161. J Clin Gastroenterol. 2014 Nov-Dec;48 Suppl 1:S28-31. doi:
Gut microbiota, host gene expression, and aging.
Patrignani P(1), Tacconelli S, Bruno A.
(1)Department of Neuroscience and Imaging, Section of Cardiovascular and
Pharmacological Sciences, Center of Excellence on Aging (CeSI), "G. d'Annunzio"
University, Chieti, Italy.
Novel concepts of disease susceptibility and development suggest an important
role of gastrointestinal microbiota and microbial pathogens. They can contribute
to physiological systems and disease processes, even outside of the
gastrointestinal tract. There is increasing evidence that genetics of the host
influence and interact with gut microbiota. Moreover, aging-associated oxidative
stress may cause morphologic alterations of bacterial cells, thus influencing the
aggressive potential and virulence markers of an anaerobic bacterium and finally
the type of interaction with the host. At the same time, microbiota may influence
host gene expression and it is becoming apparent that it may occur through the
regulation of microRNAs. They are short single-stranded noncoding RNAs that
regulate posttranscriptional gene expression by affecting mRNA stability and/or
translational repression of their target mRNAs. The introduction of -omics
approaches (such as metagenomics, metaproteomics, and metatranscriptomics) in
microbiota research will certainly advance our knowledge of this area. This will
lead to greatly deepen our understanding of the molecular targets in the
homeostatic interaction between the gut microbiota and the host and, thereby,
promises to reveal new ways to treat diseases and maintain health.
PMID: 25291121 [PubMed - indexed for MEDLINE]
162. Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820. Epub 2013 Dec 11.
Diet rapidly and reproducibly alters the human gut microbiome.
David LA(1), Maurice CF(2), Carmody RN(2), Gootenberg DB(2), Button JE(2), Wolfe
BE(2), Ling AV(3), Devlin AS(4), Varma Y(4), Fischbach MA(4), Biddinger SB(3),
Dutton RJ(2), Turnbaugh PJ(2).
(1)1] FAS Center for Systems Biology, Harvard University, Cambridge,
Massachusetts 02138, USA  Society of Fellows, Harvard University, Cambridge,
Massachusetts 02138, USA  Molecular Genetics & Microbiology and Institute for
Genome Sciences & Policy, Duke University, Durham, North Carolina 27708, USA.
(2)FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts
02138, USA. (3)Division of Endocrinology, Children's Hospital Boston, Harvard
Medical School, Boston, Massachusetts 02115, USA. (4)Department of Bioengineering
& Therapeutic Sciences and the California Institute for Quantitative Biosciences,
University of California, San Francisco, San Francisco, California 94158, USA.
Nat Biotechnol. 2014 Mar;32(3):243-5.
Long-term dietary intake influences the structure and activity of the trillions
of microorganisms residing in the human gut, but it remains unclear how rapidly
and reproducibly the human gut microbiome responds to short-term macronutrient
change. Here we show that the short-term consumption of diets composed entirely
of animal or plant products alters microbial community structure and overwhelms
inter-individual differences in microbial gene expression. The animal-based diet
increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and
Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant
polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii).
Microbial activity mirrored differences between herbivorous and carnivorous
mammals, reflecting trade-offs between carbohydrate and protein fermentation.
Foodborne microbes from both diets transiently colonized the gut, including
bacteria, fungi and even viruses. Finally, increases in the abundance and
activity of Bilophila wadsworthia on the animal-based diet support a link between
dietary fat, bile acids and the outgrowth of microorganisms capable of triggering
inflammatory bowel disease. In concert, these results demonstrate that the gut
microbiome can rapidly respond to altered diet, potentially facilitating the
diversity of human dietary lifestyles.
PMID: 24336217 [PubMed - indexed for MEDLINE]
163. J Appl Genet. 2014 Feb;55(1):145-54. doi: 10.1007/s13353-013-0179-4. Epub 2013
Taxonomic and gene-centric metagenomics of the fecal microbiome of low and high
feed conversion ratio (FCR) broilers.
Singh KM(1), Shah TM, Reddy B, Deshpande S, Rank DN, Joshi CG.
(1)Department of Animal Biotechnology, Anand Agriculture University, Anand,
388001, India, firstname.lastname@example.org.
Individual weight gain in broiler growers appears to vary, which may in part be
due to variation in their gut microbiota. In this paper we analyse the fecal
microbiota of low and high feed conversion ratio (FCR) broilers. After shotgun
sequencing of the fecal microbiome, we used the SEED database to identify the
microbial diversity and metabolic potential in low and high FCR birds. The
domain-level breakdown of our samples was bacteria (>95 %), eukaryotes (>2 %),
archaea (>0.2 %), and viruses (>0.2 %). At the phylum level, Proteobacteria
(78.83 % in low and 52.04 % in high FCR), Firmicutes (11.97 % in low and 27.53 %
in high FCR) and Bacteroidetes (7.10 % in low FCR and 17.53 % in high FCR)
predominated in the fecal microbial community. Poultry fecal metagenomes revealed
the sequences related to 33 genera in both low and high FCR with significantly
different proportion. Functional analysis revealed that genes for the metabolism
of carbohydrates, amino acids and derivatives and protein metabolism were most
abundant in SEED subsystem in both samples. Genes associated with stress,
virulence, cell wall and cell capsule were also abundant. Indeed, genes
associated with sulphur assimilation, flagellum and flagellar motility were over
represented in low FCR birds. This information could help in developing
strategies to improve feed efficiency and feed formulation for broiler chickens.
PMID: 24136777 [PubMed - indexed for MEDLINE]
164. Schizophr Bull. 2015 Sep;41(5):1153-61. doi: 10.1093/schbul/sbu197. Epub 2015 Feb
Metagenomic Sequencing Indicates That the Oropharyngeal Phageome of Individuals
With Schizophrenia Differs From That of Controls.
Yolken RH(1), Severance EG(2), Sabunciyan S(2), Gressitt KL(2), Chen O(2),
Stallings C(2), Origoni A(3), Katsafanas E(3), Schweinfurth LA(3), Savage CL(3),
Banis M(3), Khushalani S(3), Dickerson FB(3).
(1)Stanley Laboratory of Developmental Neurovirology, Department of Pediatrics,
Johns Hopkins School of Medicine, Baltimore, MD; email@example.com. (2)Stanley
Laboratory of Developmental Neurovirology, Department of Pediatrics, Johns
Hopkins School of Medicine, Baltimore, MD; (3)Stanley Research Program, Sheppard
Pratt Health System, Baltimore, MD.
Mucosal sites such as the oropharynx contain a wide range of microorganisms,
collectively designated as the microbiome. The microbiome can affect behavior
through a number of neurobiological and immunological mechanisms. Most previous
studies have focused on the bacterial components of the microbiome. However, the
microbiome also includes viruses such as bacteriophages, which are viruses that
infect bacteria and alter their metabolism and replication. We employed
metagenomic analysis to characterize bacteriophage genomes in the oral pharynx of
41 individuals with schizophrenia and 33 control individuals without a
psychiatric disorder. This analysis was performed by the generation of more than
100,000,000 sequence reads from each sample and the mapping of these reads to
databases. We identified 79 distinct bacteriophage sequences in the oropharyngeal
samples. Of these, one bacteriophage genome, Lactobacillus phage phiadh, was
found to be significantly different in individuals with schizophrenia (P <
.00037, q < 0.03 adjusted for multiple comparisons). The differential levels of
Lactobacillus phage phiadh remained significant when controlling for age, gender,
race, socioeconomic status, or cigarette smoking (P < .006). Within the group of
individuals with schizophrenia, the level of Lactobacillus phage phiadh
correlated with the prevalence of immunological disorders as well as with the
administration of valproate, which has been shown in animal models to alter the
microbiome. The bacteriophage composition of the oropharynx in individuals with
schizophrenia differs from that of controls. The biological consequences of this
difference and the potential effects of altering bacteriophage levels through
therapeutic interventions are worthy of further investigation.
© The Author 2015. Published by Oxford University Press on behalf of the Maryland
Psychiatric Research Center. All rights reserved. For permissions, please email:
PMID: 25666826 [PubMed - indexed for MEDLINE]
165. J Antimicrob Chemother. 2014 Oct;69(10):2878-80. doi: 10.1093/jac/dku201. Epub
2014 Jun 12.
An emerging understanding of the Janus face of the human microbiome: enhancement
versus impairment of cancer therapy.
Vande Voorde J(1), Balzarini J(2), Liekens S(1).
(1)Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, blok
x-bus 1030, B-3000 Leuven, Belgium. (2)Rega Institute for Medical Research, KU
Leuven, Minderbroedersstraat 10, blok x-bus 1030, B-3000 Leuven, Belgium
PMID: 24925896 [PubMed - indexed for MEDLINE]
166. Curr Opin Pediatr. 2015 Aug;27(4):496-501. doi: 10.1097/MOP.0000000000000234.
Influence of the human intestinal microbiome on obesity and metabolic
Tilg H(1), Adolph TE.
(1)Department of Internal Medicine I, Gastroenterology, Endocrinology &
Metabolism, Medical University Innsbruck, Innsbruck, Austria.
PURPOSE OF REVIEW: Recent studies have suggested that there may be a strong link
between the gut microbiota, energy extraction and body metabolism.
RECENT FINDINGS: Evidence is accumulating that the intestinal microbiota, in
addition to other major factors such as diet and host genetics, contributes to
obesity, metabolic dysfunction and diabetes. Both preclinical experimental and
human studies have shown that obesity and metabolic dysfunction are characterized
by a profound dysbiosis. Several human metagenome-wide association studies have
demonstrated highly significant correlations of certain members of intestinal
microbiota with obesity and type 2 diabetes. In addition dietary factors that
substantially affect microbial composition, microbiota disruption, and the
consequence of early-life antibiotic use, may contribute to childhood obesity and
metabolic dysfunction. Further evidence for an association between microbiota and
metabolic dysfunction has been derived from studies in pregnancy demonstrating
that major gut microbial shifts occur during pregnancy thereby affecting host
metabolism. In particular, the high rate of obesity following caesarean section
could be partially explained by functional alterations in the intestinal
SUMMARY: Obesity and associated metabolic dysfunction emerge from disturbed
interactions between the intestinal microbiota, dietary changes and host immune
functions. A better understanding of this relationship might lead to better
therapies for human metabolic and inflammatory diseases in the future.
PMID: 26087428 [PubMed - indexed for MEDLINE]
167. APMIS. 2015 May;123(5):427-32. doi: 10.1111/apm.12363. Epub 2015 Apr 6.
Analysis of microbiota in stable patients with chronic obstructive pulmonary
Aguirre E(1), Galiana A, Mira A, Guardiola R, Sánchez-Guillén L, Garcia-Pachon E,
Santibañez M, Royo G, Rodríguez JC.
(1)Section of Microbiology, Hospital General Universitario de Elche, Alicante,
To identify the bacterial diversity (microbiota) in expectorated sputum, a
pyrosequencing method that investigates complex microbial communities of
expectorated sputum was done in 19 stable chronic obstructive pulmonary disease
patients (mean (SD) FEV1: 47 (18%) of predicted value). Using conventional
culture, 3 phyla and 20 bacterial genera were identified, whereas the
pyrosequencing approach detected 9 phyla and 43 genera (p < 0.001). In sputum the
prevalent genera with pyrosequencing approach were Streptococcus, Actinomyces,
Neisseria, Haemophilus, Rothia, Fusobacterium, Gemella, Granulicatella,
Porphyromonas, Prevotella and Veillonella. Enterobacteriaceae, detected
frequently in conventional culture, were not significantly detected with
pyrosequencing methods. In addition, we found that important pathogens such as
Haemophilus and Moraxella were detected more frequently with the new genetic
procedures. The presence of Enterobacteriaceae is probably overestimated with
conventional culture, whereas other difficult cultivable pathogens are
underestimated. These studies open a new perspective for evaluating the role of
bacterial colonization in chronic obstructive pulmonary disease pathogenesis and
© 2015 APMIS. Published by John Wiley & Sons Ltd.
PMID: 25858184 [PubMed - indexed for MEDLINE]
168. Am J Clin Nutr. 2015 Jan;101(1):55-64. doi: 10.3945/ajcn.114.092064. Epub 2014
Fiber supplementation influences phylogenetic structure and functional capacity
of the human intestinal microbiome: follow-up of a randomized controlled trial.
Holscher HD(1), Caporaso JG(1), Hooda S(1), Brulc JM(1), Fahey GC Jr(1), Swanson
(1)From the Department of Animal Sciences and Division of Nutritional Sciences,
University of Illinois, Urbana, IL (HDH, SH, GCF, and KSS); the Department of
Biological Sciences and Computer Sciences, Northern Arizona University,
Flagstaff, AZ (JGC); and General Mills Inc., Bell Institute of Health and
Nutrition, Minneapolis, MN (JMB).
Am J Clin Nutr. 2015 Jan;101(1):1-2.
BACKGROUND: In our published randomized, double-blind, placebo-controlled,
3-period crossover trial, healthy adult men (n = 21) consumed bars containing no
supplemental fiber (placebo; NFC), polydextrose (21 g/d), and soluble corn fiber
(SCF; 21 g/d) for 21 d each. Fecal specimens were collected between days 16 and
21 for fermentative end-product analysis and 16S ribosomal RNA bacterial gene
amplification for bacterial taxa identification. Fiber supplementation decreased
fecal putrefaction compounds and shifted abundances of several bacterial taxa.
OBJECTIVE: The objective was to perform whole-genome shotgun 454 pyrosequencing
on the same fecal specimens collected in that clinical trial to obtain
comprehensive fecal bacterial genome sequencing coverage and explore the full
range of bacterial genetic information in the fecal microbiome, thereby using a
systematic approach to study the impact of dietary fiber supplementation on fecal
metabolites, bacterial taxa, and bacterial metagenomes.
DESIGN: Fecal samples were subjected to whole-genome shotgun 454 pyrosequencing
to identify both fecal bacterial populations present and their functional genetic
RESULTS: Whole-genome shotgun sequencing results revealed that fiber consumption
shifted the Bacteroidetes:Firmicutes ratio, increasing the relative abundance of
Bacteroidetes 12 ± 2% and 13 ± 2% with polydextrose and SCF, respectively,
compared with NFC. Bivariate correlations showed a positive correlation between
the Bacteroidetes:Firmicutes ratio and total dietary fiber intake but not body
mass index. Principal coordinates analysis of Bray-Curtis distances indicated
that bacterial gene composition was more similar in participants consuming fibers
(polydextrose and SCF combined) in comparison with NFC. Shifts in bacterial gene
abundances after polydextrose and SCF supplementation included genes associated
with carbohydrate, amino acid, and lipid metabolism, as well as metabolism of
cofactors and vitamins.
CONCLUSION: This study conveys novel information about the impact of dietary
fiber supplementation on the phylogenetic structure and functional capacity of
the fecal microbiome of healthy adults.
© 2015 American Society for Nutrition.
PMID: 25527750 [PubMed - indexed for MEDLINE]
169. Reprod Sci. 2014 Jan;21(1):32-40. doi: 10.1177/1933719113488838. Epub 2013 May
Diversity of the vaginal microbiome correlates with preterm birth.
Hyman RW(1), Fukushima M, Jiang H, Fung E, Rand L, Johnson B, Vo KC, Caughey AB,
Hilton JF, Davis RW, Giudice LC.
(1)1Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA.
Reproductive tract infection is a major initiator of preterm birth (PTB). The
objective of this prospective cohort study of 88 participants was to determine
whether PTB correlates with the vaginal microbiome during pregnancy. Total DNA
was purified from posterior vaginal fornix swabs during gestation. The 16S
ribosomal RNA gene was amplified using polymerase chain reaction primers,
followed by chain-termination sequencing. Bacteria were identified by comparing
contig consensus sequences with the Ribosomal Database Project. Dichotomous
responses were summarized via proportions and continuous variables via means ±
standard deviation. Mean Shannon Diversity index differed by Welch t test (P =
.00016) between caucasians with PTB and term gestation. Species diversity was
greatest among African Americans (P = .0045). Change in microbiome/Lactobacillus
content and presence of putative novel/noxious bacteria did not correlate with
PTB. We conclude that uncultured vaginal bacteria play an important role in PTB
and race/ethnicity and sampling location are important determinants of the
PMID: 23715799 [PubMed - indexed for MEDLINE]
170. Gut Microbes. 2015;6(3):161-72. doi: 10.1080/19490976.2015.1039223.
Gut microbiome compositional and functional differences between tumor and
non-tumor adjacent tissues from cohorts from the US and Spain.
Allali I(1), Delgado S, Marron PI, Astudillo A, Yeh JJ, Ghazal H, Amzazi S, Keku
T, Azcarate-Peril MA.
(1)a Department of Cell Biology and Physiology, and Microbiome Core Facility;
University of North Carolina School of Medicine ; Chapel Hill , NC , USA.
Colorectal cancer (CRC) is the third most common cancer in the world and the
second leading cause of cancer deaths in the US and Spain. The molecular
mechanisms involved in the etiology of CRC are not yet elucidated due in part to
the complexity of the human gut microbiota. In this study, we compared the
microbiome composition of 90 tumor and matching adjacent tissue (adjacent) from
cohorts from the US and Spain by 16S rRNA amplicon sequencing in order to
determine the impact of the geographic origin on the CRC microbiome. Data showed
a significantly (P < 0.05) higher Phylogenetic Diversity (PD) for the US (PD
Adjacent = 26.3 ± 5.3, PD Tumor = 23.3 ± 6.2) compared to the Spanish cohort (PD
Adjacent = 18.9 ± 5.9, PD Tumor = 18.7 ± 6.6) while no significant differences in
bacterial diversity were observed between tumor and adjacent tissues for
individuals from the same country. Adjacent tissues from the Spanish cohort were
enriched in Firmicutes (SP = 43.9% and US = 22.2%, P = 0.0001) and Actinobacteria
(SP = 1.6% and US = 0.5%, P = 0.0018) compared to US adjacent tissues, while
adjacent tissues from the US had significantly higher abundances of Fusobacteria
(US = 8.1% and SP = 1.5%, P = 0.0023) and Sinergistetes (US = 0.3% and SP = 0.1%,
P = 0.0097). Comparisons between tumor and adjacent tissues in each cohort
identified the genus Eikenella significantly over represented in US tumors (T =
0.024% and A = 0%, P = 0.03), and the genera Fusobacterium (T = 10.4% and A =
1.5%, P = <0.0001), Bulleida (T = 0.36% and A = 0.09%, P = 0.02), Gemella (T =
1.46% and A = 0.19%, P = 0.03), Parvimonas (T = 3.14% and A = 0.86%, P = 0.03),
Campylobacter (T = 0.15% and A = 0.008%, P = 0.047), and Streptococcus (T = 2.84%
and A = 2.19%, P = 0.05) significantly over represented in Spanish tumors.
Predicted metagenome functional content from 16S rRNA surveys showed that
bacterial motility proteins and proteins involved in flagellar assembly were over
represented in adjacent tissues of both cohorts, while pathways involved in fatty
acid biosynthesis, the MAPK signaling pathway, and bacterial toxins were over
represented in tumors. Our study suggests that microbiome compositional and
functional dissimilarities by geographic location should be taken in
consideration when approaching CRC therapeutic options.
PMID: 25875428 [PubMed - indexed for MEDLINE]
171. Microbiome. 2015 Aug 12;3:33. doi: 10.1186/s40168-015-0092-7. eCollection 2015.
Collection media and delayed freezing effects on microbial composition of human
Flores R(1), Shi J(2), Yu G(3), Ma B(4), Ravel J(4), Goedert JJ(3), Sinha R(5).
(1)Nutritional Science Research Group, Division of Cancer Prevention, National
Cancer Institute, National Institutes of Health, 9609 Medical Center Dr.
RM5E554-MSC9788, Bethesda, MD 20892 USA. (2)Biostatistics Branch, Division of
Cancer Epidemiology and Genetics, NCI/NIH, Bethesda, MD USA. (3)Infections and
Immunoepidemiology Branch DCEG/NCI/NIH, Bethesda, MD USA. (4)Institute of Genome
Sciences, University of Maryland School of Medicine, Baltimore, MD USA.
(5)Nutritional Epidemiology Branch, DCEG/NCI/NIH, Bethesda, MD USA.
BACKGROUND: Different bacteria in stool have markedly varied growth and survival
when stored at ambient temperature. It is paramount to develop optimal
biostabilization of stool samples during collection and assess long-term storage
for clinical specimens and epidemiological microbiome studies. We evaluated the
effect of collection media and delayed freezing up to 7 days on microbial
composition. Ten participants collected triplicate stool samples each into no
media as well as RNAlater® with and without kanamycin or ciprofloxacin. For each
set of conditions, triplicate samples were frozen on dry ice immediately (time =
0) or frozen at -80 °C after 3-days and 7-days incubation at 25 °C. Microbiota
metrics were estimated from Illumina MiSeq sequences of 16S rRNA gene fragments
(V3-V4 region). Intraclass correlation coefficients (ICC) across triplicates,
collection media, and incubation time were estimated for taxonomy and alpha and
beta diversity metrics.
RESULTS: RNAlater® alone yielded the highest ICCs for diversity metrics at time =
0 [ICC median 0.935 (range 0.89-0.97)], but ICCs varied greatly (range 0.44-1.0)
for taxa with relative abundances <1%. The 3- and 7-day freezing delays were
generally associated with stable beta diversity for all three media conditions.
Freezing delay caused increased variance for Shannon index (median ICC 0.77) and
especially for observed species abundance (median ICC 0.47). Variance in observed
species abundance and in phylogenetic distance whole tree was similarly increased
with a 7-day delay. Antibiotics did not mitigate variance. No media had inferior
ICCs at time 0 and differed markedly from any media in microbiome composition
(e.g., P =0.01 for relative abundance of Bacteroidetes).
CONCLUSION: Bacterial community composition was stable for 7 days at room
temperature in RNAlater® alone. RNAlater® provides some stability for beta
diversity analyses, but analyses of rare taxa will be inaccurate if specimens are
not frozen immediately. RNAlater® could be used as collection media with minimal
change in the microbiota composition.
PMID: 26269741 [PubMed - indexed for MEDLINE]
172. ISME J. 2016 Feb;10(2):321-32. doi: 10.1038/ismej.2015.114. Epub 2015 Aug 14.
Prolonged antibiotic treatment induces a diabetogenic intestinal microbiome that
accelerates diabetes in NOD mice.
Brown K(1), Godovannyi A(1), Ma C(2), Zhang Y(3), Ahmadi-Vand Z(1), Dai C(1),
Gorzelak MA(1), Chan Y(1), Chan JM(2), Lochner A(2), Dutz JP(3), Vallance BA(2),
(1)Department of Biology, University of British Columbia Okanagan, Kelowna,
British Columbia, Canada. (2)Department of Paediatrics, Division of
Gastroenterology, Vancouver, British Columbia, Canada. (3)Departments of Medicine
& Dermatology and Skin Science, Child and Family Research Institute and
University of British Columbia, Vancouver, British Columbia, Canada.
Accumulating evidence supports that the intestinal microbiome is involved in Type
1 diabetes (T1D) pathogenesis through the gut-pancreas nexus. Our aim was to
determine whether the intestinal microbiota in the non-obese diabetic (NOD) mouse
model played a role in T1D through the gut. To examine the effect of the
intestinal microbiota on T1D onset, we manipulated gut microbes by: (1) the fecal
transplantation between non-obese diabetic (NOD) and resistant (NOR) mice and (2)
the oral antibiotic and probiotic treatment of NOD mice. We monitored diabetes
onset, quantified CD4+T cells in the Peyer's patches, profiled the microbiome and
measured fecal short-chain fatty acids (SCFA). The gut microbiota from NOD mice
harbored more pathobionts and fewer beneficial microbes in comparison with NOR
mice. Fecal transplantation of NOD microbes induced insulitis in NOR hosts
suggesting that the NOD microbiome is diabetogenic. Moreover, antibiotic exposure
accelerated diabetes onset in NOD mice accompanied by increased T-helper type 1
(Th1) and reduced Th17 cells in the intestinal lymphoid tissues. The diabetogenic
microbiome was characterized by a metagenome altered in several metabolic gene
clusters. Furthermore, diabetes susceptibility correlated with reduced fecal
SCFAs. In an attempt to correct the diabetogenic microbiome, we administered
VLS#3 probiotics to NOD mice but found that VSL#3 colonized the intestine poorly
and did not delay diabetes. We conclude that NOD mice harbor gut microbes that
induce diabetes and that their diabetogenic microbiome can be amplified early in
life through antibiotic exposure. Protective microbes like VSL#3 are insufficient
to overcome the effects of a diabetogenic microbiome.
PMCID: PMC4737925 [Available on 2017-02-01]
PMID: 26274050 [PubMed - in process]
173. Psychoneuroendocrinology. 2016 Jan;63:217-27. doi:
10.1016/j.psyneuen.2015.10.001. Epub 2015 Oct 9.
Structural & functional consequences of chronic psychosocial stress on the
microbiome & host.
Bharwani A(1), Mian MF(2), Foster JA(3), Surette MG(4), Bienenstock J(1),
(1)Department of Pathology & Molecular Medicine, McMaster University, 1280 Main
Street West Hamilton, Ontario L8S 4L8, Canada; McMaster Brain-Body Institute, St.
Joseph's Healthcare, 50 Charlton Avenue East Hamilton, Ontario L8N 4A6, Canada.
(2)McMaster Brain-Body Institute, St. Joseph's Healthcare, 50 Charlton Avenue
East Hamilton, Ontario L8N 4A6, Canada. (3)Department of Psychiatry & Behavioral
Neurosciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S
4L8, Canada; McMaster Brain-Body Institute, St. Joseph's Healthcare, 50 Charlton
Avenue East Hamilton, Ontario L8N 4A6, Canada. (4)Department of Medicine,
McMaster University, 1280 Main Street West Hamilton, Ontario L8S 4K1, Canada;
Farncombe Family Digestive Health Research Institute, 1280 Main Street West,
Hamilton, Ontario L8S 4L8, Canada. (5)Department of Medicine, McMaster
University, 1280 Main Street West Hamilton, Ontario L8S 4K1, Canada; Firestone
Institute for Respiratory Health, St. Joseph's Healthcare, 50 Charlton Avenue
East Hamilton, Ontario L8N 4A6, Canada; McMaster Brain-Body Institute, St.
Joseph's Healthcare, 50 Charlton Avenue East Hamilton, Ontario L8N 4A6, Canada.
Electronic address: firstname.lastname@example.org.
INTRODUCTION: Given the lasting impact of psychological distress on behavior,
along with the role of the microbiome in neurobehavioral development, we sought
to examine the relationship between the microbiota and stress-induced behavioral
METHODS: Male C57BL/6 mice exposed to chronic social defeat were subjected to
behavioral analysis and profiling of the intestinal microbiome. Mice were also
analyzed for phenotypic and functional immune changes. A computational approach
on 16S rRNA marker gene sequences was used to predict functional changes in the
metagenome as a consequence of structural shifts in the microbiota.
RESULTS: Chronic social defeat induced behavioral changes that were associated
with reduced richness and diversity of the gut microbial community, along with
distinct shifts at the level of operational taxonomic units (OTU) across phyla.
The degree of deficits in social, but not exploratory behavior was correlated
with group differences between the microbial community profile. In silico
analysis predicted a shift in the functional profile of the microbiome: defeated
mice exhibited reduced functional diversity and a lower prevalence of pathways
involved in the synthesis and metabolism of neurotransmitter precursors and
short-chain fatty acids. Defeated mice also exhibited sustained alterations in
dendritic cell activation, and transiently elevated levels of IL-10+ T regulatory
cells that were suppressed over time.
CONCLUSIONS: This study indicates that stress-induced disruptions in neurologic
function are associated with altered immunoregulatory responses and complex
OTU-level shifts in the microbiota. It is thus suggested that a dysbiotic state,
along with specific changes in microbial markers, may predict the onset of
adverse neurocognitive deficits commonly observed following exposure to severe
stressors. The data also predict novel pathways that might underlie
microbiota-mediated effects on brain and behavior, thus presenting targets for
investigations into mechanisms and potential therapy.
Copyright © 2015 Elsevier Ltd. All rights reserved.
PMID: 26479188 [PubMed - in process]
174. Diabetologia. 2014 Aug;57(8):1569-77. doi: 10.1007/s00125-014-3274-0. Epub 2014
Aberrant gut microbiota composition at the onset of type 1 diabetes in young
de Goffau MC(1), Fuentes S, van den Bogert B, Honkanen H, de Vos WM, Welling GW,
Hyöty H, Harmsen HJ.
(1)Department of Medical Microbiology, University Medical Center Groningen,
University of Groningen, Hanzeplein 1, HPC EB80, 9713 GZ, Groningen, The
AIMS/HYPOTHESIS: Recent studies indicate that an aberrant gut microbiota is
associated with the development of type 1 diabetes, yet little is known about the
microbiota in children who have diabetes at an early age. To this end, the
microbiota of children aged 1-5 years with new-onset type 1 diabetes was compared
with the microbiota of age-matched healthy controls.
METHODS: A deep global analysis of the gut microbiota composition was established
by phylogenetic microarray analysis using a Human Intestinal Tract Chip
RESULTS: Principal component analyses highlighted the importance of age when
comparing age-matched pairs. In pairs younger than 2.9 years, the combined
abundance of the class Bacilli (notably streptococci) and the phylum
Bacteroidetes was higher in diabetic children, whereas the combined abundance of
members of Clostridium clusters IV and XIVa was higher in the healthy controls.
Controls older than 2.9 years were characterised by a higher fraction of
butyrate-producing species within Clostridium clusters IV and XIVa than was seen
in the corresponding diabetic children or in children from the younger age
groups, while the diabetic children older than 2.9 years could be differentiated
by having an increased microbial diversity.
CONCLUSIONS/INTERPRETATION: The results from both age groups suggest that
non-diabetic children have a more balanced microbiota in which butyrate-producing
species appear to hold a pivotal position.
PMID: 24930037 [PubMed - indexed for MEDLINE]
175. Semin Reprod Med. 2014 Jan;32(1):5-13. doi: 10.1055/s-0033-1361817. Epub 2014 Jan
Use of whole genome shotgun metagenomics: a practical guide for the
microbiome-minded physician scientist.
Ma J(1), Prince A(1), Aagaard KM(1).
(1)Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology,
Baylor College of Medicine.
Whole genome shotgun sequencing (WGS) has been increasingly recognized as the
most comprehensive and robust approach for metagenomics research. When compared
with 16S-based metagenomics, it offers the advantage of identification of species
level taxonomy and the estimation of metabolic pathway activities from human and
environmental samples. Several large-scale metagenomic projects have been
recently conducted or are currently underway utilizing WGS. With the generation
of vast amounts of data, the bioinformatics and computational analysis of WGS
results become vital for the success of a metagenomics study. However, each step
in the WGS data analysis, including metagenome assembly, gene prediction,
taxonomy identification, function annotation, and pathway analysis, is
complicated by the shear amount of data. Algorithms and tools have been developed
specifically to handle WGS-generated metagenomics data with the hope of reducing
the requirement on computational time and storage space. Here, we present an
overview of the current state of metagenomics through WGS sequencing, challenges
frequently encountered, and up-to-date solutions. Several applications that are
uniquely applicable to microbiome studies in reproductive and perinatal medicine
are also discussed.
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
PMID: 24390915 [PubMed - indexed for MEDLINE]
176. PLoS One. 2015 Jun 15;10(6):e0129055. doi: 10.1371/journal.pone.0129055.
Bacterial Composition of the Human Upper Gastrointestinal Tract Microbiome Is
Dynamic and Associated with Genomic Instability in a Barrett's Esophagus Cohort.
Gall A(1), Fero J(2), McCoy C(3), Claywell BC(3), Sanchez CA(2), Blount PL(4), Li
X(5), Vaughan TL(6), Matsen FA(3), Reid BJ(7), Salama NR(8).
(1)Molecular and Cellular Biology Graduate Program, University of Washington,
Seattle, Washington, United States of America; Human Biology, Fred Hutchinson
Cancer Research Center, Seattle, Washington, United States of America. (2)Human
Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United
States of America. (3)Divisions of Public Health Sciences, Fred Hutchinson Cancer
Research Center, Seattle, Washington, United States of America; Program in
Computational Biology, Fred Hutchinson Cancer Research Center, Seattle,
Washington, United States of America. (4)Divisions of Public Health Sciences,
Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of
America; Department of Medicine, University of Washington School of Medicine,
Seattle, Washington, United States of America. (5)Human Biology, Fred Hutchinson
Cancer Research Center, Seattle, Washington, United States of America; Divisions
of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle,
Washington, United States of America. (6)Divisions of Public Health Sciences,
Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of
America; Department of Epidemiology, University of Washington, Seattle,
Washington, United States of America. (7)Human Biology, Fred Hutchinson Cancer
Research Center, Seattle, Washington, United States of America; Divisions of
Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle,
Washington, United States of America; Department of Medicine, University of
Washington School of Medicine, Seattle, Washington, United States of America;
Department of Genome Sciences, University of Washington, Seattle, Washington,
United States of America. (8)Human Biology, Fred Hutchinson Cancer Research
Center, Seattle, Washington, United States of America; Department of
Microbiology, University of Washington School of Medicine, Seattle, Washington,
United States of America.
BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) has increased nearly
five-fold over the last four decades in the United States. Barrett's esophagus,
the replacement of the normal squamous epithelial lining with a mucus-secreting
columnar epithelium, is the only known precursor to EAC. Like other parts of the
gastrointestinal (GI) tract, the esophagus hosts a variety of bacteria and
comparisons among published studies suggest bacterial communities in the stomach
and esophagus differ. Chronic infection with Helicobacter pylori in the stomach
has been inversely associated with development of EAC, but the mechanisms
underlying this association remain unclear.
METHODOLOGY: The bacterial composition in the upper GI tract was characterized in
a subset of participants (n=12) of the Seattle Barrett's Esophagus Research
cohort using broad-range 16S PCR and pyrosequencing of biopsy and brush samples
collected from squamous esophagus, Barrett's esophagus, stomach corpus and
stomach antrum. Three of the individuals were sampled at two separate time
points. Prevalence of H. pylori infection and subsequent development of
aneuploidy (n=339) and EAC (n=433) was examined in a larger subset of this
RESULTS/SIGNIFICANCE: Within individuals, bacterial communities of the stomach
and esophagus showed overlapping community membership. Despite closer proximity,
the stomach antrum and corpus communities were less similar than the antrum and
esophageal samples. Re-sampling of study participants revealed similar upper GI
community membership in two of three cases. In this Barrett's esophagus cohort,
Streptococcus and Prevotella species dominate the upper GI and the ratio of these
two species is associated with waist-to-hip ratio and hiatal hernia length, two
known EAC risk factors in Barrett's esophagus. H. pylori-positive individuals had
a significantly decreased incidence of aneuploidy and a non-significant trend
toward lower incidence of EAC.
PMID: 26076489 [PubMed - indexed for MEDLINE]
177. PLoS One. 2015 Feb 25;10(2):e0118068. doi: 10.1371/journal.pone.0118068.
Biotic stress shifted structure and abundance of Enterobacteriaceae in the
Erlacher A(1), Cardinale M(1), Grube M(2), Berg G(3).
(1)Institute of Environmental Biotechnology, Graz University of Technology,
Petersgasse 12, 8010, Graz, Austria; Institute of Plant Sciences, University of
Graz, Holteigasse 6, 8010, Graz, Austria. (2)Institute of Plant Sciences,
University of Graz, Holteigasse 6, 8010, Graz, Austria. (3)Institute of
Environmental Biotechnology, Graz University of Technology, Petersgasse 12, 8010,
Lettuce cultivars are not only amongst the most popular vegetables eaten raw,
they are also involved in severe pathogen outbreaks world-wide. While outbreaks
caused by Enterobacteriaceae species are well-studied, less is known about their
occurrence in natural environments as well as the impact of biotic stress. Here,
we studied the ecology of the human health-relevant bacterial family
Enterobacteriaceae and assessed the impact of biotic disturbances by a soil-borne
phytopathogenic fungus and Gastropoda on their structure and abundance in
mesocosm and pot experiments. Using a polyphasic approach including network
analyses of 16S rRNA gene amplicon libraries, quantitative PCR and complementary
fluorescence in situ hybridization (FISH) microscopy we found substantial yet
divergent Enterobacteriaceae communities. A similar spectrum of 14 genera was
identified from rhizo- and phyllospheres but the abundance of Enterobacteriaceae
was on average 3fold higher in phyllosphere samples. Both stress factors shifted
the bacterial community of the leaf habitat, characterized by increases of
species abundance and diversity. For the rhizosphere, we observed significant
structural shifts of Enterobacteriaceae communities but also a high degree of
resilience. These results could be confirmed by FISH microscopy but it was
difficult to visualize phyllosphere communities. Additional inoculation
experiments with Escherichia coli as model revealed their presence below the wax
layer as well as in the endosphere of leaves. The observed presence influenced by
stress factors and the endophytic life style of Enterobacteriaceae on lettuce can
be an important aspect in relation to human health.
PMID: 25714833 [PubMed - indexed for MEDLINE]
178. Microb Biotechnol. 2015 Jan;8(1):5-7.
Beyond borders: investigating microbiome interactivity and diversity for advanced
PMID: 25627938 [PubMed - indexed for MEDLINE]
179. Helicobacter. 2016 Mar 18. doi: 10.1111/hel.12306. [Epub ahead of print]
Changes in the Functional Potential of the Gut Microbiome Following Probiotic
Supplementation during Helicobacter Pylori Treatment.
Oh B(1), Kim JW(2), Kim BS(3).
(1)Department of Family Medicine, Seoul National University Boramae Hospital, 20
Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, Republic of Korea. (2)Department of
internal Medicine, Seoul National University Boramae Hospital, 20 Boramae-ro
5-gil, Dongjak-gu, Seoul, 07061, Republic of Korea. (3)Department of Life
Science, Hallym University, Chuncheon, Gangwon-do, 200-702, Republic of Korea.
BACKGROUND: Probiotic supplementation is utilized to alleviate the side effects
associated with antibiotic therapy for Helicobacter pylori infection. Several
studies have described the effects of administration of probiotics on the gut
microbiota during antibiotic therapy. However, most of these studies have focused
on specific bacteria, thereby providing limited information on the functional
roles of the altered microbiota. Therefore, we examined the impact of probiotic
supplementation on the structure and functional dynamics of the gut microbiota
during H. pylori eradication, using whole-metagenomic sequence analysis.
METHODS: Subjects were divided into two groups: the antibiotics group, which
received only antibiotics, and the probiotics group, which received antibiotics
with probiotic supplementation. The structural and functional profiles of gut
microbiota was analyzed using metagenomic DNA extracted from the feces during
treatment by Illumina MiSeq system.
RESULTS: The overall alterations in microbiota, as revealed by whole metagenome
sequencing, were similar with results from our previous 16S rRNA gene-based
analysis. The proportional shift in functional gene families was greater in the
antibiotics group than in the probiotics group. In particular, the proportion of
genes related to selenocompound metabolism was reduced in the probiotics group,
whereas genes associated with the metabolism of nucleotide sugars were increased.
CONCLUSION: The functional alterations of gut microbiota may link to the
reduction in intestinal irritation and maintenance of bacterial diversity
observed following probiotic supplementation with antibiotic therapy. The
potential beneficial roles of altered gut microbiota following probiotic
supplementation are expected a reduction in side effects such as intestinal
irritation and antibiotics resistance.
© 2016 John Wiley & Sons Ltd.
PMID: 26991862 [PubMed - as supplied by publisher]
180. PLoS One. 2015 Sep 10;10(9):e0137784. doi: 10.1371/journal.pone.0137784.
A Metagenomic Investigation of the Duodenal Microbiota Reveals Links with
Angelakis E(1), Armougom F(1), Carrière F(2), Bachar D(1), Laugier R(3), Lagier
JC(1), Robert C(1), Michelle C(1), Henrissat B(4), Raoult D(1).
(1)URMITE CNRS-IRD 198 UMR 6236, Aix Marseille Université, Faculté de Médecine,
27 Bd Jean Moulin, 13385, Marseille, France. (2)CNRS, Aix Marseille Université,
UMR7282 Enzymology at Interfaces and Physiology of Lipolysis, 13009, Marseille,
France. (3)Hepato-gastroenterology Department, Hôpital de la Timone, Marseille,
France. (4)Architecture et Fonction des Macromolécules Biologiques, Centre
National de la Recherche Scientifique, Aix-Marseille Université, 13288,
Marseille, France; Department of Biological Sciences, King Abdulaziz University,
Jeddah, Saudi Arabia.
BACKGROUND: Few studies have tested the small intestine microbiota in humans,
where most nutrient digestion and absorption occur. Here, our objective was to
examine the duodenal microbiota between obese and normal volunteers using
METHODOLOGY/PRINCIPAL FINDINGS: We tested duodenal samples from five obese and
five normal volunteers using 16S rDNA V6 pyrosequencing and Illumina MiSeq deep
sequencing. The predominant phyla of the duodenal microbiota were Firmicutes and
Actinobacteria, whereas Bacteroidetes were absent. Obese individuals had a
significant increase in anaerobic genera (p < 0.001) and a higher abundance of
genes encoding Acyl-CoA dehydrogenase (p = 0.0018) compared to the control group.
Obese individuals also had a reduced abundance of genes encoding sucrose
phosphorylase (p = 0.015) and 1,4-alpha-glucan branching enzyme (p = 0.05).
Normal weight people had significantly increased FabK (p = 0.027), and the
glycerophospholipid metabolism pathway revealed the presence of phospholipase A1
only in the control group (p = 0.05).
CONCLUSIONS/SIGNIFICANCE: The duodenal microbiota of obese individuals exhibit
alterations in the fatty acid and sucrose breakdown pathways, probably induced by
PMID: 26356733 [PubMed - indexed for MEDLINE]
Gigascience. 2016 Aug 2;5(1):34. doi: 10.1186/s13742-016-0140-7.
Li C1,2, Chng KR1, Boey EJ1, Ng AH1, Wilm A1, Nagarajan N3,4.
Nanopore sequencing provides a rapid, cheap and portable real-time sequencing platform with the potential to revolutionize genomics. However, several applications are limited by relatively high single-read error rates (>10 %), including RNA-seq, haplotype sequencing and 16S sequencing.
We developed the Intramolecular-ligated Nanopore Consensus Sequencing (INC-Seq) as a strategy for obtaining long and accurate nanopore reads, starting with low input DNA. Applying INC-Seq for 16S rRNA-based bacterial profiling generated full-length amplicon sequences with a median accuracy >97 %.
INC-Seq reads enabled accurate species-level classification, identification of species at 0.1 % abundance and robust quantification of relative abundances, providing a cheap and effective approach for pathogen detection and microbiome profiling on the MinION system.
Barcode sequencing; Consensus algorithms; Nanopore sequencing; Rolling circle amplification
PMID: 27485345 PMCID: PMC4970289 DOI: 10.1186/s13742-016-0140-7
[PubMed - in process] Free PMC Article
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Select item 27482928
ISME J. 2016 Aug 2. doi: 10.1038/ismej.2016.108. [Epub ahead of print]
Yan Y1,2, Kuramae EE1, de Hollander M1, Klinkhamer PG2, van Veen JA1,2.
We studied the impact of community diversity on the selection of bacterial communities in the rhizosphere by comparing the composition and the functional traits of these communities in soil and rhizosphere. Differences in diversity were established by inoculating into sterilized soils diluted suspensions of the same soil. We used 16S ribosomal RNA amplicon sequencing to determine the taxonomical structure of the bacterial communities and a shotgun metagenomics approach to investigate the potential functional diversity of the communities. By comparing the bacterial communities in soil and rhizosphere, the selective power of the plant was observed both at the taxonomic and functional level, although the diversity indices of soil and rhizosphere samples showed a highly variable, irregular pattern. Lesser variation, that is, more homogenization, was found for both the taxonomic structure and the functional profile of the rhizosphere communities as compared to the communities of the bulk soil. Network analysis revealed stronger interactions among bacterial operational taxonomic units in the rhizosphere than in the soil. The enrichment processes in the rhizosphere selected microbes with particular functional genes related to transporters, the Embden-Meyerhof-Parnas pathway and hydrogen metabolism. This selection was not random across bacteria with these functional traits, but it was species specific. Overall, this suggests that functional traits are a key to the assembly of bacterial rhizosphere communities.The ISME Journal advance online publication, 2 August 2016; doi:10.1038/ismej.2016.108.
PMID: 27482928 DOI: 10.1038/ismej.2016.108
[PubMed - as supplied by publisher]
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Select item 27482924
ISME J. 2016 Aug 2. doi: 10.1038/ismej.2016.98. [Epub ahead of print]
Klümper U1, Dechesne A1, Riber L2, Brandt KK3, Gülay A1, Sørensen SJ2, Smets BF1.
The environmental stimulants and inhibitors of conjugal plasmid transfer in microbial communities are poorly understood. Specifically, it is not known whether exposure to stressors may cause a community to alter its plasmid uptake ability. We assessed whether metals (Cu, Cd, Ni, Zn) and one metalloid (As), at concentrations causing partial growth inhibition, modulate community permissiveness (that is, uptake ability) against a broad-host-range IncP-type plasmid (pKJK5). Cells were extracted from an agricultural soil as recipient community and a cultivation-minimal filter mating assay was conducted with an exogenous E. coli donor strain. The donor hosted a gfp-tagged pKJK5 derivative from which conjugation events could be microscopically quantified and transconjugants isolated and phylogenetically described at high resolution via FACS and 16S rRNA amplicon sequencing. Metal stress consistently decreased plasmid transfer frequencies to the community, while the transconjugal pool richness remained unaffected with OTUs belonging to 12 bacterial phyla. The taxonomic composition of the transconjugal pools was distinct from their respective recipient communities and clustered dependent on the stress type and dose. However, for certain OTUs, stress increased or decreased permissiveness by more than 1000-fold and this response was typically correlated across different metals and doses. The response to some stresses was, in addition, phylogenetically conserved. This is the first demonstration that community permissiveness is sensitive to metal(loid) stress in a manner that is both partially consistent across stressors and phylogenetically conserved.The ISME Journal advance online publication, 2 August 2016; doi:10.1038/ismej.2016.98.
PMID: 27482924 DOI: 10.1038/ismej.2016.98
[PubMed - as supplied by publisher]
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Select item 27477857
Environ Sci Technol. 2016 Sep 6;50(17):9279-88. doi: 10.1021/acs.est.6b02007. Epub 2016 Aug 18.
Torresi E1,2, Fowler SJ1, Polesel F1, Bester K3, Andersen HR1, Smets BF1, Plósz BG1, Christensson M2.
In biofilm systems for wastewater treatment (e.g., moving bed biofilms reactors-MBBRs) biofilm thickness is typically not under direct control. Nevertheless, biofilm thickness is likely to have a profound effect on the microbial diversity and activity, as a result of diffusion limitation and thus substrate penetration in the biofilm. In this study, we investigated the impact of biofilm thickness on nitrification and on the removal of more than 20 organic micropollutants in laboratory-scale nitrifying MBBRs. We used novel carriers (Z-carriers, AnoxKaldnes) that allowed controlling biofilm thickness at 50, 200, 300, 400, and 500 μm. The impact of biofilm thickness on microbial community was assessed via 16S rRNA gene amplicon sequencing and ammonia monooxygenase (amoA) abundance quantification through quantitative PCR (qPCR). Results from batch experiments and microbial analysis showed that (i) the thickest biofilm (500 μm) presented the highest specific biotransformation rate constants (kbio, L g(-1) d(-1)) for 14 out of 22 micropollutants; (ii) biofilm thickness positively associated with biodiversity, which was suggested as the main factor for the observed enhancement of kbio; (iii) the thinnest biofilm (50 μm) exhibited the highest nitrification rate (gN d(-1) g(-1)), amoA gene abundance and kbio values for some of the most recalcitrant micropollutants (i.e., diclofenac and targeted sulfonamides). Although thin biofilms favored nitrification activity and the removal of some micropollutants, treatment systems based on thicker biofilms should be considered to enhance the elimination of a broad spectrum of micropollutants.
PMID: 27477857 DOI: 10.1021/acs.est.6b02007
[PubMed - in process]