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Factors Related to Colonization with Oxalobacter formigenes in U.S. Adults

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To elucidate the determinants of Oxalobacter formigenes colonization in humans. O. formigenes is a gram-negative anaerobic bacterium that colonizes the colon of a substantial proportion of the normal population and metabolizes dietary and endogenous oxalate. The bacterium has been associated with a large reduction in the odds of recurrent calcium oxalate kidney stones. Subjects were 240 healthy individuals from Massachusetts and North Carolina. O. formigenes was detected by culture of fecal swabs. Information on factors of interest was obtained by telephone interviews and self-administered questionnaires. The overall prevalence of O. formigenes was 38%. Use of specific antibiotics previously thought to affect the bacterium was significantly related to colonization, with prevalences of 17%, 27%, and 36%, for those who had used these drugs <1, 1-5, and >5 years ago, compared with 55% in nonusers. There were no significant associations with demographic factors, nutrient intake, or medical history, although the prevalence appeared to increase somewhat with increasing oxalate consumption. Some antibiotics markedly affect colonization with O. formigenes. Although no other factor was identified as having a material influence on the prevalence of the bacterium, there is much to learn about how an individual acquires the organism and which factors affect persistence of colonization.
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Factors Related to Colonization
with Oxalobacter formigenes in U.S. Adults
Judith Parsells Kelly, M.S.,
1
Gary C. Curhan, M.D., Sc.D.,
2
David R. Cave, M.D., Ph.D.,
3
Theresa E. Anderson, R.N.,
1
and David W. Kaufman, Sc.D.
1
Abstract
Goals: To elucidate the determinants of Oxalobacter formigenes colonization in humans.
Background: O. formigenes is a gram-negative anaerobic bacterium that colonizes the colon of a substantial pro-
portion of the normal population and metabolizes dietary and endogenous oxalate. The bacterium has been
associated with a large reduction in the odds of recurrent calcium oxalate kidney stones. Subjects were 240 healthy
individuals from Massachusetts and North Carolina. O. formigenes was detected by culture of fecal swabs. In-
formation on factors of interest was obtained by telephone interviews and self-administered questionnaires.
Study Results: The overall prevalence of O. formigenes was 38%. Use of specific antibiotics previously thought to
affect the bacterium was significantly related to colonization, with prevalences of 17%, 27%, and 36%, for those
who had used these drugs <1, 1–5, and >5 years ago, compared with 55% in nonusers. There were no significant
associations with demographic factors, nutrient intake, or medical history, although the prevalence appeared to
increase somewhat with increasing oxalate consumption.
Conclusions: Some antibiotics markedly affect colonization with O. formigenes. Although no other factor was
identified as having a material influence on the prevalence of the bacterium, there is much to learn about how an
individual acquires the organism and which factors affect persistence of colonization.
Introduction
In recent years there has been increasing interest in ex-
ploring the probiotic potential of intestinal microbiota.
1,2
A
promising example is Oxalobacter formigenes, a gram-negative,
obligately anaerobic bacterium that inhabits the mamma-
lian colon.
3
The genome has been fully sequenced by the
Broad Institute in Boston (www.broad.mit.edu=annotation=
genome=oxalobacter_group). O. formigenes is unique in that
dietary and endogenous oxalate are its sole energy sources.
Calcium oxalate comprises the majority of kidney stones,
4
and
it has been hypothesized that the bacterium lowers the risk of
developing these stones by degrading oxalate in the colon and
hence reducing its excretion in the urine. In a recent study
conducted by our group, O. formigenes was associated with
a 70% reduction in the odds of a recurrence of calcium oxa-
late stones.
5
Overall, the incidence of renal stones in the
United States is about 2=1000
6–9
annually; *7% of American
women and 13% of American men, respectively, will experi-
ence a renal stone over the course of a lifetime.
10
Thus, the
public health implications of this relationship are potentially
large.
O. formigenes was first isolated and described in the 1980s by
Allison et al
3,11
Thus far, there has been little research focusing
on the natural history of this bacterium in human populations.
Although it appears that a large proportion of normal indi-
viduals are colonized, there is substantial variation in the re-
ported prevalence in adults. The estimate from our study was
*40% of healthy adult subjects from Massachusetts and North
Carolina
5
; findings from several small studies conducted in
various countries ranged from 46% to 77%.
12–21
Little is known
about when and how individuals become colonized or the
persistence of the bacterium over time. The only known factors
that reduce colonization are some antibiotics (there have been a
few reports in the literature,
22,23
but much of the information is
unpublished) and bile salts (based on animal studies
24
). There
are also limited clinical data suggesting that the prevalence
of O. formigenes is substantially reduced in various malab-
sorptive states and in cystic fibrosis,
11,14,21
which may be due
to excessive antibiotic use in the latter population. Here we
report findings from an evaluation of the determinants of
O. formigenes colonization based on an analysis of the control
subjects with no history of renal stones from our study in
Massachusetts and North Carolina.
1
Slone Epidemiology Center at Boston University, Boston, Massachusetts.
2
Channing Laboratory, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts.
3
University of Massachusetts Memorial Medical Center, Worcester, Massachusetts.
JOURNAL OF ENDOUROLOGY
Volume 25, Number 4, April 2011
ªMary Ann Liebert, Inc.
Pp. 673–679
DOI: 10.1089=end.2010.0462
673
Materials and Methods
The data were collected from 2004 to 2006, to address the
hypothesis that the presence of O. formigenes in the colon re-
duces predisposition to the formation of kidney stones; the
main findings have been published.
5
The study protocol was
approved by the Institutional Review Boards of the four in-
stitutions where patients were identified and by the Institu-
tional Review Board of the Boston University Medical
Campus. Written informed consent was obtained from all
participating subjects.
The original study included 247 patients aged 18–69 years
with recurrent episodes of calcium oxalate kidney stones. One
age, sex, and region-matched control was enrolled for each
case, selected from spouses, unrelated housemates, or friends
nominated by other cases or ineligible stone formers (e.g., with
another stone type); volunteer male controls were alsoenrolled.
A control nominated by a particular case was not matched to
that case. There were 259 initially enrolled controls.
Fecal swabs were collected by all subjects from stools
passed into paper collection devices placed in the subject’s
toilet. The swabs were then placed in Protocult tubes and
mailed in prepaid envelopes via an overnight courier. The
swabs were tested for O. formigenes using culture
3
and poly-
merase chain reaction (PCR).
25
The median elapsed time from
stool collection to culturing was 1 day, with a range of 0–6
days. Fewer than 1% of stool samples did not provide suffi-
cient material to culture. Specimens were cultured in selective
liquid oxalate–containing medium for 10 days. The medium
was then tested for the presence of oxalate by the addition of
calcium chloride. Although culture does not identify the or-
ganism directly, it demonstrates that oxalate is being de-
graded in the stool, and the culture medium is selective for
O. formigenes.
3
PCR, which can directly identify the bacterium,
proved to be insensitive as a primary test, but in a subset of
participants, it was conducted on the positive culture super-
natant: 96% were positive by PCR.
5
We therefore concluded
that the culture provided an adequate identification of
O. formigenes colonization.
Information was collected by telephone interview from all
subjects, including questions on known risk factors for kidney
stones, such as inflammatory bowel disease and family history
of stones, and on other relevant factors such as antibiotic use. A
lifetime history of use of antibiotics to which O. formigenes is
known to be sensitive (H. Sidhu, pers. comm.) was obtained.
As shown in Table 1, these included macrolides, tetracyclines,
chloramphenicol, rifampin, and metronidazole (henceforth
referred to as ‘sensitive’ antibiotics), which were asked about
by name. The use of other antibiotics (referred to as ‘‘non-
sensitive’ antibiotics) within the previous 5 years was also re-
corded; a lifetime history of use was not obtained.
Fluid intake and dietary history, including consumption of
oxalate-containing foods, were obtained by an adaptation of
the validated self-administered food frequency questionnaire
developed by the Nurses Health Study.
26
Total consumption
of oxalate and other dietary factors was estimated by linking
the questionnaire data with a database that contained
information on the contents of various nutrients in stan-
dardized portions of each food. Methodologic issues have
created controversy regarding the oxalate content of foods.
Recently, Holmes et al. have made progress in the reevalua-
tion and standardization of this nutrient,
27
and their
measurements were incorporated into the Nurses Health
Study database.
As noted, data from this study had previously demon-
strated an inverse relationship of O. formigenes with renal
stones.
5
That analysis also examined the effect of other factors
on the kidney stone=O. formigenes relation. The lack of re-
search on the natural history of this bacterium directed our
interest for further investigation to the identification of factors
associated with colonization with O. formigenes in a healthy
population, and for this reason the present analysis was
confined to the controls. Subjects were excluded if they had
taken any antibiotics within the three months before the in-
terview (n¼19) because of the likelihood that such very re-
cent use could result in an unrepresentatively low prevalence
of O. formigenes. This left 240 subjects; the median age was 49
years and 62% were men.
O. formigenes prevalence estimates were calculated within
strata of various factors. Odds ratios (OR) and 95% confidence
intervals (CIs) based on unconditional logistic regression
28
were used to assess potential confounding and to provide
statistical tests of apparent differences. In the logistic regres-
sion models, O. formigenes colonization (yes=no) was the de-
pendent variable; independent variables included factors that
were associated on a univariate basis, plus those not associ-
ated but of a priori interest. Factors included in the basic
model were age, sex, region, race=ethnicity, use of sensitive
antibiotics, use of any nonsensitive antibiotics, and quartiles
of the average daily intake of oxalate, calcium, vitamin C,
magnesium, and total calories. Trends in colonization ac-
cording to nutrient intake were tested by including ordinal
terms in the models, with values set to the medians of the
quartiles of consumption. Although crude ORs are given for
completeness, the multivariate estimates will generally be
referred to in describing the results.
Results
The prevalence of O. formigenes among the 240 subjects
was 38%. Table 2 displays the proportion colonized within
strata of demographic factors. There was no linear pattern
according to age; the lowest prevalence was 30% among
the youngest subjects, and the highest was 47% in subjects
aged 50–59 (OR, 2.5; 95% CI, 1.1–5.9). There were no
significant variations in colonization according to sex, race,
education, or region. In general, the multivariate ORs were
reasonably similar to the unadjusted estimates. The most
prominent exception was the OR for sex; in the compari-
son of women and men, the crude estimate was 1.2 and
the multivariate OR was 1.8. The inclusion of terms for use
of antibiotics in the model largely accounted for the dif-
ference in estimates.
Use of sensitive antibiotics was strongly related to coloni-
zation (Table 3): the prevalence estimates were 17%, 27%, and
36%, for those who had used these drugs <1 year ago, 1–5
years ago, and >5 years ago, respectively, compared with 55%
in nonusers. The ORs were significantly below 1.0 for sensi-
tive antibiotic use regardless of how recently this had oc-
curred. Compared with an estimate of 42% among nonusers,
the prevalence of colonization among those who had taken
nonsensitive antibiotics was 22% for last use <1 year ago and
39% for last use 1–5 years ago. The ORs were 0.3 and 0.8,
respectively, but the CIs included 1.0.
674 KELLY ET AL.
Subjects could have used both sensitive and nonsensitive
antibiotics during the 5-year exposure interval. To allow for
overlapping use, we examined the prevalence of O. formigenes
colonization according to five mutually exclusive categories
of sensitive and nonsensitive drug use (Table 4). Users within
the past 5 years were divided into three categories: sensitive
plus nonsensitive, sensitive only, and nonsensitive only.
Twenty-seven subjects had used both types, and only four of
these were O. formigenes positive (15%). The prevalence was
higher for subjects who used only sensitive antibiotics in the
last 5 years (27%), higher still for nonsensitive only users
(48%), and highest of all for those who had not taken any
antibiotics (59%). The ORs for the two categories that included
sensitive antibiotics were both significantly below 1.0, but not
statistically different from each other; the OR for the non-
sensitive only category was not significant. Users of sensitive
antibiotics >5 years ago were separated into those who had
also used nonsensitive antibiotics within the previous 5 years
and those who had not. The results for both categories were
nearly identical (prevalence estimates, 36%–38%; ORs, 0.3 for
each category), indicating minimal effect from the more recent
use of nonsensitive antibiotics. With one exception, the me-
dian interval since the most recent episode was higher in those
colonized with O. formigenes than in those who were not for
each of the five exposure categories; that is, the further in the
past that an antibiotic had been used, the greater the likeli-
hood of colonization.
With regard to the effects of specific antibiotics on
O. formigenes, sufficient numbers of users were available to
estimate the prevalence of colonization for two sensitive
Table 1. HC-1Oxalobacter formigenes Antibiotic Sensitivity Pattern
Antibiotic sensitivity Antibiotic resistance
Antibiotic
mg=mL
(or Units) Antibiotic
mg=mL
(or Units) Antibiotic
mg=mL
(or Units)
Chloramphenicol <1.5 Amikacin >18 Kanamycin >18
Colistin <0.5 Ampicillin >6 Lincomycin >1.2
Doxycycline <1.5 Amoxicillin >18 Nalidixic acid >18
Erythromycin 1.5 Bacitracin >6U Neomycin >18
Polymyxin B <15U Carbenicillin >60 Penicillin >6U
Rifampin 3 Cefaclor >18 Piperacillin >60
Tetracycline 3 Cefluroxime >18 Streptomycin 6
Ceftazidime >18 Sulfadiazine >150
Clindamycin >1.2 Tobramycin >6
Ciprofloxacin >3 Trimethoprim >3
Gentamycin >6 Vancomycin >18
Table 2. Prevalence of Oxalobacter formigenes
Among 240 Control Subjects
According to Demographic Factors
O. formigenes
positive
Factor No. (%)
Crude
OR
MVOR
(95% CI)
Age (years)
<40 17=56 (30) 1.0
a
1.0
a
40–49 26=72 (36) 1.3 1.5 (0.7–3.5)
50–59 33=70 (47) 2.1 2.5 (1.1–5.9)
60–69 18=42 (43) 1.7 1.8 (0.7–4.7)
Sex
Male 56=148 (38) 1.0
a
1.0
a
Female 38=92 (41) 1.2 1.8 (0.9–3.6)
Race
Non-Hispanic
white
75=198 (38) 1.0
a
1.0
a
Other 19=42 (45) 1.4 1.2 (0.6–2.8)
Education (year)
12 12=33 (36) 0.9 0.9 (0.3–2.3)
13–15 23=64 (36) 0.9 0.7 (0.3–1.5)
16 29=65 (45) 1.3 1.2 (0.6–2.6)
>16 30=78 (39) 1.0
a
1.0
a
Region
Massachusetts 71=179 (40) 1.0
a
1.0
a
North Carolina 23=61 (38) 0.9 0.8 (0.4–1.6)
a
Reference category.
CI ¼confidence interval; OR ¼odds ratio; MVOR ¼multivariate
odds ratio.
Table 3. Prevalence of Oxalobacter formigenes
Among 240 Control Subjects
According to Antibiotic Use
O. formigenes
positive
Antibiotic last use No. (%) Crude OR
MVOR
(95% CI)
Sensitive
a
None 51=92 (55) 1.0
b
1.0
b
<1 year 6=35 (17) 0.2 0.1 (0.05–0.4)
1–5 year 13=48 (27) 0.3 0.3 (0.1–0.6)
>5 year 24=65 (36) 0.5 0.4 (0.2–0.8)
Nonsensitive
c
None 67=161 (42) 1.0
b
1.0
b
<1 year 5=23 (22) 0.4 0.3 (0.1–1.0)
1–5 year 22=56 (39) 0.9 0.8 (0.4–1.6)
a
Erythromycin, clarithromycin, azithromycin, tetracycline, mino-
cycline, doxycycline, and metronidazole.
b
Reference category.
c
Ampicillin, amoxicillin, benzylpenicillin, dicloxacillin, penicillin
NOS, cephalexin, cefadroxil, cefaclor, cefprozil, clindamycin, vanco-
mycin, ciprofloxacin, levofloxacin, enrofloxacin, nitrofurantoin,
trimethoprim, sulfamethoxazole, sulfa NOS, and antiobiotic NOS.
COLONIZATION WITH OXALOBACTER FORMIGENES IN ADULTS 675
drugs, erythromycin and azithromycin, and one nonsensi-
tive drug, amoxicillin. The prevalence was 18% among 40
azithromycin users, 26% in 19 erythromycin users, and 29%
in 24 subjects who took other sensitive antibiotics. The ORs
were similar, ranging from 0.2 to 0.3, all with upper confi-
dence limits below 1.0. The prevalence among 21 amoxi-
cillin users was 38% (OR, 0.8), compared with 33% (OR, 0.6)
among 58 subjects who took other nonsensitive antibiotics.
An examination of selected nutrient factors is displayed in
Table 5. We obtained information on numerous nutrients, but
none were significantly associated with O. formigenes coloni-
zation, and many were highly correlated with each other. Here
we present results only for oxalate, a source of food for
O. formigenes, calcium and magnesium, which bind with oxa-
late, and vitamin C, which is metabolized to oxalate. The
prevalence of O. formigenes was lowest for the quartile of lowest
oxalate consumption and increased somewhat with increasing
intake (32%–45%). The ORs for the three quartiles of higher
consumption relative to the lowest reflected this linear pattern,
but none of the individual estimates was significantly elevated,
nor was there a statistically significant trend ( p¼0.14).
O. formigenes prevalence estimates did not differ according to
level of consumption for the remaining nutrients.
Among other factors, we also examined O. formigenes
prevalence according to body mass index, history of urinary
tract infection, family history of renal stones, and diuretic use.
There were no significant differences in colonization, with
ORs ranging from 1.0 to 1.2 (data not shown).
Discussion
Considerable evidence indicates that O. formigenes is the
primary organism that degrades oxalate in the colon.
29,30
Al-
though a few other species of intestinal bacteria, including
strains of Lactobacillus and Bifidobacterium, are also capable of
consuming oxalate and have recently been shown to carry the
same oxc and frc genes as O. formigenes.
31–37
these other bacteria
are generalists that consume other substrates as well as oxalate.
The present results suggest that the use of certain antibiotics
is the main factor affecting colonization with O. formigenes
among U.S. adults. Compared with nonusers, we observed a
markedly lower prevalence of colonization among individuals
who, in the last 5 years, had taken antibiotics to which the
bacterium has been reported to be sensitive, including macro-
lides, tetracyclines, chloramphenicol, rifampin, and metroni-
dazole. The reduction in colonization among users of these
drugs persisted after multivariate analysis, which adjusted for
several factors, including the use of nonsensitive antibiotics.
The prevalence was also reduced, but to a lesser extent, among
those who took these drugs >5 years ago. These findings
provide in vivo confirmation of unpublished in vitro sensitivity
testing (H. Sidhu, pers. comm.); there is only minimal pub-
lished information about the antibiotic sensitivity of the bac-
terium.
22,23
Among individual drugs, it was possible to
estimate the prevalence of colonization only for users of
erythromycin and azithromycin; both were clearly associated.
Results for use in the last 5 years of antibiotics that were
previously not thought to affect colonization were equivocal:
the prevalence estimates were somewhat lower than among
nonusers, particularly for recent use, but the ORs were not
significant. When mutually exclusive categories of the two
types of antibiotics were examined, the above findings were
largely confirmed. It is of interest that the use of sensitive
antibiotics >5 years ago had a more marked effect on preva-
lence than more recent use of nonsensitive antibiotics. While it
remains possible that O. formigenes might be sensitive to at
least some of the antibiotics that have not been previously
identified as affecting the bacterium, the only nonsensitive
antibiotic with a sufficient number of users to examine indi-
vidually was amoxicillin; the prevalence was actually higher
than that among users of other drugs in that category.
The results were consistent with some recolonization or
recovery to detectable levels of colonization after use of an-
tibiotics. For both sensitive and nonsensitive drugs, the
prevalence of O. formigenes was lowest when use was
comparatively recent. However, with the relatively small
numbers of users, the estimates were statistically compatible
with those for use in the more distant past. In the mutually
exclusive analysis, the median interval since last use was
generally higher for those who were positive for O. formigenes.
Table 4. Prevalence of Oxalobacter formigenes Among 240 Control Subjects
According to Mutually Exclusive Categories of Antibiotic Use
O. formigenes
Positive Negative
Antibiotic use No. (%) No. (%) Crude OR MVOR (95% CI)
None
a
36 (59) 25 (41) 1.0
b
1.0
b
Sensitiveþnonsensitive 5 year 4 (15) 23 (85) 0.1 0.1 (0.03–0.3)
Median interval since last use (month) 34 17
Sensitive only 5 year 15 (27) 41 (73) 0.3 0.2 (0.1–0.5)
Median interval since last use (month) 19 15
Nonsensitive only 5 year 15 (48) 16 (52) 0.7 0.6 (0.2–1.5)
Median interval since last use (month) 26 21
Sensitive >5 year only 16 (36) 28 (64) 0.5 0.3 (0.1–0.8)
Median interval since last use (month) 123 155
Sensitive >5 year þnonsensitive 5 year 8 (38) 13 (62) 0.5 0.3 (0.1–1.0)
Median interval since last use (month) 179 119
a
No use of sensitive antibiotics at any time, and no use of nonsensitive antibiotics in the previous 5 years.
b
Reference category.
676 KELLY ET AL.
With regard to other factors, there were no clear patterns in
the likelihood of being colonized with O. formigenes according
to age, sex, race, and education; there was also no evidence of
geographic variability. The only significant finding among the
demographic variables was a higher prevalence among sub-
jects in a middle age category (50–59 years), and with the
numerous subgroups evaluated, such a finding might be ex-
pected to occur by chance. Body mass index, history of uri-
nary tract infection, family history of renal stones, and use of
diuretics were not associated with colonization.
It is somewhat surprising that we did not observe a stronger
relation of colonization with oxalate consumption, since this
nutrient is one of two sources of energy for O. formigenes
(endogenous oxalate being the other). There was a modest in-
crease in prevalence with increasing consumption, but this was
not a significant trend. The equivocal results could be a re-
flection of imprecision in the measurement of dietary oxalate
muting a real effect. Among other dietary factors, the ORs for
quartiles of calcium, vitamin C, and magnesium consumption,
relative to the lowest levels, produced no clear differences.
A limitation to the evaluation of antibiotics was the lack of
information on use of nonsensitive drugs >5 years in the past. It
is also possible that antibiotic use was incompletely reported,
with the resulting misclassification of users as nonusers blur-
ring differences. This could particularly affect nonsensitive
drugs, which were not asked about by name. However, we
deem it unlikely that reporting of antibiotic was affected by
O. formigenesstatus, since this was not knownby study subjects.
Other potential limitations that should be considered are
information and selection bias. We judge that information bias
is unlikely for several reasons. Upon enrollment, study sub-
jects were unaware of the hypothesis and did not know
whether they were colonized with O. formigenes.Laboratory
testing of stool specimens was performed blind to case
control status and to all other factors.Other information was
obtained directly from the study subjects, by interview and
self-administered dietary questionnaire. The interview was
designed to maximize recall and was conducted by an
experienced nurse-interviewer; the self-completed dietary
questionnaire has been validated.
26,38,39
Selection bias is a the-
oretical possibility, given the participation rate of 76% among
control subjects; however, the decision to participate could not
have been related to O. formigenes status.
A caveat to the current analysis is that the original study
was not designed to explore patterns and determinants of
O. formigenes colonization, but rather to evaluate the relation
of the bacterium to the risk of recurrent calcium oxalate kidney
stones. The data collected from controls reported on here
provide a valuable opportunity to shed some light on factors
affecting the bacterium itself, about which little is known, but
there are limitations to using the study population for this
purpose. These include the incomplete information on anti-
biotic use that has already been discussed, geographic re-
striction to two regions of the United States, and confining the
study to adults. Specifically with regard to the latter restric-
tion, it was reported from a study of O. formigenes colonization
among Ukrainian children that the bacterium was not de-
tectable in neonates but was present in nearly all 6–9 year olds;
the prevalence then declined in adolescence.
25
This suggests
that O. formigenes may be acquired in infancy, a key aspect of
its natural history that we were not able to evaluate.
In conclusion, the present analysis has demonstrated that
colonization with O. formigenes is markedly affected by use of
antibiotics previously suspected to have an effect on the
bacterium. Questions remain concerning recolonization after
eradication and the effects of individual drugs. Although no
other factor was identified as having a material influence on
the prevalence of the bacterium, there is much to learn about
how an individual acquires the organism and which factors
affect persistence of colonization. As O. formigenes has no
known adverse effects and appears to have a greater capacity
to metabolize oxalate than other bacteria, there is potential for
its use as a probiotic to reduce the risk of commonly occurring
calcium oxalate renal stones.
Acknowledgments
We wish to thank Drs. Stephen P. Dretler, Glenn M. Pre-
minger, Richard K. Babayan, David Wang, Dianne Sacco, and
H. David Mitcheson for generously allowing us to enroll
kidney stone patients (who in turn nominated many of the
controls included in the present analysis) from their urological
practices; Erin Brockway, Robin Demasi, Barbara Mathias,
and Christine Tolis for their help with patient identification;
Dr. Ross Holmes for analysis of the oxalate content of foods
and general advice; and the study team at the Slone
Epidemiology Center: Lisa Crowell, Michael Bairos, Jean
McDonald, Gloria Uchegbu, and Peilan Lee.
This study was supported by grant R01 DK062270 from
the National Institute of Diabetes and Digestive and Kidney
Diseases.
Disclosure Statement
The authors have no conflicts of interest to declare.
Table 5. Prevalence of Oxalobacter formigenes
Among 240 Controls According to Dietary Factors
O. formigenes
positive
Nutrient mg=day No. (%)
Crude
OR
MVOR
(95% CI)
Oxalate
a
<115 19=60 (32) 1.0
b
1.0
b
115–169 23=60 (38) 1.3 1.3 (0.5–3.0)
170–239 25=60 (42) 1.5 1.6 (0.6–4.1)
240 27=60 (45) 1.8 2.1 (0.8–5.7)
Calcium
<550 23=58 (40) 1.0
b
1.0
b
550–819 25=63 (40) 1.0 0.7 (0.3–1.7)
820–1199 24=58 (41) 1.1 0.7 (0.2–1.7)
1200 22=61 (36) 0.9 0.6 (0.2–1.7)
Vitamin C
<75 23=61 (38) 1.0
b
1.0
b
75–139 23=61 (38) 1.0 0.7 (0.3–1.8)
140–244 24=59 (41) 1.1 1.0 (0.4–2.6)
245 24=59 (41) 1.1 0.8 (0.3–2.2)
Magnesium
<235 22=60 (37) 1.0
b
1.0
b
235–319 24=58 (41) 1.3 1.1 (0.4–3.2)
320–419 29=62 (47) 1.6 1.1 (0.3–3.8)
420 19=58 (33) 0.9 0.3 (0.1–1.4)
a
Test for trend, p¼0.14.
b
Reference category.
COLONIZATION WITH OXALOBACTER FORMIGENES IN ADULTS 677
References
1. Friedrich MJ. Microbiome project seeks to understand hu-
man body’s microscopic residents. JAMA 2008;300:777–778.
2. Mai V, Draganov PV. Recent advances and remaining gaps
in our knowledge of associations between gut microbiota
and human health. World J Gastroenterol 2009;15:81–85.
3. Allison MJ, Dawson KA, Mayberry WR, Foss JG. Oxalobacter
formigenes gen. nov., sp. nov.: Oxalate-degrading anaerobes that
inhabit the gastrointestinal tract. Arch Microbiol 1985;141:1–7.
4. Coe F, Parks J, eds. Nephrolithiasis: Pathogenesis and
Treatment. Chicago: Year Book Medical, 1988.
5. Kaufman DW, Kelly JP, Curhan GC, et al. Oxalobacter for-
migenes may reduce the risk of calcium oxalate kidney
stones. J Am Soc Nephrol 2008;19:1197–1203.
6. Hiatt RA, Dales LG, Friedman GD, Hunkeler EM. Frequency
of urolithiasis in a prepaid medical care program. Am J
Epidemiol 1982;115:255–265.
7. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A pro-
spective study of dietary calcium and other nutrients and the
risk of symptomatic kidney stones. N Engl J Med 1993;328:
833–838.
8. Curhan GC, Willett WC, Speizer FE, et al.Comparison of
dietary calcium with supplemental calcium and other
nutrients as factors affecting the risk for kidney stones in
women. Ann Intern Med 1997;126:497–504.
9. Curhan GC, Willett WC, Knight EL, Stampfer MJ. Dietary fac-
tors and the risk of incident kidney stones in younger women:
Nurses’ Health Study II. Arch Intern Med 2004;164:885–891.
10. Stamatelou KK, Francis ME, Jones CA, et al.Time trends in
reported prevalence of kidney stones in the United States:
1976–1994. Kidney Int 2003;63:1817–1823.
11. Allison MJ, Cook HM, Milne DB, et al.Oxalate degradation by
gastrointestinal bacteria from humans. J Nutr 1986;116:455–460.
12. Kleinschmidt K, Mahlmann A, Hautmann R. Oxalate de-
grading bacteria in the gut—do they influence calcium ox-
alate stone formation? In: Ryall R, Bais R, Marshall VR, eds.
Urolithiasis 2. New York: Plenum Press, 1994, pp. 439–441.
13. Han JZ, Zhang X, Li JG, Zhang YS. The relationship of Ox-
alobacter formigenes and calcium oxalate calculi. J Tongji Med
Univ 1995;15:249–252.
14. Sidhu H, Hoppe B, Hesse A, et al.Absence of Oxalobacter
formigenes in cystic fibrosis patients: A risk factor for hy-
peroxaluria. Lancet 1998;352:1026–1029.
15. Sidhu H, Schmidt ME, Cornelius JG, et al.Direct correlation
between hyperoxaluria=oxalate stone disease and the absence
of the gastrointestinal tract-dwelling bacterium Oxalobacter
formigenes: Possible prevention by gut recolonization or en-
zyme replacement therapy. J Am Soc Nephrol 1999;10 Suppl
14:S334–S340.
16. Neuhaus TJ, Belzer T, Blau N, et al.Urinary oxalate excretion
in urolithiasis and nephrocalcinosis. Arch Dis Child 2000;
82:322–326.
17. Schmidt ME, Muller SC, Hesse A, et al.Signification of the
bacterium Oxalobacter formigenes in case of development of
calcium oxalate urolithiasis after antibiotic treatment. J Urol
2001;165:S246.
18. Kwak C, Jeong BC, Lee JH, et al.Molecular identification of
Oxalobacter formigenes with the polymerase chain reaction in
fresh or frozen fecal samples. BJU Int 2001;88:627–632.
19. Kumar R, Mukherjee M, Bhandari M, et al.Role of
Oxalobacter formigenes in calcium oxalate stone disease: A
study from North India. Eur Urol 2002;41:318–322.
20. Troxel SA, Sidhu H, Kaul P, Low RK. Intestinal Oxalobacter
formigenes colonization in calcium oxalate stone formers
and its relation to urinary oxalate. J Endourol 2003;17:173–176.
21. Kumar R, Ghoshal UC, Singh G, Mittal RD. Infrequency of
colonization with Oxalobacter formigenes in inflammatory
bowel disease: Possible role in renal stone formation.
J Gastroenterol Hepatol 2004;19:1403–1409.
22. Duncan SH, Richardson AJ, Kaul P, et al. Oxalobacter
formigenes and its potential role in human health. Appl En-
viron Microbiol 2002;68:3841–3847.
23. Mittal RD, Kumar R, Bid HK, Mittal B. Effect of antibiotics
on Oxalobacter formigenes colonization of human gastroin-
testinal tract. J Endourol 2005;19:102–106.
24. Argenzio RA, Liacos JA, Allison MJ. Intestinal oxalate-
degrading bacteria reduce oxalate absorption and toxicity in
guinea pigs. J Nutr 1988;118:787–792.
25. Sidhu H, Enatska L, Ogden S, et al.Evaluating children in
the Ukraine for colonization with the intestinal bacterium
Oxalobacter formigenes, using a polymerase chain reaction-
based detection system. Mol Diagn 1997;2:89–97.
26. Willett WC, Sampson L, Stampfer MJ, et al.Reproducibility
and validity of a semiquantitative food frequency ques-
tionnaire. Am J Epidemiol 1985;122:51–65.
27. Holmes RP, Kennedy M. Estimation of the oxalate content of
foods and daily oxalate intake. Kidney International 2000;57:
1662–1667.
28. Schlesselman JJ. Case-Control Studies: Design, Conduct,
Analysis. New York: Oxford University Press, 1982.
29. Allison MJ, Daniel SL, Cornick NA. Oxalate-degrading
bacteria. In: Kahn SR, ed. Calcium Oxalate in Biological
Systems. New York: CRC Press, 1995, pp. 131–168.
30. Stewart CS, Duncan SH, Cave DR. Oxalobacter formigenes
and its role in oxalate metabolism in the human gut. FEMS
Microbiol Lett 2004;230:1–7.
31. Campieri C, Campieri M, Bertuzzi V, et al.Reduction of
oxaluria after an oral course of lactic acid bacteria at high
concentration. Kidney Int 2001;60:1097–1105.
32. Federici F, Vitali B, Gotti R, et al.Characterization and het-
erologous expression of the oxalyl coenzyme A decarbox-
ylase gene from Bifidobacterium lactis. Appl Environ
Microbiol 2004;70:5066–5073.
33. Goldfarb DS. Microorganisms and calcium oxalate stone
disease. Nephron Physiol 2004;98:p48–p54.
34. Lieske JC, Goldfarb DS, De Simone C, Regnier C. Use of a
probiotic to decrease enteric hyperoxaluria. Kidney Int
2005;68:1244–1249.
35. Kwak C, Jeong BC, Ku JH, et al.Prevention of ne-
phrolithiasis by Lactobacillus in stone-forming rats: A pre-
liminary study. Urol Res 2006;34:265–270.
36. Turroni S, Vitali B, Bendazzoli C, et al.Oxalate consumption
by lactobacilli: Evaluation of oxalyl-CoA decarboxylase and
678 KELLY ET AL.
formyl-CoA transferase activity in Lactobacillus acidophilus.
J Appl Microbiol 2007;103:1600–1609.
37. Lewanika TR, Reid SJ, Abratt VR, et al.Lactobacillus gasseri
Gasser AM63(T) degrades oxalate in a multistage continu-
ous culture simulator of the human colonic microbiota.
FEMS Microbiol Ecol 2007;61:110–120.
38. Rimm EB, Giovannucci EL, Stampfer MJ, et al.Reproduci-
bility and validity of an expanded self-administered semi-
quantitative food frequency questionnaire among male
health professionals. Am J Epidemiol 1992;135:1114–1126;
discussion 27–36.
39. Willett WC. Nutritional Epidemiology, 2nd editon. New
York: Oxford University Press, 1998.
Address correspondence to:
Judith Parsells Kelly, M.S.
Slone Epidemiology Center
at Boston University
1010 Commonwealth Avenue
Boston, MA 02215
E-mail: jlpkelly@bu.edu
Abbreviations Used
CI ¼confidence interval
OR ¼odds ratio
PCR ¼polymerase chain reaction
COLONIZATION WITH OXALOBACTER FORMIGENES IN ADULTS 679
... This temporary variation in a composition can cause urological infectious disease, and it has a chance to get recovered by probiotic intake such as Lactobacillus spp. (Kelly et al. 2011;Cho and Blaser 2012). In a life cycle, aging process is a cause of diversification of diversity and composition changes will alter with number and type of genera (Kelly et al. 2011). ...
... (Kelly et al. 2011;Cho and Blaser 2012). In a life cycle, aging process is a cause of diversification of diversity and composition changes will alter with number and type of genera (Kelly et al. 2011). ...
Chapter
Microorganisms often coexist with each other in close proximity such as micro-colonies or biofilms and are rare to be obtained as pure cultures from the environment. Hence, there is always a likelihood of microbe–microbe interactions among these communities, which can either be positive or negative. Various factors such as physical, chemical, biological and genetics regulate such interactions and the molecular mechanisms involved in these interactions between microorganisms. One of the most important positive microbial interactions is synergism. Microbial synergism is defined as the microbial interaction in which both or all the microbial population involved gets benefitted, by supporting each other’s growth and proliferation. These cooperative systems are ubiquitous in nature and are involved in various beneficial activities such as driving various biogeochemical processes, enhancing soil biomass and nutrients, promoting plant growth, degradation of food in the colon, waste water treatment, medicine and food industry. Therefore, in the present chapter we explore the different types of microbial interactions and cooperation between communities. Further, we also discuss the chemical basis of synergism and the factors which influences the synergistic process such as environment, substrate, etc. Finally, this chapter emphasizes the potential applications and future prospects of microbial synergism in the field of medicine, food, agriculture and environment.
... This temporary variation in a composition can cause urological infectious disease, and it has a chance to get recovered by probiotic intake such as Lactobacillus spp. (Kelly et al. 2011;Cho and Blaser 2012). In a life cycle, aging process is a cause of diversification of diversity and composition changes will alter with number and type of genera (Kelly et al. 2011). ...
... (Kelly et al. 2011;Cho and Blaser 2012). In a life cycle, aging process is a cause of diversification of diversity and composition changes will alter with number and type of genera (Kelly et al. 2011). ...
Book
Full-text available
The book overviews the complex interactions amongst the microbes and their possible applications. Emphasis has been made to include a wide spectrum of experimental and theoretical contributions from eminent researchers in the field. Microbial communities are the assemblages of microorganisms of various species which live together in the same environment and continuously interact with each other. The microbial cells in communities display unique phenotypes that affect the survival and reproduction of other cells present around them. These phenotypes constitute the social adaptations that drive the interactions between microbial cells. The interactions, further determine the productivity, stability and the ability of community to resist the environmental perturbations. These microbial communities live with extremely competitive niche and fight for their survival and genetic persistence. But they frequently appear in niche with multifaceted and interactive webs rather than the planktonic nature. This can be within the same species or with different species, or even with diverse genera and families. It either a competitive winner community whereas the “weaker” strain goes extinct or a competitor that coexist with their metabolic secretory potentials or a separator that assigned their own community territorial niches. Sometimes, it can be neutral or tritagonist. These microbial associations within the microbiome provides the foundation for diverse forms of microbial ecology and determined the applied perspectives for agriculture, clinical and industrial sectors. This book will be useful to postgraduate students, researchers from academic as well as industry working in the field of microbial exploration with keen interest in survival factors and mechanism of their survival by various ecological and functional strategies.
... In healthy Japanese participants, 80% of 54 male and 62% of 34 female subjects showed colonization with O. formigenes (45). In two large cohort studies of healthy American adults, ;30% were colonized with O. formigenes (46,47). This is considerably lower than other countries. ...
... Two large cohort studies with humans have investigated O. formigenes-host relationships. Kelly and colleagues' analysis of 94 O. formigenes-colonized subjects and 146 noncolonized healthy individuals did not show any impact of sex, race, education, region of U.S. residence, body mass index, history of urinary tract infection, family history of renal stones, and diuretic use on frequency of O. formigenes colonization (47). In a multivariate analysis of more than 4,900 samples in the AGP database, the relative abundance of O. formigenes was associated with increased age, female sex, Caucasian ethnicity, non-USA residence, normal BMI, higher educational attainment, and absence of antibiotics exposure within a year (51). ...
Article
Oxalobacter formigenes, a unique anaerobic bacterium that relies solely on oxalate for growth, is a key oxalate-degrading bacterium in the mammalian intestinal tract. Degradation of oxalate in the gut by O. formigenes plays a critical role in preventing renal toxicity in animals that feed on oxalate-rich plants. The role of O. formigenes in reducing the risk of calcium oxalate kidney stone disease and oxalate nephropathy in humans is less clear, in part due to difficulties in culturing this organism, and the lack of studies which have utilized diets controlled in their content of oxalate. Herein, we review the literature on the 40th anniversary of the discovery of O. formigenes, with a focus on its biology, its role in gut oxalate metabolism and calcium oxalate kidney stone disease, and potential areas of future research. Results from ongoing clinical trials utilizing O. formigenes in healthy volunteers and in patients with Primary Hyperoxaluria Type 1 (PH1), a rare but severe form of calcium oxalate kidney stone disease, will also be discussed. Information has been consolidated on O. formigenes strains and best practices to culture this bacterium, which should serve as a good resource for researchers.
... Human gut microflora has emerged as a key contributor to oxalate nephrolithiasis. The Gram-negative anaerobic bacterium Oxalobacter formigenes utilizes oxalate as a primary energy source and has been found to colonize the gastrointestinal tract in a third of individuals [17]. Case-control studies have suggested that colonization with O. formigenes can reduce individual risk of recurrent oxalate stone formation by up to 70% [18]. ...
Article
Full-text available
Short gut syndrome can lead to type 3 intestinal failure, and nutrition and hydration can only be achieved with parenteral nutrition (PN). While this is a lifesaving intervention, it carries short- and long-term complications leading to complex comorbidities, including chronic kidney disease. Through a patient with devastating inflammatory bowel disease’s journey, this review article illustrates the effect of short gut and PN on kidney function, focusing on secondary hyperoxaluria and acute precipitants of glomerular filtration. In extensive small bowel resections colon in continuity promotes fluid reabsorption and hydration but predisposes to hyperoxaluria and stone disease through the impaired gut permeability and fat absorption. It is fundamental, therefore, for dietary intervention to maintain nutrition and prevent clinical deterioration (i.e., sarcopenia) but also to limit the progression of renal stone disease. Adaptation of both enteral and parenteral nutrition needs to be individualised, keeping in consideration not only patient comorbidities (short gut and jejunostomy, cirrhosis secondary to PN) but also patients’ wishes and lifestyle. A balanced multidisciplinary team (renal physician, gastroenterologist, dietician, clinical biochemist, pharmacist, etc.) plays a core role in managing complex patients, such as the one described in this review, to improve care and overall outcomes.
... Therefore, in almost all studies with O. formigenes, conventional PCR was used to identify gastrointestinal bacteria (24)(25)(26), but in one study, a realtime PCR was used to count the number of O. formigenes in a healthy group (5 is not yet clear. However, the use of antibiotics is thought to be a factor in colonization (28,29). In the study of Batislam et al. for the first time, a qPCR method based on the OXC gene was used to identify the exact extent of colonization in patients with kidney stones. ...
Article
Full-text available
Background: Urinary stones are a major problem world, and their incidence has increased significantly in recent years. Objectives: This study aimed to develop a simple and rapid molecular method based on PCR and qPCR assays to detect Oxalobacter formigenes (which causes oxalate degradation in intestines) in fecal samples of healthy volunteers and patients with calcium oxalate nephrolithiasis, and determine the amount of urinary oxalate in the two groups. Methods: This study was performed on urine and fecal samples of 73 patients with kidney stones and 52 healthy individuals. After DNA extraction, PCR and qPCR assays were performed on two gene regions of Oxalobacter formigenes, OXC, and FRC. Also, urine oxalate was measured in the study population using biochemical methods. Results: We found that the presence of Oxalobacter formigenes could reduce the risk of kidney stones and calcium oxalate stones. In fact, both FRC and OXC genes were involved in the diagnosis of Oxalobacter formigenes; however, the results based on the FRC gene showed higher efficiency. In addition, the presence or absence of stones did not affect the amount of urinary excretion of oxalate, rather it is affected by diet. Conclusions: Molecular identification of Oxalobacter formigenes by PCR and qPCR assays allows rapid, specific, and reproducible detection in fecal samples, which also allows immediate processing of these samples in clinical conditions.
... Since there is no consensus on the best method to detect O. formigenes in stool samples, we developed a positivity score based on PCR, qPCR and 16S rRNA gene sequencing data at multiple time points to accurately represent O. formigenes positivity in the stool samples of the study subjects. Based on the O. formigenes positivity score, the prevalence of O. formigenes was 50% in the 64 participants at baseline (Figs. 1, 2), similar to prior findings in the USA 20,22,24,27 . The O. formigenespositive and negative participants were similar in distributions of age, sex, ethnicity, BMI, mode of birth-delivery, H. pylori status, and place of birth (Table S2). ...
Article
Full-text available
The incidence of kidney stones is increasing in the US population. Oxalate, a major factor for stone formation, is degraded by gut bacteria reducing its intestinal absorption. Intestinal O. formigenes colonization has been associated with a lower risk for recurrent kidney stones in humans. In the current study, we used a clinical trial of the eradication of Helicobacter pylori to assess the effects of an antibiotic course on O. formigenes colonization, urine electrolytes, and the composition of the intestinal microbiome. Of 69 healthy adult subjects recruited, 19 received antibiotics for H. pylori eradication, while 46 were followed as controls. Serial fecal samples were examined for O. formigenes presence and microbiota characteristics. Urine, collected serially fasting and following a standard meal, was tested for oxalate and electrolyte concentrations. O. formigenes prevalence was 50%. Colonization was significantly and persistently suppressed in antibiotic-exposed subjects but remained stable in controls. Urinary pH increased after antibiotics, but urinary oxalate did not differ between the control and treatment groups. In subjects not on antibiotics, the O. formigenes-positive samples had higher alpha-diversity and significantly differed in Beta-diversity from the O. formigenes-negative samples. Specific taxa varied in abundance in relation to urinary oxalate levels. These studies identified significant antibiotic effects on O. formigenes colonization and urinary electrolytes and showed that overall microbiome structure differed in subjects according to O. formigenes presence. Identifying a consortium of bacterial taxa associated with urinary oxalate may provide clues for the primary prevention of kidney stones in healthy adults.
Article
Urolithiasis, referred to as the formation of stones in the urinary tract, is a common disease with growing prevalence and high recurrence rate worldwide. Although researchers have endeavoured to explore the mechanism of urinary stone formation for novel effective therapeutic and preventative measures, the exact aetiology and pathogenesis remain unclear. Propelled by sequencing technologies and culturomics, great advances have been made in understanding the pivotal contribution of the human microbiome to urolithiasis. Indeed, there are diverse and abundant microbes interacting with the host in the urinary tract, overturning the dogma that urinary system, and urine are sterile. The urinary microbiome of stone formers was clearly distinct from healthy individuals. Besides, dysbiosis of the intestinal microbiome appears to be involved in stone formation through the gut-kidney axis. Thus, the human microbiome has potential significant implications for the aetiology of urolithiasis, providing a novel insight into diagnostic, therapeutic, and prognostic strategies. Herein, we review and summarize the landmark microbiome studies in urolithiasis and identify therapeutic implications, challenges, and future perspectives in this rapidly evolving field. To conclude, a new front has opened with the evidence for a microbial role in stone formation, offering potential applications in the prevention, and treatment of urolithiasis.
Chapter
Urinary system has its own micro-environmental niche, and microbes with their genes and metabolic products are the components of the constitutes; hence, we referred them as urinary microbiome. Microbial residents of urinary system comprise the diversified types of microbes, their genes, genome, and metabolites and have the greatest impact on the urinary system performance. Unlike others, urinary lithiasis or stone formation in urinary system is the commonest reason to healthcare system burden. Such urolithiasis phenomena considered to be a part of lifestyle disorder is well perceived now. Whereas, prevalence in general population recorded as 10% and most of the times 20% reported from stone belt areas. Urinary stones are with different types of chemical nature, mostly derived from the metabolic product saturation inside the excretory systems. We are able to understand that the metabolic origin products in urinary system have the impact to derivatize the lithiasis activity, mostly along with supersaturation in solutes and by means of the micro-environment changes pertaining to the urinary niche.
Chapter
Epithelial oxalate transport is fundamental to the role occupied by the gastrointestinal (GI) tract in oxalate homeostasis. The absorption of dietary oxalate, together with its secretion into the intestine, and degradation by the gut microbiota, can all influence the excretion of this nonfunctional terminal metabolite in the urine. Knowledge of the transport mechanisms is relevant to understanding the pathophysiology of hyperoxaluria, a risk factor in kidney stone formation, for which the intestine also offers a potential means of treatment. The following discussion presents an expansive review of intestinal oxalate transport. We begin with an overview of the fate of oxalate, focusing on the sources, rates, and locations of absorption and secretion along the GI tract. We then consider the mechanisms and pathways of transport across the epithelial barrier, discussing the transcellular, and paracellular components. There is an emphasis on the membrane-bound anion transporters, in particular, those belonging to the large multifunctional Slc26 gene family, many of which are expressed throughout the GI tract, and we summarize what is currently known about their participation in oxalate transport. In the final section, we examine the physiological stimuli proposed to be involved in regulating some of these pathways, encompassing intestinal adaptations in response to chronic kidney disease, metabolic acid-base disorders, obesity, and following gastric bypass surgery. There is also an update on research into the probiotic, Oxalobacter formigenes, and the basis of its unique interaction with the gut epithelium. © 2021 American Physiological Society. Compr Physiol 11:1-41, 2021.
Chapter
Kidney stones are becoming more common and are associated with significant morbidity. In the current day, it is well understood that nutritional factors play a role in the development of kidney stones. Putative dietary promoters of calcium-containing stones include high sodium, high protein, and high sucrose intake. Putative dietary inhibitors of calcium-containing stones include higher potassium, high magnesium, high fiber, and high vitamin B6 intake. The American Urologic Association, the European Association of Urology, and other organizations have recently published dietary guidelines (generally expert opinion) for the management of kidney stones. We will review the data for optimal fluid, calcium, protein, sodium, citrate, vitamin C, vitamin D, sugar, potassium, and phytate intake. New insights into the physiology of stone formation may illuminate the similarity of disease progression to vascular calcification and inflammation, which gives rise to coronary artery disease (CAD). The implications may be that a diet intended to prevent kidney stones may mitigate diabetes, metabolic syndrome, and high blood pressure while addressing the risk for CAD and low bone mineral density. For that reason, we also promote the US Dietary Guidelines for Americans 2015–20, which promote health in general. Although those guidelines do not specifically address kidney stones and have not been tested for that purpose, we believe that adherence to those guidelines would likely reduce stones, promote bone health, and reduce metabolic syndrome and its accompanying comorbidities (https://health.gov/dietaryguidelines/2015/guidelines/).
Article
Full-text available
The authors assessed the reproducibility and validity of an expanded 131-item semiquantitative food frequency questionnaire used in a prospective study among 51,529 men. The form was administered by mail twice to a sample of 127 participants at a one-year interval. During this interval, men completed two one-week diet records spaced approximately 6 months apart. Mean values for intake of most nutrients assessed by the two methods were similar. Intraclass correlation coefficients for nutrient intakes assessed by questionnaires one year apart ranged from 0.47 for vitamin E without supplements to 0.80 for vitamin C with supplements. Correlation coefficients between the energy-adjusted nutrient intakes measured by diet records and the second questionnaire (which asked about diet during the year encompassing the diet records) ranged from 0.28 for iron without supplements to 0.86 for vitamin C with supplements (mean r = 0.59). These correlations were higher after adjusting for week-to-week variation in diet record intakes (mean r = 0.65). These data indicate that the expanded semiquantitative food frequency questionnaire is reproducible and provides a useful measure of intake for many nutrients over a one-year period.
Chapter
Several hundred milligrams of dietary oxalate pass daily through the human gastrointestinal tract. Nutrition therefore represents the largest potential source of oxalate for the human body. Hodgkinson estimated that approximately half the ingested oxalate is destroyed by bacterial action. Oxalate is absorbed via the intestinal mucosa by an ion exchange process. Two to 20% of the ingested oxalate in absorbed via the ileal or colonic mucosa. The rest is considered thus far to be excreted in the feces5, 6.
Article
The intestinal Oxalobacter Formigenes were isolated in 30 cases of urolithiasis and in 45 controls. The biologic characters and morphology of the bacteria were also observed. The results showed that the colony counts in urolith group 9 (mean l03/g. faeces) were significantly less than that of controls (mean l08g. faeces) (P<0. 001). It is believed that the lesser amount of oxalobacter formigenes in urolith was the important factor of the calcium oxalate calculi formation.
Article
Background:Oxalobacter formigenes is a recently discovered anaerobic bacterium residing in the gastrointestinal tracts of most vertebrates, including humans. Evidence suggests that this bacterium plays an important symbiotic relationship with its hosts by regulating oxalic acid homeostasis. Oxalic acid is a ubiquitous toxic by-product of metabolism associated with numerous pathologic conditions, including hyperoxaluria, cardiac myopathy and conductance disorders, kidney stones, and even death. Despite the potential importance of O. formigenes in several major health disorders, the difficulty in culturing, isolating, and identifying this fastidious anaerobe has limited research of its disease associations. Because O. formigenes must use two unique enzymes to catabolize oxalic acid, this bacterium appeared to be a suitable model for DNA-based identification, thereby circumventing the labor-intensive procedures currently used.Methods and Results:In this study, genus- and group-specific oligonucleotide sequences were designed corresponding to homologous regions residing in the oxc gene that enodes for oxalyl-coenzyme A decarboxylase. A polymerase chain reaction (PCR)-based amplification of the 5′ end of this gene directly from genomic DNA isolated from various strains of O. formigenes was used to show that the genus- and group-specific oligonucleotide probes could identify and subgroup the bacterium. Field testing of this PCR-based detection system with 100 fecal cultures collected from children aged 0–12 years demonstrated the ease and efficacy with which O. formigenes can now be identified. Furthermore, these latter data provide a profile for the natural colonization of a human population with this intestinal bacterium.Conclusions:Development and use of this PCR-based detection system permit the rapid identification and classification of the gut-associated bacterium O. formigenes, thereby circumventing the need for the more labor-intensive and lengthy method currently used. The first field test of this detection system indicates that humans apparently do not become colonized with O. formigenes until they begin crawling about in the environment. Furthermore, studies investigating the association between several disorders (eg, kidney stones, irritable bowel syndrome, and hyperoxaluria) and the absence of the bacterium from the gut will now prove far easier.
Article
The complex gut microbial flora harbored by individuals (microbiota) has long been proposed to contribute to intestinal health as well as disease. Pre- and probiotic products aimed at improving health by modifying microbiota composition have already become widely available and acceptance of these products appears to be on the rise. However, although required for the development of effective microbiota based interventions, our basic understanding of microbiota variation on a population level and its dynamics within individuals is still rudimentary. Powerful new parallel sequence technologies combined with other efficient molecular microbiota analysis methods now allow for comprehensive analysis of microbiota composition in large human populations. Recent findings in the field strongly suggest that microbiota contributes to the development of obesity, atopic diseases, inflammatory bowel diseases and intestinal cancers. Through the ongoing National Institutes of Health Roadmap 'Human Microbiome Project' and similar projects in other parts of the world, a large coordinated effort is currently underway to study how microbiota can impact human health. Translating findings from these studies into effective interventions that can improve health, possibly personalized based on an individuals existing microbiota, will be the task for the next decade(s).
Article
Boston—The human body is one of the richest habitats on Earth, with trillions of microorganisms inhabiting this mobile biome. Yet only a few dozen of the most notorious of these microbes are well known, their pathogenic exploits having outshadowed those of other microorganisms that coexist harmoniously with their human hosts.The majority of commensal microorganisms that inhabit the gut, skin, oral cavity, and other niches within the human body may be veritable strangers, but they are becoming more familiar as researchers begin to explore the microbial ecosystems that constitute the collective realm called the human “microbiome.” To better understand the structure and function of these microbial communities and the roles they play in health and disease, the National Institutes of Health launched the Human Microbiome Project in December 2007.