± 19a
80 ± 10
102 ± 30a
255 ± 58a,b
160 ± 27
206 ± 38a
97 ± 17a,b
65 ± 12
78 ± 12a
Values are mean ± standard deviation. aP < .05 vs S-PN group. bP < .05 vs Bu-PN group. Bu-PN, butyric acid–supplemented
parenteral nutrition; S-PN, standard parenteral nutrition.
472 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 4, July 2011
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