A signature of Prevotella copri and Faecalibacterium prausnitzii depletion, and a link with bacterial glutamate degradation in the Kenyan colorectal cancer patients

Sarah Obuya; Amr Elkholy; Nagavardhini Avuthu; Michael Behring; Prachi Bajpai; Sumit Agarwal; Hyung-Gyoon Kim; Nefertiti El-Nikhely; Pamela Akinyi; James Orwa; Farrukh Afaq; Mohammed Abdalla; Anwar Michael; Mohamed Farouk; Lori Brand Bateman; Mona Fouad; Mansoor Saleh; Chittibabu Guda; Upender Manne; Waleed Arafat

doi:10.21037/jgo-22-116

A signature of Prevotella copri and Faecalibacterium prausnitzii depletion, and a link with bacterial glutamate degradation in the Kenyan colorectal cancer patients

J Gastrointest Oncol. 2022 Oct;13(5):2282-2292. doi: 10.21037/jgo-22-116.

Authors

Sarah Obuya^#^{1

2}, Amr Elkholy^#^{3

4}, Nagavardhini Avuthu^#⁵, Michael Behring³, Prachi Bajpai³, Sumit Agarwal³, Hyung-Gyoon Kim³, Nefertiti El-Nikhely⁵, Pamela Akinyi⁶, James Orwa⁷, Farrukh Afaq³, Mohammed Abdalla⁵, Anwar Michael², Mohamed Farouk², Lori Brand Bateman^{8

9}, Mona Fouad^{8

9}, Mansoor Saleh¹⁰, Chittibabu Guda⁵, Upender Manne^{3

9}, Waleed Arafat²

Affiliations

¹ Moi Teaching and Referral Hospital, Moi University, Kesses, Kenya.
² Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
³ Department of Pathology, University of Alabama at Birmingham, AL, USA.
⁴ Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt.
⁵ Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
⁶ International Cancer Institute, Eldoret, Kenya.
⁷ Department of Population Health, Aga Khan University, Nairobi, Kenya.
⁸ Division of Preventive Medicine, University of Alabama at Birmingham, AL, USA.
⁹ Department of Hematology-Oncology, Aga Khan University, Nairobi, Kenya.
¹⁰ O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.

^# Contributed equally.

Abstract

Background: Colorectal cancer (CRC) is the fifth most diagnosed cancer in Sub-Saharan Africa. In Kenya, CRC incidence rates tripled from 1997 to 2017. In the Moi Teaching and Referral Hospital, Moi University, there has been an increase in CRC cases, notably for younger patients. A suggested pathobiology for this increase is gut microbiome dysbiosis. Since, for the Kenyan CRC patient population, microbiome studies are rare, there is a need for a better understanding of how microbiome dysbiosis influences CRC epidemiology in Kenya. In this single-center study, the focus was on profiling the gut microbiome of Kenyan CRC patients and healthy volunteers and evaluating associations between microbiome profiles and the age of CRC patients.

Methods: The gut mucosa-associated microbiome of 18 CRC patients and 18 healthy controls were determined by 16S rRNA sequencing and analyzed for alpha and beta diversity, differential abundance, and microbial metabolic profiling.

Results: Alpha diversity metrics showed no significant differences, but beta diversity metrics showed dissimilarities in the microbial communities between CRC patients and healthy controls. The most underrepresented species in the CRC group were Prevotella copri (P. copri) and Faecalibacterium prausnitzii (F. prausnitzii), although Bacteroides fragilis (B. fragilis) and Prevotella nigrescens were overrepresented (linear discriminant analysis, LDA score >2, P<0.05). Also, for CRC patients, significant metagenomic functional alterations were evident in microbial glutamate metabolic pathways (L-glutamate degradation VIII was enriched, and L-glutamate and L-glutamine biosynthesis were diminished) (P<0.05, log2 Fold Change >1). Moreover, the microbiome composition was different for patients under 40 years of age compared to older patients (LDA score >2, P<0.05).

Conclusions: Microbiome and microbial metabolic profiles of CRC patients are different from those of healthy individuals. CRC microbiome dysbiosis, particularly P. copri and F. prausnitzii depletion and glutamate metabolic alterations, are evident in Kenyan CRC patients.

Keywords: Colorectal cancer (CRC); Faecalibacterium prausnitzii; Kenya; Prevotella copri; microbiome.

Abstract

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