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

Abstract

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.

Full text

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

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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