Fecal flora in different populations, special reference to diet1’ 2 Sydney
M.
Finegold,3
M.D.
and
Vera
L. Sutter,4
ABSTRACT
Although
potent
fecal
changes
in
microflora,
comparison. metabolic is clean
It may activity, that
quantitative
be, however, particularly
significant changes
ohogical observations
Ph.D.
antimicrobial
diet
on that
agents
dietary even
in terms
changes
may
with
may
supplements such
minor in
in the fecal microflora.
research
result
activity
mucosa-associated
31: S1h6-S122,
flora
at different
levels,
diets
Attebery et al. (4) studied three subjects over a 9-day period on an elemental diet consisting of amino acids, glucose, safflower oil, emulsifier, vitamins, and electrolytes. During the 9-day period, the subjects had from three to five bowel movements, each of a somewhat smaller volume than usual, but unchanged in odor, color, or consistency. Since bacteria account for a significant portion of the volume of feces, it is clear that there was a significant reduction in flora asSh16
The American
hong-term
dietary
changes
in
or cocarcinogens. major
It
qualitative
explain
the
on
epidemi-
be studies of the flora
and small bowel), studies.
in by
Am.
I
studies of Clin.
Nutr.
1978.
Recent epidemiological studies associate colon cancer with specific types of diet. In general, highly developed countries have a high incidence of colon cancer, and less well developed countries have a how incidence. Japan represents an exception in that it is highly developed but has a low incidence of large bowel cancer. Japanese who adopt a Western diet, however, develop colon cancer with increased frequency; among Japanese immigrants, the frequency approaches that of native Americans (1). There has also been interest in the possibility that a vegetarian diet (2) or a diet rich in wheat fiber (3) might protect against colon cancer. This paper summarizes a number of studies on the fecal microbial flora in different populations, with emphasis on the role of diet and diet supplements. Elemental
help
diet and colon cancer would and
changes changes
in significant
without
that might
significant modest
carcinogens
at different levels of the gastrointestinal tract (particularly the cecum the
and
produce
may
of possible
metabolic
Other
of the association between
rapid
usually changes
of production occur
effect
Journal
of Clinical
Nutrition
Downloaded from https://academic.oup.com/ajcn/article-abstract/31/10/S116/4656075 by University of Glasgow user on 01 August 2018
sociated with the intake of the elemental diet. Transit time was prolonged in all individuals. In addition to the decrease in flora, some qualitative changes in flora occurred. Extremely oxygen-sensitve anaerobes, accounting for 15 to 20% of the total anaerobes in the control specimens, disappeared completely from all individuals during the experimental diet; these organisms again accounted for 15 to 20% of the total anaerobes in postexperimental diet specimens. There was some increase in count of coliforms and a decrease in certain gram-positive organisms including Clostridium perfringens (but with appearance of other clostridia), Bifidobacterium, anaerobic gram-positive cocci, and Lactobacillus. Crowther et at. (5) studied three subjects over a 10-day period on a chemically defmed diet. Transit time was prolonged. Enterococci disappeared, but the balance of the flora remained unchanged. These authors noted no conversion of cholesterol to its metabolites. ‘From the Medical Service and Anaerobic Bacteriology Research Laboratory, Wadsworth Hospital Center, Veterans Administration, Los Angeles, California 90073, and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024. 2Address reprint requests to: Dr. S. M. Finegold, Infectious Disease Section, Wadsworth Veterans Administration Hospital, Los Angeles, California 90073. 3Chief, Infectious Disease Section, Wadsworth V.A. Hospital. Director, Anaerobic Bacteriology Research Laboratory, Wadsworth V. A. Hospital.
31: OCTOBER
1978,
pp. S1l6-S122.
Printed
in U.S.A.
FECAL
FLORA
Bornside and Cohn (6) also noted no significant differences in fecal microflora on a chemically defmed how-residue liquid diet.
Lactubose is a bulking and acidifying agent used in the treatment of hepatic coma. Vince et al. (7) studied five patients with hepatic encephalopathy on a diet containing added lactubose for a period of 2 to 3 weeks. The amount of lactulose was adjusted to give two to three soft stools per day. Two of the three subjects who initially showed clostridia in their stools had reduced numbers of clostridia during the time that they were on lactulose. Most other organisms were not affected. differing
risks
of
Aries et al. (8) noted significantly more bacteroides and bifidobacteria in feces from English subjects than in specimens from Ugandans. This group (9) later reported on a large number of specimens from high-risk subjects (British and American) and low-risk subjects (Ugandans, Indians, and Japanese). Feces from the high-risk populations yielded many more bacteroides whereas the low-risk group had many more aerobic streptococci and enterobacteria. English subjects had a much higher percentage of Streptococcus faeca/is among the enterococci than the Indian subjects. A later paper from this group (10) indicated that subjects from countries consuming a Western-type diet appeared to have a larger proportion of gram-negative anaer-
TABLE Significant flora
diet
DIET
S1h7
obes (bacteroides and fusobacteria) and that subjects from countries with a low-risk of colon cancer had a larger proportion of grampositive organisms (including a statistically significant increase in eubacteria). Hill (11) noted that steroid nuclear-dehydrogenating clostridia (the C/ostridium paraputrflcum group) were found in larger numbers in stools of British and Americans than of people from countries with a low incidence of bowel cancer. A still later paper from this group (12) again noted that C. paraputr/Icum was common in stool samples from England, Scothand, Wales, and the United States but rare in samples from Uganda and Japan; however, subjects from Hong Kong, where the mcidence of colon cancer is relatively high, yielded only small numbers of C. paraputrificum, most of which were not able to dehydrogenate the steroid nucleus. Our group (1) studied two groups of Japanese-Americans living in the Los Angeles area. One group ate a primarily traditional Japanese diet, and the other group ate a primarily Western diet. There were a number of differences in fecal flora that were statistically significant (Table 1) but, considering the large number of organisms tested, some of the differences that were noted may have occurred by chance alone. There were no significant differences with regard to the C. paraputrflcum group of organisms (Table 2). We (13) have also studied the fecal flora of patients with multiple adenomatous colonic polyps (a group with a high risk of developing colon cancer) and matched control subjects without polyps; both groups consumed a typ-
Lactulose
Studies of populations with developing colon cancer
AND
1 differences
in fecal
study
Age S. faecahis var. faecahis Other facultative or aerobic organisms Eubacterium contortum Eubacterium lentum BVldobacterium infantis, other Peptrostreptococcus sp. 1 Peptnostreptococcus sp. 1-25 “Twenty specimens analysis (Fisher’s exact organisms/g of feces.
from 15 subjects. probability statistic).
Japanese diet
western diet’
603d
413d
Twenty specimens d Years (mean).
Downloaded from https://academic.oup.com/ajcn/article-abstract/31/10/S116/4656075 by University of Glasgow user on 01 August 2018
from e
18 subjects. Confirmed by
value
0.013! 0.038e 106/g.
P 0.04c Vegetarian Nonvegetanian p o.io 2 present 8 present
P 0.04c Vegetarian Nonvegetanian
P 0.04
peptostreptococci
“ These analyses 5% level. bLow and nonvegetanian
P #{216}#{216}5C Vegetarian Nonvegetarian P 0.09
3.4 mean 6.0 mean
Low-high’
P 0.10
be needed difference
for significance at the between the vegetarian
group Vegetarian No.
of
Nonvegetarian
SDA”
No.
subjects-49
NonSDA
SDA
N o. ofsubjects-31
of subjects-45
F’ No. harboring
6 0 0 9 7 2 0 3 21
C. butyricum C. cadaveris C. indolis C. innocuum C. paraputrficum C. sartagoformum C. septicum C. tertium Total group
dry
“Seventh-Day feces (rounded
Adventist. off to the
Range
Converted mean
5-10
3.3
8-10 4-9 4-6 4-8 4-10 bp
nearest
No. harbor. ing
0 0 4.1 3.5 2.4 0 2.7 5.0
4 1 0 12 4 0 0 2 17
Range
4-11 10
had higher counts and a greater of these two organisms. Table 7 shows the significant differences in fecal flora between nonvegetarian Adventists and other nonvegetarians previously studied by our group. Table 8 shows the converted mean counts of major fecal flora components in various groups studied in our laboratory. Of particular interest is the much higher mean count of lactobacilli in the Adventist population and the much lower incidence of
8-9 4-12
Downloaded from https://academic.oup.com/ajcn/article-abstract/31/10/S116/4656075 by University of Glasgow user on 01 August 2018
Range
3.2 0 3.2 2.8 2.7 2.6 2.9 4.1 5.0
10 4-9 8 4-7 7 4-10 4-10
2 2 7 15 ‘Log,o
no.
and fusobactena as compared
of starvation
Con verted mean
6-9
3 0 1 3 1
of variance.
C. perfringens tist population studied. Effect
No. harboring
3.2 2.6 0 4.2 3.1 0 0 2.8 4.9
3-12 5-10
value based on one-way analysis log in the case of range).
Adventists incidence
Converted mean
on fecal
of organisms
0.964 0.4 14 0.221 0.135 0.376 0.367 0.046 0.011 0.974 pen g of
in the Advenwith the others
flora
Unpublished studies by our group (in collaboration with Ernst Drenick) on a small group of subjects on total starvation yielded interesting results. These individuals had only a very small bowel movement once every 30
FINEGOLD
S120
AND
(17), 10 volunteers received various dietary supplements including different sources of dietary fiber (pectin, guar, plantains, and other bananas) and, in view of the evidence incriminating a high fat intake with colon cancer, olive oil and medium-chain triglycerides. Each dietary period lasted 2 weeks. They detected no significant difference in the composition of the fecal flora with any of the alterations in diet. Walters et al. (18) fed volunteers fiber supplements from wheat bran and bagasse for 12-week periods. Stool weight and stool fat excretion increased on both dietary fiber supplements. Bagasse increased the daily loss of bile acids but bran did not. Decreased transit time without alter-
days or so. Thus there is a remarkable reduction in the intestinal flora, but it is interesting to note that the small amount of feces that is produced monthly is qualitatively and quantitatively similar to control specimens in these subjects when they were on a standard diet. Effect
of dietary
Drasar et a high-fiber 3 weeks of There was weight and time but no terial flora.
fiber
on fecal
flora
al. (3) placed four volunteers on diet (bran) for 3 weeks, following study on a conventional diet. a significant increase in stool a significant decrease in transit significant change in fecal bacIn a study by Drasar and Jenkins
TABLE 7 Significant” differences nonvegetarian Adventists studied nonvegetanians5
SUTTER
in fecal flora between and previously
Converted Organism
Escherichia
6.51 4.67 10.14 6.64 7.43 6.63 5.85 11.68 3.07
pneumoniae
All Lactobacillus Lactobacillus acidophilus Lactobacillus plantarum Peptostreptococcus productus Ruminococcus sp. 1 All Bacteroides C. perfringens “Significant at the 5% level on less previously found significant by one-way diet group and polyp control group.
TABLE Converted in various
Polyp controls (25 subjects)
Nonvegetarian (14 subjects)
coli
Klebsiella
mean counts diet groups
of major
8.34 3.36 4.51 4.45 0.0 4.66 0.0 11.04 5.13
8.10 0.0 6.90 4.15 4.16 3.96 0.0 10.81 4.93
by Duncan’s new analysis of variance.
fecal
flora
multiple is
range test. Nonvegetarians
.
,
This is a subset previously studied
of the fecal flora include Western
components
Conventional .,, U.S. diet
Seventh-Day Adventist Log,
E.coli Enterococci Other streptococci Bacillus Lactobacillus Bacteroidesfragilis Fusobactenium Eubactenium Bifidobactenium Clostnidium
8
5
cocci controls.
9 “Includes
vegetarians
number
7 6 8 4 10 11
M.
Finegold,3
M.D.
and
Vera
L. Sutter,4
ABSTRACT
Although
potent
fecal
changes
in
microflora,
comparison. metabolic is clean
It may activity, that
quantitative
be, however, particularly
significant changes
ohogical observations
Ph.D.
antimicrobial
diet
on that
agents
dietary even
in terms
changes
may
with
may
supplements such
minor in
in the fecal microflora.
research
result
activity
mucosa-associated
31: S1h6-S122,
flora
at different
levels,
diets
Attebery et al. (4) studied three subjects over a 9-day period on an elemental diet consisting of amino acids, glucose, safflower oil, emulsifier, vitamins, and electrolytes. During the 9-day period, the subjects had from three to five bowel movements, each of a somewhat smaller volume than usual, but unchanged in odor, color, or consistency. Since bacteria account for a significant portion of the volume of feces, it is clear that there was a significant reduction in flora asSh16
The American
hong-term
dietary
changes
in
or cocarcinogens. major
It
qualitative
explain
the
on
epidemi-
be studies of the flora
and small bowel), studies.
in by
Am.
I
studies of Clin.
Nutr.
1978.
Recent epidemiological studies associate colon cancer with specific types of diet. In general, highly developed countries have a high incidence of colon cancer, and less well developed countries have a how incidence. Japan represents an exception in that it is highly developed but has a low incidence of large bowel cancer. Japanese who adopt a Western diet, however, develop colon cancer with increased frequency; among Japanese immigrants, the frequency approaches that of native Americans (1). There has also been interest in the possibility that a vegetarian diet (2) or a diet rich in wheat fiber (3) might protect against colon cancer. This paper summarizes a number of studies on the fecal microbial flora in different populations, with emphasis on the role of diet and diet supplements. Elemental
help
diet and colon cancer would and
changes changes
in significant
without
that might
significant modest
carcinogens
at different levels of the gastrointestinal tract (particularly the cecum the
and
produce
may
of possible
metabolic
Other
of the association between
rapid
usually changes
of production occur
effect
Journal
of Clinical
Nutrition
Downloaded from https://academic.oup.com/ajcn/article-abstract/31/10/S116/4656075 by University of Glasgow user on 01 August 2018
sociated with the intake of the elemental diet. Transit time was prolonged in all individuals. In addition to the decrease in flora, some qualitative changes in flora occurred. Extremely oxygen-sensitve anaerobes, accounting for 15 to 20% of the total anaerobes in the control specimens, disappeared completely from all individuals during the experimental diet; these organisms again accounted for 15 to 20% of the total anaerobes in postexperimental diet specimens. There was some increase in count of coliforms and a decrease in certain gram-positive organisms including Clostridium perfringens (but with appearance of other clostridia), Bifidobacterium, anaerobic gram-positive cocci, and Lactobacillus. Crowther et at. (5) studied three subjects over a 10-day period on a chemically defmed diet. Transit time was prolonged. Enterococci disappeared, but the balance of the flora remained unchanged. These authors noted no conversion of cholesterol to its metabolites. ‘From the Medical Service and Anaerobic Bacteriology Research Laboratory, Wadsworth Hospital Center, Veterans Administration, Los Angeles, California 90073, and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024. 2Address reprint requests to: Dr. S. M. Finegold, Infectious Disease Section, Wadsworth Veterans Administration Hospital, Los Angeles, California 90073. 3Chief, Infectious Disease Section, Wadsworth V.A. Hospital. Director, Anaerobic Bacteriology Research Laboratory, Wadsworth V. A. Hospital.
31: OCTOBER
1978,
pp. S1l6-S122.
Printed
in U.S.A.
FECAL
FLORA
Bornside and Cohn (6) also noted no significant differences in fecal microflora on a chemically defmed how-residue liquid diet.
Lactubose is a bulking and acidifying agent used in the treatment of hepatic coma. Vince et al. (7) studied five patients with hepatic encephalopathy on a diet containing added lactubose for a period of 2 to 3 weeks. The amount of lactulose was adjusted to give two to three soft stools per day. Two of the three subjects who initially showed clostridia in their stools had reduced numbers of clostridia during the time that they were on lactulose. Most other organisms were not affected. differing
risks
of
Aries et al. (8) noted significantly more bacteroides and bifidobacteria in feces from English subjects than in specimens from Ugandans. This group (9) later reported on a large number of specimens from high-risk subjects (British and American) and low-risk subjects (Ugandans, Indians, and Japanese). Feces from the high-risk populations yielded many more bacteroides whereas the low-risk group had many more aerobic streptococci and enterobacteria. English subjects had a much higher percentage of Streptococcus faeca/is among the enterococci than the Indian subjects. A later paper from this group (10) indicated that subjects from countries consuming a Western-type diet appeared to have a larger proportion of gram-negative anaer-
TABLE Significant flora
diet
DIET
S1h7
obes (bacteroides and fusobacteria) and that subjects from countries with a low-risk of colon cancer had a larger proportion of grampositive organisms (including a statistically significant increase in eubacteria). Hill (11) noted that steroid nuclear-dehydrogenating clostridia (the C/ostridium paraputrflcum group) were found in larger numbers in stools of British and Americans than of people from countries with a low incidence of bowel cancer. A still later paper from this group (12) again noted that C. paraputr/Icum was common in stool samples from England, Scothand, Wales, and the United States but rare in samples from Uganda and Japan; however, subjects from Hong Kong, where the mcidence of colon cancer is relatively high, yielded only small numbers of C. paraputrificum, most of which were not able to dehydrogenate the steroid nucleus. Our group (1) studied two groups of Japanese-Americans living in the Los Angeles area. One group ate a primarily traditional Japanese diet, and the other group ate a primarily Western diet. There were a number of differences in fecal flora that were statistically significant (Table 1) but, considering the large number of organisms tested, some of the differences that were noted may have occurred by chance alone. There were no significant differences with regard to the C. paraputrflcum group of organisms (Table 2). We (13) have also studied the fecal flora of patients with multiple adenomatous colonic polyps (a group with a high risk of developing colon cancer) and matched control subjects without polyps; both groups consumed a typ-
Lactulose
Studies of populations with developing colon cancer
AND
1 differences
in fecal
study
Age S. faecahis var. faecahis Other facultative or aerobic organisms Eubacterium contortum Eubacterium lentum BVldobacterium infantis, other Peptrostreptococcus sp. 1 Peptnostreptococcus sp. 1-25 “Twenty specimens analysis (Fisher’s exact organisms/g of feces.
from 15 subjects. probability statistic).
Japanese diet
western diet’
603d
413d
Twenty specimens d Years (mean).
Downloaded from https://academic.oup.com/ajcn/article-abstract/31/10/S116/4656075 by University of Glasgow user on 01 August 2018
from e
18 subjects. Confirmed by
value
0.013! 0.038e 106/g.
P 0.04c Vegetarian Nonvegetanian p o.io 2 present 8 present
P 0.04c Vegetarian Nonvegetanian
P 0.04
peptostreptococci
“ These analyses 5% level. bLow and nonvegetanian
P #{216}#{216}5C Vegetarian Nonvegetarian P 0.09
3.4 mean 6.0 mean
Low-high’
P 0.10
be needed difference
for significance at the between the vegetarian
group Vegetarian No.
of
Nonvegetarian
SDA”
No.
subjects-49
NonSDA
SDA
N o. ofsubjects-31
of subjects-45
F’ No. harboring
6 0 0 9 7 2 0 3 21
C. butyricum C. cadaveris C. indolis C. innocuum C. paraputrficum C. sartagoformum C. septicum C. tertium Total group
dry
“Seventh-Day feces (rounded
Adventist. off to the
Range
Converted mean
5-10
3.3
8-10 4-9 4-6 4-8 4-10 bp
nearest
No. harbor. ing
0 0 4.1 3.5 2.4 0 2.7 5.0
4 1 0 12 4 0 0 2 17
Range
4-11 10
had higher counts and a greater of these two organisms. Table 7 shows the significant differences in fecal flora between nonvegetarian Adventists and other nonvegetarians previously studied by our group. Table 8 shows the converted mean counts of major fecal flora components in various groups studied in our laboratory. Of particular interest is the much higher mean count of lactobacilli in the Adventist population and the much lower incidence of
8-9 4-12
Downloaded from https://academic.oup.com/ajcn/article-abstract/31/10/S116/4656075 by University of Glasgow user on 01 August 2018
Range
3.2 0 3.2 2.8 2.7 2.6 2.9 4.1 5.0
10 4-9 8 4-7 7 4-10 4-10
2 2 7 15 ‘Log,o
no.
and fusobactena as compared
of starvation
Con verted mean
6-9
3 0 1 3 1
of variance.
C. perfringens tist population studied. Effect
No. harboring
3.2 2.6 0 4.2 3.1 0 0 2.8 4.9
3-12 5-10
value based on one-way analysis log in the case of range).
Adventists incidence
Converted mean
on fecal
of organisms
0.964 0.4 14 0.221 0.135 0.376 0.367 0.046 0.011 0.974 pen g of
in the Advenwith the others
flora
Unpublished studies by our group (in collaboration with Ernst Drenick) on a small group of subjects on total starvation yielded interesting results. These individuals had only a very small bowel movement once every 30
FINEGOLD
S120
AND
(17), 10 volunteers received various dietary supplements including different sources of dietary fiber (pectin, guar, plantains, and other bananas) and, in view of the evidence incriminating a high fat intake with colon cancer, olive oil and medium-chain triglycerides. Each dietary period lasted 2 weeks. They detected no significant difference in the composition of the fecal flora with any of the alterations in diet. Walters et al. (18) fed volunteers fiber supplements from wheat bran and bagasse for 12-week periods. Stool weight and stool fat excretion increased on both dietary fiber supplements. Bagasse increased the daily loss of bile acids but bran did not. Decreased transit time without alter-
days or so. Thus there is a remarkable reduction in the intestinal flora, but it is interesting to note that the small amount of feces that is produced monthly is qualitatively and quantitatively similar to control specimens in these subjects when they were on a standard diet. Effect
of dietary
Drasar et a high-fiber 3 weeks of There was weight and time but no terial flora.
fiber
on fecal
flora
al. (3) placed four volunteers on diet (bran) for 3 weeks, following study on a conventional diet. a significant increase in stool a significant decrease in transit significant change in fecal bacIn a study by Drasar and Jenkins
TABLE 7 Significant” differences nonvegetarian Adventists studied nonvegetanians5
SUTTER
in fecal flora between and previously
Converted Organism
Escherichia
6.51 4.67 10.14 6.64 7.43 6.63 5.85 11.68 3.07
pneumoniae
All Lactobacillus Lactobacillus acidophilus Lactobacillus plantarum Peptostreptococcus productus Ruminococcus sp. 1 All Bacteroides C. perfringens “Significant at the 5% level on less previously found significant by one-way diet group and polyp control group.
TABLE Converted in various
Polyp controls (25 subjects)
Nonvegetarian (14 subjects)
coli
Klebsiella
mean counts diet groups
of major
8.34 3.36 4.51 4.45 0.0 4.66 0.0 11.04 5.13
8.10 0.0 6.90 4.15 4.16 3.96 0.0 10.81 4.93
by Duncan’s new analysis of variance.
fecal
flora
multiple is
range test. Nonvegetarians
.
,
This is a subset previously studied
of the fecal flora include Western
components
Conventional .,, U.S. diet
Seventh-Day Adventist Log,
E.coli Enterococci Other streptococci Bacillus Lactobacillus Bacteroidesfragilis Fusobactenium Eubactenium Bifidobactenium Clostnidium
8
5
cocci controls.
9 “Includes
vegetarians
number
7 6 8 4 10 11
