Factors Related to Colonization
with Oxalobacter formigenes in U.S. Adults
Judith Parsells Kelly, M.S.,
Gary C. Curhan, M.D., Sc.D.,
David R. Cave, M.D., Ph.D.,
Theresa E. Anderson, R.N.,
and David W. Kaufman, Sc.D.
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.
In recent years there has been increasing interest in ex-
ploring the probiotic potential of intestinal microbiota.
promising example is Oxalobacter formigenes, a gram-negative,
obligately anaerobic bacterium that inhabits the mamma-
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,
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-
Overall, the incidence of renal stones in the
United States is about 2=1000
annually; *7% of American
women and 13% of American men, respectively, will experi-
ence a renal stone over the course of a lifetime.
public health implications of this relationship are potentially
O. formigenes was ﬁrst isolated and described in the 1980s by
Allison et al
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
; ﬁndings from several small studies conducted in
various countries ranged from 46% to 77%.
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,
but much of the information is
unpublished) and bile salts (based on animal studies
are also limited clinical data suggesting that the prevalence
of O. formigenes is substantially reduced in various malab-
sorptive states and in cystic ﬁbrosis,
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.
Slone Epidemiology Center at Boston University, Boston, Massachusetts.
Channing Laboratory, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts.
University of Massachusetts Memorial Medical Center, Worcester, Massachusetts.
JOURNAL OF ENDOUROLOGY
Volume 25, Number 4, April 2011
ªMary Ann Liebert, Inc.
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.
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
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
merase chain reaction (PCR).
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
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.
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.
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,
measurements were incorporated into the Nurses Health
As noted, data from this study had previously demon-
strated an inverse relationship of O. formigenes with renal
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
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.
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
(or Units) Antibiotic
(or Units) Antibiotic
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
Factor No. (%)
<40 17=56 (30) 1.0
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)
Male 56=148 (38) 1.0
Female 38=92 (41) 1.2 1.8 (0.9–3.6)
75=198 (38) 1.0
Other 19=42 (45) 1.4 1.2 (0.6–2.8)
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
Massachusetts 71=179 (40) 1.0
North Carolina 23=61 (38) 0.9 0.8 (0.4–1.6)
CI ¼conﬁdence interval; OR ¼odds ratio; MVOR ¼multivariate
Table 3. Prevalence of Oxalobacter formigenes
Among 240 Control Subjects
According to Antibiotic Use
Antibiotic last use No. (%) Crude OR
None 51=92 (55) 1.0
<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)
None 67=161 (42) 1.0
<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)
Erythromycin, clarithromycin, azithromycin, tetracycline, mino-
cycline, doxycycline, and metronidazole.
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).
Considerable evidence indicates that O. formigenes is the
primary organism that degrades oxalate in the colon.
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.
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-
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
Antibiotic use No. (%) No. (%) Crude OR MVOR (95% CI)
36 (59) 25 (41) 1.0
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
No use of sensitive antibiotics at any time, and no use of nonsensitive antibiotics in the previous 5 years.
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.
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.
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.
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
The authors have no conﬂicts of interest to declare.
Table 5. Prevalence of Oxalobacter formigenes
Among 240 Controls According to Dietary Factors
Nutrient mg=day No. (%)
<115 19=60 (32) 1.0
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)
<550 23=58 (40) 1.0
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)
<75 23=61 (38) 1.0
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)
<235 22=60 (37) 1.0
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)
Test for trend, p¼0.14.
COLONIZATION WITH OXALOBACTER FORMIGENES IN ADULTS 677
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
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:
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
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
16. Neuhaus TJ, Belzer T, Blau N, et al.Urinary oxalate excretion
in urolithiasis and nephrocalcinosis. Arch Dis Child 2000;
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
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:
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
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
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;
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
CI ¼conﬁdence interval
OR ¼odds ratio
PCR ¼polymerase chain reaction
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