Download Combination Therapy with Bifidobacterium breve, Lactobacillus

Digestive Diseases and Sciences, Vol. 46, No. 9 (September 2001), pp. 2010 –2016 (© 2001)
CASE REPORT
Combination Therapy with Bifidobacterium
breve, Lactobacillus casei, and
Galactooligosaccharides Dramatically
Improved the Intestinal Function in a Girl
with Short Bowel Syndrome
A Novel Synbiotics Therapy for Intestinal Failure
YUTAKA KANAMORI, MD,* KOHEI HASHIZUME, MD,* MASAHIKO SUGIYAMA, MD,*
MASAMI MOROTOMI, PhD,† and NORIKATSU YUKI†
KEY WORDS: synbiotics; short bowel syndrome; bacterial overgrowth syndrome.
It has been well known since ancient times that fermented milk produces beneficial effects on the consumer’s health. In the last few decades, these beneficial
effects have been demonstrated to be due to the metabolic action of some bacterial species, including lactobaccilli, bifidobacteria, and streptococci (1–3). Lilly et al.
first introduced the term probiotics for such bacteria in
1965 (4). Probiotics are widely used as a live microbial
feed supplement that beneficially affects the host animals by improving their intestinal microbial balance (5).
Additionally the term prebiotics has been adopted to
refer to a nondigestive food ingredient that selectively
targets the growth and/or activity of one or a limited
number of bacteria in the colon and, thus, has the
potential to improve host health. Several types of ingredients, such as fructooligosaccharides, galactooligosaccharides, and inulin, are used as prebiotics (2, 6). Furthermore, the combined use of probiotics and prebiotics
is called synbiotics therapy, but few reports concerning
synbiotics have been published (7, 8).
Short bowel syndrome refers to seriously adverse
symptoms that are seen in patients who have been
Manuscript May 30, 2000; accepted November 1, 2000.
From the *Department of Pediatric Surgery, Faculty of Medicine, University of Tokyo, and †Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Address for reprint requests: Yutaka Kanamori, Department of
Pediatric Surgery, Faculty of Medicine, University of Tokyo, 7-3-1
Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
2010
subjected to a massive bowel resection. These patients are usually malnourished and have a dilated
intestine that results in intestinal bacterial overgrowth
syndrome (9, 10). Regulation of intestinal bacterial
overgrowth, especially pathogenic bacterial overgrowth, is very important in patients with short bowel
syndrome to attain any improvement in intestinal
function. For this purpose, various antibiotics have
been used to eliminate the intestinal bacteria selectively. An alternative strategy for regulating intestinal
bacteria is to apply probiotics and/or prebiotics.
In this report, we report the use of synbiotics therapy in the treatment of a 4-year-old girl suffering from
short bowel syndrome. For the synbiotics therapy, we
used Bifidobacterium breve, Lactobacillus casei, and
galactooligosaccharides. This novel combination therapy was expected to act synergistically for the improvement of the subject’s health. We found that the
patient’s intestinal absorptive function and motility
were dramatically improved by this newly designed
synbiotics therapy, and she progressed satisfactorily
after 2 years of the therapy. Following the case report,
we discuss the beneficial effects of the new synbiotics
therapy for intestinal failure.
CASE REPORT
The patient was diagnosed with gastroschisis as a fetus
and delivered by cesarean section in 1994. After delivery,
Digestive Diseases and Sciences, Vol. 46, No. 9 (September 2001)
0163-2116/01/0900-2010$19.50/0 © 2001 Plenum Publishing Corporation
A NOVEL SYNBIOTICS THERAPY
Fig 1. The clinical course of the patient as defined by changes in body weight and serum
choline esterase levels before and after the start of the synbiotics therapy. Body weight gain
was dramatically accelerated after starting the synbiotics therapy. The serum choline
esterase value also increased after the commencement of synbiotics therapy. On the other
hand, the episodes of repetitive high fever attacks (E) and severe metabolic acidosis (‚)
ceased abruptly soon after the introduction of synbiotics treatment.
she underwent surgery to repair the abdominal wall defect
on the same day. Multiple intestinal perforations and severe
adhesions between the intestinal tracts indicated the need
for a massive intestinal resection, resulting in a residual
small intestine of 25 cm. The patient survived the procedure, recovered from the acute phase of short bowel syndrome, and progressed for 2 years. She received an elemental formula diet and intravenous hyperalimentation
simultaneously, but her height and body weight were not
within normal values for her age, as judged by the standard
growth curve of Japanese girls. In addition, she suffered
repetitive high fever attacks and severe metabolic acidosis
at least once a month (Figure 1). These symptoms were
considered to be caused by enterocolitis resulting from a
bacterial overgrowth of the intestine and/or a central venous catheter sepsis. Therefore, we decided to discontinue
the use of a central venous catheter, and, to control the
bacterial overgrowth, we began the administration of synbiotics orally.
The synbiotics used consist of the three agents: Bifidobacterium breve Yakult (BBG-1) (11), Lactobacillus casei Shirota (BIOLACTIS Powder) (12), and galactooligosaccharides (Oligomate HR). These bacteria and oligosaccharides
were developed and supplied by the Yakult Central Institute, Japan. Each 1.0-g pack of Bifidobacterium breve and
Lactobacillus casei included more than 1 ⫻ 109 bacteria,
respectively, and we administered these agents at 3.0 g per
day. Galactooligosaccharides were also administered at 3.0
g per day. We monitored the growth of the patient through
body weight and blood tests. In addition, we performed
periodic abdominal X-rays. Fecal samples were collected
from the patient every month and sent to the Yakult Central Institute for analysis of fecal bacterial flora and shortchain fatty acid content (13). To maintain strict anaerobic
conditions, the fecal samples were collected as soon as the
patient passed them and kept in an anaerobic clean bottle at
4°C. Prior to commencement of the synbiotics therapy, the
Digestive Diseases and Sciences, Vol. 46, No. 9 (September 2001)
patient’s fecal bacterial flora was quite abnormal, with very
few detectable anaerobic bacteria (Table 1). After 1 month
of synbiotics therapy, her feces contained a large number of
the administered probiotics and another species of bifidobacteria and lactobacilli (Table 1). The administered
bacteria, Bifidobacterium breve and Lactobacillus casei, were
distinguished from other species using two methods. The
first method is to use selective culture media, TCBPC agar
and LLV agar, which are suitable for the administered
Bifidobacterium breve and Lactobacillus casei to proliferate,
respectively. The second method is to ascertain whether or
not the colony forming bacteria are administered probiotics
by using monoclonal antibodies that specifically recognize
Bifidobacterium breve and Lactobacillus casei (11, 12). We
consider it very important to distinguish the probiotics from
other species of bifidobacteria and lactobacilli to verify that
the administered probiotics actually proliferated in the intestine to provide beneficial effects to the patient.
The levels of E. coli and Candida were very high in the
feces, more than 1 ⫻ 109 in 1.0 g wet feces, prior to
treatment. However, they gradually decreased after starting
the synbiotics therapy (Table 1). Furthermore, the ratio of
facultative anaerobic bacteria to total bacteria was very high
before the treatment, but their ratio was dramatically reduced after the synbiotics therapy (Table 1). These observations demonstrate that the ability of the intestine to
protect bacterial infections, the intestinal colonization resistance, was reinforced by synbiotics therapy.
The profile of fecal short-chain fatty acids was very abnormal before the synbiotics treatment. The levels of lactic
acid contents were very high compared to those of other
acids, such as acetate, propionate, and butyrate (Table 2).
Indeed, the level of lactate in the feces continued to be high
throughout the treatment periods (Table 2). However, the
patient never experienced severe acidosis after starting the
treatment. From this result, we believe that the large percentage of lactate in her feces after the commencement of
2011
2012
10.85
11.15
11.10
10.98
10.88
10.67
10.26
9.66
9.70
9.78
10.30
Before treatment
1
2
3
4
6
7
9
11
14
19
10.32
9.06
9.16
8.83
9.16
8.62
7.66
6.70
3.34
8.11
8.56
Facultative
anaerobic
bacteria
29.7
0.814
1.148
0.708
1.91
0.892
⬍0.01
⬍0.01
⬍0.01
2.14
1.82
Aerobes/total
bacteria (%)†
N.D.
4.43
7.20
8.60
9.49
N.D.
N.D.
N.D.
N.D.
N.D.
N.D.
Bacteroides
OF THE
N.D.
10.61
8.34
10.39
7.30
10.40
9.29
5.95
2.60
7.12
7.75
B.
breve
AND
N.D.
8.70
6.73
7.87
7.41
6.89
6.38
5.95
4.73
5.45
8.05
L. casei
FECES BEFORE
THE
6.91
11.04
10.90
10.19
9.25
9.00
8.48
7.48
7.65
9.30
9.74
OF
N.D.
9.02
9.07
9.37
9.03
9.20
9.78
9.39
8.99
8.88
8.62
Lactobacilli¶
COMMENCEMENT
Bifidobacteria‡
AFTER
9.20
8.43
8.35
7.97
8.08
7.82
7.35
6.58
3.00
8.09
7.90
E. coli
9.9
N.D.
8.27
7.88
8.68
6.99
N.D.
N.D.
2.78
7.13
8.09
Strepto and
enterococci
SYNBIOTICS*
2.78
N.D.
N.D.
N.D.
3.89
2.78
N.D.
N.D.
N.D.
N.D.
N.D.
Staphylococci
9.36
8.50
8.18
8.81
7.43
5.75
7.37
5.79
2.60
N.D.
2.60
Candida
*Bacterial number is expressed as log 10 per 1.0 g wet feces. N.D., corresponding bacteria were not detected In our culture system.
†Ratio of total facultative anaerobic bacteria to total bacteria. Total anaerobic bacteria were caliculated by serial dilution cultures of feces in VLM medium under strictly anaerobic
conditions. Total facultative anaerobic bacteria were also caliculated by serial dilution cultures in TSA medium.
‡Bifidobacteria other than administered B. breve, which were detected by culture in MNP medium.
¶Lactobacilli other than administered L. casei, which were detected by culture in LBS ager gel.
Total
bacteria
Treatment period
(months)
TABLE 1. BACTERIAL FLORA
KANAMORI ET AL
Digestive Diseases and Sciences, Vol. 46, No. 9 (September 2001)
A NOVEL SYNBIOTICS THERAPY
TABLE 2. SHORT-CHAIN FATTY ACIDS
IN THE
FECES BEFORE
AND
AFTER
THE
COMMENCEMENT
OF
SYNBIOTICS
Treatment period (months)
Lactate*
Acetate, propionate, and butyrate*
Lactate/acetate ⫹ propionate ⫹ butyrate
Before
treatment
1
2
3
4
6
7
9
11
14
19
47.54
16.22
2.93
62.60
73.30
0.85
12.09
33.48
0.45
103.45
64.78
1.60
19.06
34.33
0.56
84.24
96.33
0.87
127.44
64.09
1.99
85.44
8.65
9.88
50.40
53.20
0.95
6.50
6.50
0.065
0
36.52
0
*The short-chain fatty acids contents are given as ␮mol/1.0 g wet feces.
synbiotics was L-lactate that replaced D-lactate, which is
thought to cause severe lactic acidosis. The clinical course
of the patient after the introduction of synbiotics was very
satisfactory. She experienced a high fever attack soon after
starting synbiotics therapy, but after that initial episode, the
patient never suffered from either a high fever attack or
metabolic acidosis (Figure 1). Abdominal X-rays, taken
periodically, clearly showed that the abnormal intestinal
dilatation, seen in 1996 and 1997, gradually improved ac-
cording to the synbiotics therapy, suggesting a restoration of
her intestinal motility (Figure 2). The patient’s bowel movements were also restored after synbiotics therapy. Body
weight gain was dramatically accelerated after the commencement of therapy. The values of rapid turnover proteins (prealbumin, transferrin) (data not shown) and choline esterase in the serum increased in proportion to the
body weight gain, clearly demonstrating a nutritional improvement serologically (Figure 1). The patient became
Fig 2. Abdominal roentogenograms taken periodically from age 2 to age 5 years. Synbiotics therapy was introduced at the age of 3 years
3 months. Prominently dilated intestinal loops gradually disappeared after the commencement of start the synbiotics therapy. (a) Taken
at 2 years 4 months; (b) taken at 2 years 7 months; (c) taken at 3 years 3 months; (d) taken at 3 years 11 months; (e) taken at 4 years
6 months; (f) taken at 5 years 2 months.
Digestive Diseases and Sciences, Vol. 46, No. 9 (September 2001)
2013
KANAMORI ET AL
able to eat an ordinary diet with her parents, and after 1
year of therapy, she stopped taking an elementary formula
diet.
DISCUSSION
We have reported a case involving a patient with
short bowel syndrome that showed a dramatic improvement of intestinal function and motility through
the use of a newly designed synbiotics therapy.
Patients with short bowel syndrome often suffer
from high fever attacks in the late phase due to
central venous catheter sepsis and severe enterocolitis, which are often caused by bacterial overgrowth in
the dilated and dysmotile intestine. Catheter sepses
are considered to be induced not only by bacterial
invasion via the skin route, but also by bacterial
translocation from the intestinal lumen to the systemic circulation. This is especially true in patients
with short bowel syndrome (14). Bacterial translocations have been demonstrated in compromised patients with severe trauma (15) and in postoperative
patients (16). In addition, the bacterial overgrowth in
the dilated intestine is also accepted as a cause of
bacterial translocation. This pathological status is also
called bacterial overgrowth syndrome (17) and is often experienced in patients with short bowel syndrome (9, 10). Furthermore, the overgrown bacteria
may produce a large amount of D-lactate, which is
absorbed and results in D-lactate acidosis in patients
with short bowel syndrome (18 –20).
The patient reported here had suffered from repetitive high fever attacks and severe metabolic acidoses
upon reaching 2 years old, and her nutritional state
was quite deteriorated (Figure 1). She had no spontaneous bowel movement and she was dependent on
an enema every day. The fecal bacterial flora was
investigated for the presence of a pathogenic bacterial overgrowth in the intestine. The fecal bacterial
flora of the patient was demonstrated to be quite
abnormal, as shown in Table 1. Very few anaerobic
bacteria were detected, while facultative anaerobic
bacteria were detected at high levels in the patient.
This result is in contrast to the intestinal bacterial
flora in normal children at this age, which show an
anaerobic bacteria dominant profile (21). The ratio of
the number of total facultative anaerobic bacteria to
that of total bacterial is considered to be a useful
index to represent the protective ability of the intestine from bacterial infection. This protective ability is
called colonization resistance (22). This index in the
patient examined here was very high, suggesting that
she was very susceptible to enterocolitis (Table 1).
2014
From these clinical symptoms and abnormal intestinal bacterial flora, we concluded that the patient
suffered from the bacterial overgrowth syndrome, and
we decided to apply synbiotics therapy to the patient.
Currently, probiotics and prebiotics are widely accepted as a treatment for patients with antibiotic
induced diarrhea (3) and enterocolitis due to rota
virus infection (23) or other pathogenic organisms
(24). However, there are few reports that apply these
living bacteria to patients with intestinal failure. We
believe that patients with intestinal failure are good
candidates because they have been administered antibiotics very often and are frequently assigned a
restricted oral intake due to severe infection, and they
are expected to have quite abnormal bacterial flora
and suffer from the overgrowth of pathogenic bacteria
in the intestine. Indeed, some reports have commented that the selective decontamination of pathogenic bacteria by antibiotics in patients with bacterial
overgrowth syndrome was effective (25). However,
such an approach has a strong risk of producing
antibiotic-resistant bacteria, such as methycillinresistant Staphylococcus aureus and vancomycinresistant enterococcus (26). In contrast, probiotic and
prebiotic treatments aim to regulate bacterial overgrowth by several mechanisms, such as the competition for nutrients between bacteria and the production of antibacterial substances (1–3). These
sophisticated regulatory systems produced by probiotics are expected to be more beneficial to seriously ill
patients.
Many probiotics are used throughout the world,
such as Bifidobacterium, Lactobacillus, Streptococcus,
and Saccharomyces (1–3, 5, 7, 8). Among these bacteria, we adopted two living bacteria for use here,
Bifidobacterium breve and Lactobacillus casei. These
bacterial species were established several decades ago
at the Yakult Central Institute and have a relatively
long history of application to humans. Moreover, they
are thought to be very safe bacteria because no severe
complications have been reported. In addition, their
use has a specific advantage in that they have specific
monoclonal antibodies that are used for their detection by immunological techniques (11, 12). In our
patient, the administered probiotics were easily detected at high levels in the feces. From these data, we
strongly suggest that the probiotics therapy truly affected the intestinal functions.
Various desirable effects of probiotics on the host
have been reported. Probiotics have the ability to
suppress the proliferation of pathogenic bacteria by
nutrient competition and to produce large amounts of
Digestive Diseases and Sciences, Vol. 46, No. 9 (September 2001)
A NOVEL SYNBIOTICS THERAPY
short-chain fatty acids in the intestine. Short-chain
fatty acids have been demonstated to possess many
beneficial effects for the intestinal epithelium and
intestinal motility (27, 28). Furthermore, the probiotics are believed potentially to upregulate the immune
system, especially for resistance to bacterial infection
(1–3).
In the case reported here, the nutritional state of
the patient was dramatically improved (Fig. 1), and
the pathogenic bacterial overgrowth in the intestine
was suppressed (Table 1). Two years after the synbiotics therapy, the patient’s fecal bacterial flora was
anaerobic bacteria dominant, and the proliferation of
pathogenic bacteria, such as E. coli and Candida, was
suppressed (Table 1). These beneficial effects were
attained through improvement of the intestinal motility and through upregulation of the intestinal immune system through the actions of the probiotics, as
described in this section.
The galactooligosaccharides not only were a substrate for the administered bacteria, but also were a
good substrate for the few residing bifidobacteria and
lactobacilli in the intestine because many bifidobacteria and lactobacilli species other than these administered probiotics were detected in the feces after the
synbiotics therapy. Therefore, administered galactooligosaccharides also played a very important role as a
prebiotic in the improvement of the intestinal function of the patient.
Short-chain fatty acids, such as acetate, propionate,
and butyrate, are thought to play various important
roles in in the large bowel. They are thought to
stimulate proliferation of the intestinal epithelium
(29), to stimulate intestinal motility (30), and to stimulate excretion of pancreatic enzymes (31). These
short-chain fatty acids are the end products of the
normal bacterial fermentation of carbohydrates arriving in the large bowel (27). If the fermentation of
carbohydrates by intestinal bacteria is impaired, acetate, propionate, and butyrate levels decrease in the
intestine, whereas the levels of intermediate products
of impaired fermentation, such as lactate, increase.
This increase in intermediate products results in the
induction of various undesirable conditions. In the
case reported here, the feces of the patient contained
very high levels of lactate before and after the synbiotics therapy (Table 2). These high levels of lactate
suggested that the impaired fermentation of the unabsorbed carbohydrates continued in the colon by the
colonic-residing bacteria. However, the increased levels of lactate produced in the colon after synbiotic
treatment might consist of L-lactate rather than DDigestive Diseases and Sciences, Vol. 46, No. 9 (September 2001)
lactate. We suggest this switch from two observations.
First, the severe acidosis that was experienced often
before treatment was never experienced after treatment. Second, Bifidobacterium breve and Lactobacillus casei are known to produce L-lactate only (data
not shown), and these administered bacteria resided
very efficiently in the colon of the patient. Additionally, judging from our case, L-lactate does not seem to
have the same adverse effects to the intestinal function as D-lactate, even though it, exists at high levels in
the intestinal lumen.
Together, these results suggest that the synbiotic
therapy designed by us, using the two types of probiotics (Bifidobacterium brevs and Lactobacillus casei)
and the prebiotic (galactooligosaccharides), is a very
effective and promising treatment for patients with
short bowel syndrome.
REFERENCES
1. Fuller R: Probiotics in human medicine. Gut 32:439 – 442, 1991
2. Fuller R, Gibson R: Modification of the intestinal microflora
using probiotics and prebiotics. Scand J Gastroenterol 32
(Suppl 222):28 –31, 1997
3. Vanderhoof JA, Young RJ: Use of probiotics in childhood
gastrointestinal disorders. J Pediatr Gastroenterol Nutr
27:323–332, 1998
4. Lilly D, Stillwell RJ: Probiotics; Growth promoting factors
produced by microorganisms. Science 147:747–748, 1965
5. Fuller R: A review: Probiotics in man and animals. J Appl
Bacteriol 66:365–378, 1989
6. Gibson GR, Beatty ER, Wang X, Cummings JH: Selective
stimulation of Bifidobactera in the human colon by oligofructose and inulin. Gastroenterology 108:975–982, 1995
7. Gibson GR, Roberfroid MB: Dietary modulation of the human
colonic microbiota: Introducing the concept of prebiotics. J
Nutr 125:1401–1412, 1995
8. Colins MD, Gibson GR: Probiotics, prebiotics, and synbiotics:
Approaches for modulating the microbial ecology of the gut.
Am J Clin Nutr 69 (Suppl):1052S–1057S, 1999
9. Kaufman SS, Loseke CA, Lupo JV, Young RJ, Murray ND,
Pinch LW, Vanderhoof JA: Influence of bacterial overgrowth
and intestinal inflammation on duration of parenteral nutrition
in children with short bowel syndrome. J Pediatr 131:356 –361,
1997
10. Vanderhoof JA, Young RJ, Murray N, Kaufman SS: Treatment strategies for small bowel overgrowth in short bowel
syndrome. J Pediatr Gastroenterol Nutr 27:155–160, 1998
11. Kitajima H, Sumia Y, Tanaka R, Yuki N, Takayama H, Fujimura M: Early administration of Bifidobacterum breve to
preterm infants: Randomised controlled trial. Arch Dis Child
76:101–107, 1997
12. Yuki N, Watanabe K, Mike A, Tagami Y, Tanaka R, Ohwaki
M, Morotomi M: Survival of a probiotic, Lactobacillus casei
strain Shirota, in the gastrointestinal tract: Selective isolation
from faeces and identification using monoclonal antibodies. Int
J Food Microbiol 48:51–57, 1999
13. Chonan O, Matsumoto K, Watanuki M: Effect of galactooli-
2015
KANAMORI ET AL
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
gosaccharides on calcium absorption and preventing bone loss
in ovariectimized rats. Biosci Biotech Biochem 59:236 –239,
1995
Kukchubasche AG, Smith SD, Rowe MI: Catheter sepsis in
short-bowel syndrome. Arch Surg 127:21–24, 1992
Brathwalt CEM, Ross CE, Nagele R: Bacterial translocation
occurs in humans after traumatic injury: Evidence using immunofluorescence. J Trauma 34:586 –590, 1993
MacFie J, O’Boyle C, Mitchell CJ, Johnstone DJ, Sudworth P:
Gut origin of sepsis: A prospective study investigating association between bacterial translocation, gastric microflora, and
septic morbidity. Gut 45:223–228, 1999
Sherman P, Lichtman S: Small bowel bacterial overgrowth
syndrome. Dig Dis 5:157–171, 1987
Oh MS, Phelps KR, Traube M, Barbosa-Saldivar JL, Boxhill C,
Carroll HJ: D-lactic acidosis in a man with the short-bowel
syndrome. Engl J Med 301:249 –252, 1979
Cardarini MI, Pons S, D’Agostino D, Depaula JA, Greco G,
Negri G, Ascione A, Bustos D: Abnormal fecal flora in a
patient with short bowel syndrome. An in vitro study on effect
of pH on D-lactic acid production. Dig Dis Sci 41:1649 –1652,
1996
Bongaerts GPA, Tolboom JJM, Naber AHJ, Sperl WJK,
Severijnen RSVM, Bakkeren JAJM, Willems JL: Role of bacteria in the pathogenesis of short bowel syndrome-associated
D-lactic acidemia. Microbial Pathogen 22:285–293, 1997
Simon GL, Gorbach SL: Intestinal flora in health and disease.
Gastroenterology 86:174 –193, 1984
Van der Waaij, Berghuis-De Vries JM, Lekkerkerk-Van der
Wees: Colonization resistance of the digestive tract in conventional and antibiotic-treated mice. J Hyg 69:405– 411, 1971
Majamaa H, Isolauri E, Saxelin M, Vesikari T: Lactic acid
bacteria in the treatment of acute rotavirus gastroenteritis.
J Pediatr Gastroenterol Nutr 20:333–338, 1995
Mitra AK, Rabbani GH: A double-blind, controlled trial of
2016
25.
26.
27.
28.
29.
30.
31.
Bioflorin(Streptococcus faecium SF68) in adults with acute
diarrhea due to Vibrio cholerae and enterotoxigenic Escherichia coli. Gastroenterology 99:1149 –1152, 1990
Spath G, Hirner A: Microbial translocation and impairment of
mucosal immunity induced by an elemental diet in rats is
prevented by selective decontamination of the digestive tract.
Eur J Surg 164:223–228, 1998
Jumaa PA, Hateley PM, Tabaqchali S: Methicillin-resistant
Stapyhlococcus aureus and vancomycin-resistant enterococci.
Lancet 350:738 –739, 1997
Macfarlane GT, Gibson GR: Microbiological aspects of the
production of short-chain fatty acids in the large bowel. In
Physiological and Clinical Aspect of Short-Chain Fatty Acids,
JH Cummings, JL Rombeau T Sakata (eds). Cambridge, Cambridge University Press, 1995, pp 88 –106
Livesey G, Elia M: Short-chain fatty acids as an energy source
in the colon: Metabolism and clinical implications. In Physiological and Clinical Aspect of Short-Chain Fatty Acids, JH
Cummings, JL Rombeau, T Sakata (eds). Cambridge, Cambridge University Press, 1995, pp 427– 482
Cherbut C: Effects of short-chain fatty acids on gastrointestinal
motility. In Physiological and Clinical Aspect of Short-Chain
Fatty Acids, JH Cummings, JL Rombeau, T Sakata (eds).
Cambridge, Cambridge University Press, 1995, pp 191–208
Sakata T: Effects of short-chain fatty acids on the proliferation
of gut epithelial cells in vivo. In Physiological and Clinical
Aspect of Short-Chain Fatty Acids, JH Cummings, JL Rombeau, T Sakata (eds). Cambridge, Cambridge University Press,
1995, pp 289 –305
Katoh K: Effects of short-chain fatty acids on exocrine and
endocrine pancreatic secretion. In Physiological and Clinical
Aspect of Short-Chain Fatty Acids, JH Cummings, JL Rombeau, T Sakata (eds). Cambridge, Cambridge University Press,
1995, pp 222–242
Digestive Diseases and Sciences, Vol. 46, No. 9 (September 2001)